Vanilloid receptor ligands and their use in treatments

• US 20030195201A1
• Filed: 12/10/2002
• Published: 10/16/2003
• Est. Priority Date: 12/10/2001
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Chen, Ning, Kelly, Michael G., Wang, Xianghong, Zhu, Jiawang, Bo, Yunxin Y., Liu, Qingyian, Han, Nianhe, Fotsch, Christopher H., Doherty, Elizabeth M., Ognyanov, Vassil I., Chakrabarti, Partha P., Norman, Mark Henry
• Granted Patent: US 7,582,657 B2
• Time in Patent Office: Days
• US Class Current: 514/227.5
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 209/08 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/12 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 209/42 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 209/48 : with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 213/26 : Radicals substituted by halogen atoms or nitro radicals
• CPC Class Codes: C07D 213/643 : 2-Phenoxypyridines; Derivatives thereof
• CPC Class Codes: C07D 213/74 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 215/227 : only one oxygen atom which is attached in position 2
• CPC Class Codes: C07D 215/38 : Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 217/04 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 231/40 : Acylated on said nitrogen atom
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 233/38 : with acyl radicals or hetero atoms directly attached to ring nitrogen atoms
• CPC Class Codes: C07D 237/20 : Nitrogen atoms nitro radicals C07D237/12
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 239/90 : with acyclic radicals attached in position 2 or 3
• CPC Class Codes: C07D 241/42 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 263/56 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
• CPC Class Codes: C07D 265/36 : condensed with one six-membered ring
• CPC Class Codes: C07D 277/62 : Benzothiazoles
• CPC Class Codes: C07D 277/82 : Nitrogen atoms
• CPC Class Codes: C07D 307/79 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 319/20 : with substituents attached to the hetero ring
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

Compounds having the general structure

and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

Claims

1. A compound having the structure:

2. A compound according to claim 1, wherein:

R¹ is

 

or a naphthyl or saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the naphthyl, heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷;

R² is H, hydroxy, halo, C_1-6alkyl substituted by 0, 1 or 2 substituents selected from R¹⁰,

 

or a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷; and

R³ is H or C_1-4alkyl.

3. A compound according to claim 1, wherein R¹ is

4. A compound according to claim 3, wherein R⁷ is independently, at each instance, C_2-9alkyl or C_1-4haloalkyl.

5. A compound according to claim 1, wherein R¹ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷.

6. A compound according to claim 5, wherein R² is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷.

7. A compound according to claim 2, wherein R² is

8. A compound according to claim 7, wherein R² is

9. A compound according to claim 7, wherein R² is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷.

10. A compound according to claim 2, wherein R¹ and R² together are

11. A compound according to claim 2, wherein R¹ and R³ together are

12. A compound according to claim 2, wherein X and R² together are ═

N—

CH═

CH—

, ═

C—

O—

, ═

C—

S—

, or ═

C—

NR^a—

.

13. A compound according to claim 2, wherein:

R⁴ is

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^a—

or —

O—

.

14. A compound according to claim 2, wherein:

R⁴ is

L³ is a 2- or 3-atom, saturated or unsaturated, bridge containing 1, 2 or 3 carbon atoms and 0 or 1 atoms independently selected from O, N and S, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, —

OR^a, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

NR^aR^a, —

C_1-6alkylNR^aR^a, —

C(═

O)OR^a, —

C(═

O)NR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

OC(═

O)C_1-6alkyl, —

NR^aC(═

O)C_1-6alkyl, —

C_1-3alkylOC(═

O)C_1-6alkyl or —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

C_1-6alkylNR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, —

C(═

O)R^c or —

C_1-3alkylR^c;

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^b—

or —

O—

.

15. A compound according to claim 2, wherein:

R⁴ is

L³ is a 2- or 3-atom, saturated or unsaturated, bridge containing 1, 2 or 3 carbon atoms and 0, 1 or 2 atoms independently selected from O, N and S, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, —

OR^a, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

NR^aR^a, —

C_1-6alkylNR^aR^a, —

C(═

O)OR^a, —

C(═

O)NR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

OC(═

O)C_1-6alkyl, —

NR^aC(═

O)C_1-6alkyl, —

C_1-3alkylOC(═

O)C_1-6alkyl or —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

C_1-6alkylNR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, —

C(═

O)R^c or —

C_1-3alkylR^c;

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^b—

or —

O—

.

16. A compound according to claim 2, wherein:

R⁴ is

L³ is a 2- or 3-atom, saturated or unsaturated, bridge containing 1, 2 or 3 carbon atoms and 0, 1 or 2 atoms independently selected from O, N and S, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, —

OR^a, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

NR^aR^a, —

C_1-6alkylNR^aR^a, —

C(═

O)OR^a, —

C(═

O)NR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

OC(═

O)C_1-6alkyl, —

NR^aC(═

O)C_1-6alkyl, —

C_1-3alkylOC(═

O)C_1-6alkyl or —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

C_1-6alkylNR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, —

C(═

O)R^c or —

C_1-3alkylR^c;

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^b—

or —

O—

.

17. A compound according to claim 2, wherein:

R⁴ is

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^a—

or —

O—

.

18. A compound according to claim 2, wherein:

R⁴ is 10-membered bicyclic ring comprising fused 6-membered rings, containing 0, 1, 2, 3 or 4 N atoms with the remainder being carbon atoms, with at least one of the 6-membered rings being aromatic, wherein the carbon atoms are substituted by H, halo, OR^a, NR^aR^a, C_1-6alkyl and C_1-3haloalkyl; and

saturated carbon atoms may be additionally substituted by ═

O.

19. A compound according to claim 2, wherein:

R⁴ is

R¹⁰ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

R¹¹ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylR^c, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

C_1-6alkylNR^aR^a;

R¹² is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

R¹³ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl; and

R¹⁴ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

wherein one of R¹⁰ and R¹² is not H.

20. A compound according to claim 2, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents selected from halo, C_1-4haloalkyl, —

OR^a and —

NR^aR^a.

164. A compound according to claim 1, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:

(2E)-3-[4-(tert-butyl)phenyl]-N-phenylprop-2-enamide,

(2E)-N-(3,4-dimethoxyphenyl)-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(4-hydroxy-3-methoxyphenyl)prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(2-5,6,7,8-tetrahydronaphthyl)prop-2-enamide,

(2E)-N-(2H,3H,4H-benzo[3,4-e]1,4-oxazaperhydroin-6-yl)-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(3-oxo(2H,4H-benzo[3,4-e]1,4-oxazaperhydroin-6-yl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(4-methyl-3-oxo(2H-benzo[3,4-e]1,4-oxazaperhydroin-6-yl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(4-methyl(2H,3H-benzo[3,4-e]1,4-oxazaperhydroin-6-yl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(3-oxo(2H,4H-benzo[e]1,4-oxazaperhydroin-7-yl))prop-2-enamide,

(2E)-N-(2H,3H,4H-benzo[e]1,4-oxazaperhydroin-7-yl)-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(4-methyl-3-oxo(2H-benzo[e]1,4-oxazaperhydroin-7-yl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(4-methyl(2H,3H-benzo[e]1,4-oxazaperhydroin-7-yl))prop-2-enamide, ethyl 6-{(2E)-3-[4-(tert-butyl)phenyl]prop-2-enoyl amino}-2H,3H,4H-benzo[e]1,4-oxazaperhydroine-2-carboxylate,

(2E)-3-[4-(tert-butyl)phenyl]-N-[2-(hydroxymethyl)(2H,3H,4H-benzo[3,4-e]1,4-oxazaperhydroin-6-yl)]prop-2-enamide,

(2E)-N-[(3S)-3-(hydroxymethyl)(2H,3H-benzo[e]1,4-dioxan-6-yl)]-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-N-[(3R)-3-(hydroxymethyl)(2H,3H-benzo[e]1,4-dioxan-6-yl)]-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-N-[(2R)-2-(hydroxymethyl)(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)]-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-N-[(2S)-2-(hydroxymethyl)(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)]-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(7-1,2,3,4-tetrahydroquinolyl)prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(1-methyl(7-1,2,3,4-tetrahydroquinolyl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(2-oxo(6-1,3,4-trihydroquinolyl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(2-oxo(7-1,3,4-trihydroquinolyl))prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(3-hydroxyphenyl)prop-2-enamide, 2-(3-{(2E)-3-[4-(tert-butyl)phenyl]prop-2-enoylamino}phenoxy)acetic acid,

(2E)-3-[4-(tert-butyl)phenyl]-N-[3-(2-hydroxyethoxy)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[3-(2-methoxyethoxy)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-{3-[2-(1,3-dioxobenzo[c]azolin-2-yl)ethoxy]phenyl}prop-2-enamide,

(2E)-N-[3-(2-Aminoethoxy)phenyl]-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-indolin-6-ylprop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(1-methylindolin-6-yl)prop-2-enamide,

(2E)-N-(1-Acetyl-3,3-dimethylindolin-6-yl)-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(1,3,3-trimethylindolin-6-yl)prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(1-methylindol-6-yl)prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(1-methylindol-5-yl)prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(1-methylindolin-5-yl)prop-2-enamide,

(2E)-N-benzoxazol-5-yl-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-N-benzoxazol-6-yl-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-N-benzo[b]furan-5-yl-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-(2,3-dihydrobenzo[b]furan-5-yl)prop-2-enamide,

N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3,3-bis(4-methylphenyl)prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-2-methylprop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-2-ethylprop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-(4-cyclopropylphenyl)prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[6-(tert-butyl)(3-pyridyl)]prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[3-(tert-butyl)phenyl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[2-fluoro-4-(trifluoromethyl)-phenyl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[2,3-difluoro-4-(trifluoromethyl)-phenyl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e],1,4-dioxan-6-yl)-3-[2,4-bis(trifluoromethyl)-phenyl]prop-2-enamide,

(2E)-3-[2-fluoro-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide,

(2E)-3-[2,3-difluoro-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide,

(2E)-3-[2,4-bis(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide,

N-(2H,3H-benzo[e]1,4-dioxan-6-yl)(2Z)-3-[4-(tert-butyl)phenyl]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-4-phenylbut-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-5-methylhex-2-enamide,

N-(2H,3H-benzo[e]1,4-dioxan-6-yl)(2Z)-3-[4-(tert-butyl)phenyl]-3-iodoprop-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-(3-aminophenyl)-3-[4-(tert-butyl)phenyl]prop-2-enamide,

ethyl (4E)-5-(N-(2H,3H-benzo[e]1,4-dioxan-6-yl)carbamoyl)-4-[4-(tert-butyl)phenyl]pent-4-enoate,

3-methoxyphenyl (2E)-3-[4-(tert-butyl)phenyl]prop-2-enoate,

N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)(2Z)-3-[4-(tert-butyl)phenyl]-3-hydroxyprop-2-enamide,

N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)[7-(tert-butyl)(3-isoquinolyl)]-carboxamide,

N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)(2Z)-3-[4-(tert-butyl)phenyl]prop-2-enamide,

N-(2H,3H-benzo[e]1,4-dioxan-6-yl)(2Z)-3-[4-(tert-butyl)phenyl]-3-phenylprop-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-3-phenylprop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[1-(N-methylcarbamoyl)(1H-indazol-6-yl)]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-{4-chloro-3-[(methylamino)carbonylamino]-phenyl}prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-quinoxalin-6-ylprop-2-enamide,

(2E)-N-(1-acetyl(7-1,2,3,4-tetrahydroquinolyl))-3-[4-(tert-butyl)phenyl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[1-(2-methoxyethyl)indol-6-yl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[1-(2-methoxyethyl)indol-5-yl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[1-(2-hydroxyethyl)indol-6-yl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[1-(2-hydroxyethyl)indol-5-yl]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[2-(hydroxymethyl)indol-5-yl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[6-(tert-butyl)-2-methyl(3-pyridyl)]prop-2-enamide,

(2E)-3-[6-(tert-butyl)-2-methyl(3-pyridyl)]-N-indol-6-ylprop-2-enamide,

(2E)-N-benzothiazol-6-yl-3-[6-(tert-butyl)-2-methyl(3-pyridyl)]prop-2-enamide,

(2E)-3-[6-(tert-butyl)-2-methyl (3-pyridyl)]-N-indol-5-ylprop-2-enamide,

(2E)-3-[6-(tert-butyl)-2-methyl(3-pyridyl)]-N-[2-(hydroxymethyl)indol-5-yl]prop-2-enamide,

(2E)-3-[6-(tert-butyl)(3-pyridyl)]-N-[2-(hydroxymethyl)indol-5-yl]prop-2-enamide,

(2E)-3-[6-(tert-butyl)(3-pyridyl)]-N-[1-(2-hydroxyethyl)indol-5-yl]prop-2-enamide,

(2E)-N-indol-6-yl-3-[2-methyl-6-(trifluoromethyl)(3-pyridyl)]prop-2-enamide,

(2E)-N-indol-5-yl-3-[2-methyl-6-(trifluoromethyl)(3-pyridyl)]prop-2-enamide,

(2E)-N-benzothiazol-6-yl-3-[2-methyl-6-(trifluoromethyl)(3-pyridyl)]prop-2-enamide,

(2E)-N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[2-methyl-6-(trifluoromethyl)(3-pyridyl)]prop-2-enamide,

(2E)-3-[4-(tert-butyl)phenyl]-N-[3-(hydroxymethyl)-2-oxo(7-1,3,4-trihydroquinolyl)]prop-2-enamide,

(2E)-N-[3-(hydroxymethyl)(7-1,2,3,4-tetrahydroquinolyl)]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-[3-(hydroxymethyl)-1-methyl (7-1,2,3,4-tetrahydroquinolyl)]-3-[4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-5-(1,3-dioxolan-2-yl)pent-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-4-(3-pyridyl)but-2-enamide,

N-(2H,3H-benzo[e]1,4-dioxan-6-yl)(2Z)-3-[4-(tert-butyl)phenyl]-4-pyrrolidinylbut-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]-6-imidazolylhex-2-enamide,

3-(4-tert-butyl-phenyl)-6-imidazol-1-yl-hex-2-enoic acid benzothiazol-6-ylamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[2-morpholin-4-yl-6-(trifluoromethyl)(3-pyridyl)]prop-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)-2-bromophenyl]prop-2-enamide,

ethyl 2-[(1E)-2-(N-(2H,3H-benzo[e]1,4-dioxan-6-yl)carbamoyl)vinyl]-5-(tert-butyl)benzoate,

(2E)-3-[2-Bromo-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide,

(2E)-N-benzothiazol-6-yl-3-[2-bromo-4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-(2H,3H-benzo[e]1,4-dioxan-6-yl)-3-[2-bromo-4-(trifluoromethyl)-phenyl]prop-2-enamide,

(2E)-N-indol-5-yl-3-[2-(6-methoxy(3-pyridyl))-4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-indol-5-yl-3-[2-(4-pyridyl)-4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-indol-5-yl-3-[2-(3-pyridyl)-4-(trifluoromethyl)phenyl]prop-2-enamide,

tert-butyl 4-{2-[(1E)-2-(N-indol-5-ylcarbamoyl)vinyl]-5-(trifluoromethyl)phenyl}-1,2,5,6-tetrahydropyridinecarboxylate,

(2E)-N-indol-5-yl-3-[2-(1,3-thiazol-2-yl)-4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-N-indol-5-yl-3-[2-(3-pyridylmethyl)-4-(trifluoromethyl)phenyl]prop-2-enamide,

(2E)-3-[2-(3-pyridyl)-4-(trifluoromethyl)phenyl]-N-(7-quinolyl)prop-2-enamide,

(2E)-3-[2-(3-pyridyl)-4-(trifluoromethyl)phenyl]-N-(3-quinolyl)prop-2-enamide,

(2E)-N-indol-6-yl-3-[2-(3-pyridyl)-4-(trifluoromethyl)phenyl]prop-2-enamide, and

N-(2H,3H-benzo[3,4-e]1,4-dioxan-6-yl)-3-[4-(tert-butyl)phenyl]propanamide.

168. A compound according to claim 1, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:

196. A pharmaceutical composition comprising a compound according to any one of claim 1 and a pharmaceutically-acceptable diluent or carrier.

21. A compound having the structure:

22. The compound according to claim 21, wherein R¹⁶ is halo, —

NH₂, —

NHC_1-3alkyl, —

N(C_1-3alkyl)C_1-3alkyl or C_1-3alkyl.

23. The compound according to claim 21, wherein R¹⁰ is independently, at each instance, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d;

or R¹⁰ is a saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2 or 3 atoms selected from N, O and S, wherein the ring is fused with 0 or 1 benzo groups and 0 or 1 saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring containing 1, 2 or 3 atoms selected from N, O and S;

wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groups selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d;

or R¹⁰ is C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d.

24. The compound according to any one of claim 21, wherein R¹ is

25. The compound according to claim 24, wherein R⁷ is C_1-5alkyl, halo or C_1-4haloalkyl.

26. The compound according to claim 21, wherein R¹ is naphthyl substituted by 0, 1, 2 or 3 substituents independently selected from R⁵.

27. The compound according to claim 21, wherein R¹ is R^e substituted by 0, 1, 2 or 3 substituents independently selected from R⁵.

28. The compound according to claim 27, wherein R¹ is R^e substituted by 1, 2 or 3 substituents independently selected from R⁵.

29. The compound according to claim 21, wherein R⁴ is

30. The compound according to claim 29, wherein

R¹⁰ and R¹¹ together are a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^d, —

C_1-6alkyl, —

C_1-6alkylNR^dR^d, —

C_1-3alkylC(═

O)OR^d, —

C_1-3alkylC(═

O)NR^dR^d, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^dC(═

O)C_1-6alkyl, —

C(═

O)R^f or —

C_1-3alkylR^f;

or

R¹¹ and R¹² together are a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^d, —

C_1-6alkyl, —

C_1-6alkylNR^dR^d, —

C_1-3alkylC(═

O)OR^d, —

C_1-3alkylC(═

O)NR^dR^d, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^dC(═

O)C_1-6alkyl, —

C(═

O)R^f or —

C_1-3alkylR^f.

31. The compound according to claim 21, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the heterocycle and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, oxo, —

OR^d, —

S(═

O)_nC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

OC_1-6alkylC(═

O)OR^d, —

NR^dR^d, —

NR^dC_1-4haloalkyl, —

NR^dC_2-6alkylNR^dR^d, —

NR^dC_2-6alkylOR^d, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^dC_1-6alkyl and —

NR^dC(═

O)C_1-6alkyl; and

saturated carbon atoms may be additionally substituted by ═

O; and

any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^d, —

C_1-6alkyl, —

C_1-6alkylNR^dR^d, —

C_1-3alkylC(═

O)OR^d, —

C_1-3alkylC(═

O)NR^dR^d, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^dC(═

O)C_1-6alkyl, —

C(═

O)R^f or —

C_1-3alkylR^f.

32. The compound according to claim 31, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the heterocycle and bridge are substituted by 1, 2 or 3 substituents independently selected from C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, oxo, —

OR^d, —

S(═

O)_nC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

OC_1-6alkylC(═

O)OR^d, —

NR^dR^d, —

NR^dC_1-4haloalkyl, —

NR^dC_2-6alkylNR^dR^d, —

NR^dC_2-6alkylOR^d, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^dC_1-6alkyl and —

NR^dC(═

O)C_1-6alkyl; and

saturated carbon atoms may be additionally substituted by ═

O; and

any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^d, —

C_1-6alkyl, —

C_1-6alkylNR^dR^d, —

C_1-3alkylC(═

O)OR^d, —

C_1-3alkylC(═

O)NR^dR^d, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^dC(═

O)C_1-6alkyl, —

C(═

O)R^f or —

C_1-3alkylR^f.

33. The compound according to claim 21, wherein or R⁴ is 10-membered bicyclic ring comprising fused 6-membered rings, containing 0, 1, 2, 3 or 4 N atoms with the remainder being carbon atoms, with at least one of the 6-membered rings being aromatic, wherein the carbon atoms are substituted by H, halo, OR^d, NR^dR^d, C_1-6alkyl and C_1-3haloalkyl;

and saturated carbon atoms may be additionally substituted by ═

O.

34. The compound according to claim 33, wherein R⁴ is 10-membered bicyclic ring comprising fused 6-membered rings, containing 1, 2, 3 or 4 N atoms with the remainder being carbon atoms, with at least one of the 6-membered rings being aromatic, wherein the carbon atoms are substituted by H, halo, OR^d, NR^dR^d, C_1-6alkyl and C_1-3haloalkyl;

and saturated carbon atoms may be additionally substituted by ═

O.

165. A compound according to claim 21, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:

(4-benzo[1,3]dioxol-5-yl-pyridin-2-yl)-(2,3-dihydro-benzo[1,4]dioxin-6-yl)amine,

(2,3-dihydro-benzo[1,4]dioxin-6-yl)-[4-(4-dimethylamino-phenyl)-pyridin-2-yl]-amine,

(2,3-dihydro-benzo[1,4]dioxin-6-yl)-[4-(4-fluoro-phenyl)-pyridin-2-yl]-amine,

(2,3-dihydro-benzo[1,4]dioxin-6-yl)-[4-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-amine,

(4-benzo[b]thiophen-2-yl-pyridin-2-yl)-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-amine,

1-{4-[2-(2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-pyridin-4-yl]-phenyl}-ethanone,

1-{4-[2-(2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-pyridin-4-yl]-phenyl}-ethanol,

[4-(3,5-bis-trifluoromethyl-phenyl)-pyridin-2-yl]-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-amine,

(2,3-dihydro-benzo[1,4]dioxin-6-yl)-[4-(4-trifluoromethoxy-phenyl)-pyridin-2-yl]-amine, and

quinolin-3-yl-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-amine.

167. A compound according to claim 21, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:

191. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound according to claim 21.

197. A pharmaceutical composition comprising a compound according to any one of claim 21 and a pharmaceutically-acceptable diluent or carrier.

35. A compound having the structure:

36. The compound according to any one of claim 35, wherein Y is NH.

37. The compound according to any one of claim 35, wherein Y is O.

38. The compound according to any one of claim 35, wherein Y is S.

39. The compound according to any one of claim 35, wherein R¹ is

40. The compound according to claim 39, wherein R⁷ is C_1-5alkyl, halo or C_1-4haloalkyl.

41. The compound according to claim 35, wherein R¹ is a naphthyl substituted by 0, 1, 2 or 3 substituents independently selected from R⁵.

42. The compound according to claim 35, wherein R¹ is R^e substituted by 1, 2 or 3 substituents independently selected from R⁵;

43. The compound according to claim 35, wherein R¹⁵ is —

(CH₂)_nphenyl substituted by 0, 1, 2 or 3 substituents independently selected from R¹⁰.

44. The compound according to claim 35, wherein R¹⁵ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R¹⁰.

45. The compound according to claim 35, wherein R¹⁵ is C_1-8alkyl substituted by 0, 1 or 2 substituents selected from R¹⁰.

46. The compound according to claim 35, wherein R¹⁵ is selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d;

or R¹⁰ is a saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2 or 3 atoms selected from N, O and S, wherein the ring is fused with 0 or 1 benzo groups and 0 or 1 saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring containing 1, 2 or 3 atoms selected from N, O and S;

wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 groups selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d;

or R¹⁰ is C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^dR^d, —

C(═

NR^d)NR^dR^d, —

OR^d, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^dR^d, —

OC(═

O)N(R^d)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

SR^d, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^dR^d, —

S(═

O)₂N(R^d)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^d)C(═

O)NR^dR^d, —

NR^dR^d, —

N(R^d)C(═

O)(C_1-8alkyl), —

N(R^d)C(═

O)O(C_1-8alkyl), —

N(R^d)C(═

O)NR^dR^d, —

N(R^d)C(═

NR^d)NR^dR^d, —

N(R^d)S(═

O)₂(C_1-8alkyl), —

N(R^d)S(═

O)₂NR^dR^d, —

NR^dC_2-6alkylNR^dR^d and —

NR^dC_2-6alkylOR^d.

47. The compound according to claim 35, wherein R¹⁶ is, independently, in each instance, halo, —

NH₂, —

NHC_1-3alkyl, —

N(C_1-3alkyl)C_1-3alkyl or C_1-3alkyl.

48. The compound according to claim 35, wherein R⁴ is an unsaturated 6-membered ring containing 0 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

49. The compound according to claim 35, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 1, 2 or 3 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

but in no instance is R⁴ 3,5-ditrifluoromethylphenyl or 3-trifluoromethyl-4-fluorophenyl.

50. The compound according to claim 35, wherein R⁴ is a saturated or unsaturated 6-membered ring containing 0 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

but in no instance is R⁴ 3,5-ditrifluoromethylphenyl or 3-trifluoromethyl-4-fluorophenyl.

51. The compound according to claim 35, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 1, 2 or 3 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

but in no instance is R⁴ 3,5-ditrifluoromethylphenyl or 3-trifluoromethyl-4-fluorophenyl.

52. The compound according to claim 35, wherein R⁹ is H.

53. The compound according to claim 35, wherein R⁹ is independently, at each instance, C_1-8alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^dR^d, —

OC_2-6alkylOR^d, —

NR^dR^d, —

NR^dC_1-4haloalkyl, —

NR^dC_2-6alkylNR^dR^d or —

NR^dC_2-6alkylOR^d, —

CO₂(C_1-6alkyl), —

C(═

O)(C_1-6alkyl), —

C(═

O)NR^dR^d, —

NR^dC(═

O)(C_1-6alkyl), —

NR^dC(═

O)NR^dR^d, —

NR^dCO₂(C_1-6alkyl), —

C_1-8alkylOR^d, —

C_1-6alkylNR^dR^d, —

S(═

O)_n(C_1-6alkyl), —

S(═

O)₂NR^dR^d, —

NR^dS(═

O)₂(C_1-6alkyl) or —

OC(═

O)NR^dR^d.

54. The compound according to claim 35, wherein R⁹ is a —

(CR^qR^q)_ophenyl wherein the phenyl is substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰.

55. The compound according to claim 35, wherein R⁹ is —

(CR^qR^q)_oHet wherein Het is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S substituted with 0, 1, 2, or 3 substituents independently selected from R¹⁰;

or R⁹ is a saturated or unsaturated 4- or 5-membered ring heterocycle containing a single nitrogen atom, wherein the ring is substituted with 0, 1 or 2 substituents independently selected from halo, C_1-2haloalkyl and C_1-3alkyl.

192. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound according to claim 35.

198. A pharmaceutical composition comprising a compound according to any one of claim 35 and a pharmaceutically-acceptable diluent or carrier.

56. A compound having the structure:

57. The compound according to claim 56, wherein R¹ is

58. The compound according to claim 56, wherein R⁷ is C_2-6alkyl or C_1-4haloalkyl.

59. The compound according to claim 56, wherein R¹ is a naphthyl substituted by 0, 1, 2 or 3 substituents independently selected from R⁵.

60. The compound according to claim 56, wherein R¹ is Rⁱ substituted by 1, 2 or 3 substituents independently selected from R⁵.

61. The compound according to claim 60, wherein Rⁱ is substituted by one substituent selected from halo, C_1-4haloalkyl and C_1-5alkyl, and additionally by 0, 1 or 2 substituents independently selected from R⁵.

62. The compound according to claim 56, wherein R¹⁵ is H.

63. The compound according to claim 56, wherein R¹⁵ is R¹⁰, C_1-8alkyl substituted by 0, 1 or 2 substituents selected from R¹⁰, or a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, the heterocycle and bridge being substituted by 0, 1, 2 or 3 substituents independently selected from R¹⁰;

or R¹⁵ is —

(CH₂)_nphenyl substituted by 0, 1, 2 or 3 substituents independently selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, and C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h and —

NR^hC_2-6alkylOR^h.

64. The compound according to claim 56, wherein R¹⁶ is H.

65. The compound according to claim 56, wherein R¹⁶ is halo, —

NHC_1-3alkyl, —

N(C_1-3alkyl)C_1-3alkyl, —

OC_1-3alkyl, —

C_1-2haloalkyl, —

OC_1-2haloalkyl or C_1-3alkyl.

66. The compound according to claim 56, wherein R⁴ is

67. The compound according to claim 66, wherein at least one of R¹⁰, R¹¹, R¹², R¹³ and R¹⁴ is —

OR^h or —

NR^hR^h.

68. The compound according to claim 56, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 2, wherein each of the carbon atoms of the heterocycle is substituted by H, C_1-9alkyl, C_1-4haloalkyl, halo, cyano, oxo, —

OR^h, —

S(═

O)_nC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

OC_1-6alkylC(═

O)OR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^hC_1-6alkyl or —

NR^hC(═

O)C_1-6alkyl; and

saturated carbon atoms may be additionally substituted by ═

O; and

any available nitrogen atoms in the heterocycle are substituted by H, —

C_1-6alkylOR^h, —

C_1-6alkyl, —

C_1-6alkylNR^hR^h, —

C_1-3alkylC(═

O)OR^h, —

C_1-3alkylC(═

O)NR^hR^h, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^hC(═

O)C_1-6alkyl, —

C(═

O)R^j or —

C_1-3alkylR^j.

69. The compound according to claim 56, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1 or 2 atoms selected from O, N and S, wherein each of the carbon atoms of the heterocycle is substituted by H, C_1-9alkyl, C_1-4haloalkyl, halo, cyano, oxo, —

OR^h, —

S(═

O)_nC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

OC_1-6alkylC(═

O)OR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^hC_1-6alkyl or —

NR^hC(═

O)C_1-6alkyl; and

saturated carbon atoms may be additionally substituted by ═

O; and

any available nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^h, —

C_1-6alkyl, —

C_1-6alkylNR^hR^h, —

C_1-3alkylC(═

O)OR^h, —

C_1-3alkylC(═

O)NR^hR^h, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^hC(═

O)C_1-6alkyl, —

C(═

O)R^j or —

C_1-3alkylR^j.

70. The compound according to claim 56, wherein R⁴ is an 8-, 9-, 10- or 11-membered bicyclic ring, containing 1, 2, 3 or 4 N atoms and 0, 1 or 2 atoms selected from S and O with the remainder being carbon atoms, wherein each of the carbon atoms of the ring is substituted by H, C_1-9alkyl, C_1-4haloalkyl, halo, cyano, oxo, —

OR^h, —

S(═

O)_nC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

OC_1-6alkylC(═

O)OR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^hC_1-6alkyl or —

NR^hC(═

O)C_1-6alkyl; and

saturated carbon atoms may be additionally substituted by ═

O; and

any available nitrogen atoms in the ring are substituted by H, —

C_1-6alkylOR^h, —

C_1-6alkyl, —

C_1-6alkylNR^hR^h, —

C_1-3alkylC(═

O)OR^h, —

C_1-3alkylC(═

O)NR^hR^h, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^hC(═

O)C_1-6alkyl, —

C(═

O)R^j or —

C_1-3alkylR^j.

71. The compound according to claim 56, wherein R⁴ is an 8-, 9-, 10- or 11-membered bicyclic ring, containing 0, 1, 2, 3 or 4 N atoms and 0, 1 or 2 atoms selected from S and O with the remainder being carbon atoms, wherein at least one of the carbon atoms of the ring is substituted by C_1-9alkyl, C_1-4haloalkyl, halo, cyano, oxo, —

OR^h, —

S(═

O)_nC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

OC_1-6alkylC(═

O)OR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^hC_1-6alkyl or —

NR^hC(═

O)C_1-6alkyl.

72. The compound according to claim 56, wherein R⁵ and R⁹ are each independently selected from H, C_1-4haloalkyl, halo, nitro, —

OC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, —

CO₂(C_1-6alkyl), —

C(═

O)(C_1-6alkyl), —

C(═

O)NR^hR^h, —

NR^hC(═

O)R^h, —

NR^hC(═

O)NR^hR^h, —

NR^hCO₂(C_1-6alkyl), —

C_1-8alkylOR^h, —

C_1-6alkylNR^hR^h, —

S(═

O)_n(C_1-6alkyl), —

S(═

O)₂NR^hR^h, —

NR^hS(═

O)₂(C_1-6alkyl) and —

OC(═

O)NR^hR^h.

73. The compound according to claim 56, wherein R⁶ and R⁸ are each independently selected from H, C_1-5alkyl, C_1-4haloalkyl, halo, —

OC_1-6alkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h or —

NR^hC_2-6alkylOR^h, —

C_1-8alkylOR^h, —

C_1-6alkylNR^hR^h and —

S(C_1-6alkyl).

74. The compound according to claim 56, wherein R⁷ is independently, at each instance, C_1-8alkyl, C_1-4haloalkyl, —

OC_1-4haloalkyl, —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

NR^hR^h, —

NR^hC_1-4haloalkyl, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h, —

C_1-8alkylOR^h, —

C_1-6alkylNR^hR^h or —

S(C_1-6alkyl).

75. The compound according to claim 56, wherein R¹⁰ and R¹⁴ are each independently selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h and —

NR^hC_2-6alkylOR^h and C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h and —

NP^hC_2-6alkylOR^h.

76. The compound according to claim 56, wherein R¹¹ and R¹³ are independently, at each instance, selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h, —

NR^hC_2-6alkylOR^h and C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h and —

NR^hC_2-6alkylOR^h.

77. The compound according to claim 56, wherein R¹² is independently, at each instance, selected from H, C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h and —

NR^hC_2-6alkylOR^h;

or R¹² is C_1-4alkyl substituted by 0, 1, 2 or 3 groups selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)(C_1-8alkyl), —

C(═

O)O(C_1-8alkyl), —

C(═

O)NR^hR^h, —

C(═

NR^h)NR^hR^h, —

OR^h, —

OC(═

O)(C_1-8alkyl), —

OC(═

O)NR^hR^h, —

OC(═

O)N(R^h)S(═

O)₂(C_1-8alkyl), —

OC_2-6alkylNR^hR^h, —

OC_2-6alkylOR^h, —

SR^h, —

S(═

O)(C_1-8alkyl), —

S(═

O)₂(C_1-8alkyl), —

S(═

O)₂NR^hR^h, —

S(═

O)₂N(R^h)C(═

O)(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)O(C_1-8alkyl), —

S(═

O)₂N(R^h)C(═

O)NR^hR^h, —

NR^hR^h, —

N(R^h)C(═

O)(C_1-8alkyl), —

N(R^h)C(═

O)O(C_1-8alkyl), —

N(R^h)C(═

O)NR^hR^h, —

N(R^h)C(═

NR^h)NR^hR^h, —

N(R^h)S(═

O)₂(C_1-8alkyl), —

N(R^h)S(═

O)₂NR^hR^h, —

NR^hC_2-6alkylNR^hR^h and —

NR^hC_2-6alkylOR^h.

78. The compound according to claim 56, wherein Y is O.

79. The compound according to claim 56, wherein Y is S.

166. A compound according to claim 56, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:

7-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yloxy]-quinoline,

2-(3-methoxy-phenoxy)-4-(4-trifluoromethyl-phenyl)-pyridine,

8-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yloxy]-quinolin-2-ylamine,

4-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yloxy]-benzothiazol-2-ylamine,

N-{4-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yloxy]-benzothiazol-2-yl}-acetamide,

8-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yloxy]-quinoline, and

2-methyl-5-[4-(4-trifluoromethyl-phenyl)-pyridin-2-yloxy]-benzothiazole.

193. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound according to claim 56.

199. A pharmaceutical composition comprising a compound according to any one of claim 56 and a pharmaceutically-acceptable diluent or carrier.

80. A compound having the structure:

81. A compound according to claim 80, wherein:

R¹ is

R² is H, —

OR^m, halo, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic or 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p;

R^p is independently at each instance C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m or —

NR^mC_2-6alkylOR^m; and

Y is O or NH.

82. A compound according to claim 81, wherein:

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)OR^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

83. A compound according to claim 81, wherein R⁴ is a phenyl ring that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

84. A compound according to claim 81, wherein R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

NR^mR^m or —

NR^m—

C_1-4haloalkyl.

85. A compound according to claim 81, wherein R⁷ is C_1-5alkyl, C_1-4haloalkyl, I, Br or Cl.

86. A compound according to claim 81, wherein R⁷ is tert-butyl or trifluoromethyl.

87. A compound according to claim 81, wherein R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic ring containing 0, 1, 2 or 3 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 1, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

88. A compound according to claim 81, wherein R^o is a saturated, partially-saturated or unsaturated 6-membered ring containing 0, 1, 2 or 3 N atoms, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

89. A compound according to claim 81, wherein Y is O.

90. A compound according to claim 81, wherein Y is NH.

91. A compound according to claim 80, wherein:

R¹ is

R² is H, —

OR^m, halo, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

[C_1-8alkyl, C_1-5haloalkyl, I, Br or Cl]

R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic or 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p;

R^p is independently at each instance C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m or —

NR^mC_2-6alkylOR^m; and

Y is O or NH.

92. A compound according to claim 91, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

93. A compound according to claim 91, wherein R⁴ is a phenyl ring that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

94. A compound according to claim 91, wherein R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

NR^mR^m or —

NR^m—

C_1-4haloalkyl.

95. A compound according to claim 91, wherein R⁷ is C_1-5alkyl, C_1-4haloalkyl, I, Br or Cl.

96. A compound according to claim 91, wherein R⁷ is tert-butyl or trifluoromethyl.

97. A compound according to claim 91, wherein R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic ring containing 0, 1, 2 or 3 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 1, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

98. A compound according to claim 91, wherein R^o is a saturated, partially-saturated or unsaturated 6-membered ring containing 0, 1, 2 or 3 N atoms, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

99. A compound according to claim 91, wherein Y is O.

100. A compound according to claim 91, wherein Y is NH.

101. A compound according to claim 80, wherein:

R¹ is

R² is H, —

OR^m, halo, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated, partially-saturated or unsaturated 8-, 9-, 10 or 11-membered bicyclic heterocycle containing 1, 2, 3, 4 or 5 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 2, but excluding quinolin-6-yl, 4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl, benzothiazol-2-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, wherein the heterocycle is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9alkyl, oxo, C_1-4haloalkyl, halo, nitro, cyano, —

OR^m, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m, —

NR^m—

C_1-6alkylOR^m, —

C(═

O)C_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^mC_1-6alkyl, —

NR^mC(═

O)C_1-6alkyl —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m;

wherein R⁴ is not 2-aminocarbonylmethyl-2,3-dihydro-benzo[1,4]dioxin-8-yl, 2-cyanomethyl-2,3-dihydro-benzo[1,4]dioxin-8-yl, quinolin-3-yl, 3H-quinazolin-4-on-3-yl, benzo[1,3]dioxol-5-yl, 3,3-dimethyl-1,3-dihydro-indol-2-on-6-yl or 4,4-dimethyl-3,4-dihydro-1H-quinolin-2-on-7-yl;

R⁷ is C_1-8alkyl, C_1-5haloalkyl, I or Br

R⁹ is H, C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

Y is NH; and

Z is CR⁸ or N.

102. A compound according to claim 101, wherein R⁴ is a heterocycle selected from indole, 3H-indole, benzo[b]furan, benzothiophene, 1H-indazole, benzimidazole, benzthiazole, 1H-benzotriazole, 7-quinoline, 8-quinoline, 1,2,3,4-tetrahydroquinoline, isoquinoline, cinnoline, phthalazine, quinazoline and quinoxaline, wherein the heterocycle is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9-alkyl, oxo, C_1-4haloalkyl, halo, nitro, cyano, —

OR^m, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m, —

NR^m—

C_1-6alkylOR^m, —

C(═

O)C_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^mC_1-6alkyl, —

NR^mC(═

O)C_1-6alkyl —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m.

103. A compound according to claim 101, wherein R⁴ is a heterocycle selected from 6-indole, 7-indole, 6-3H-indole, 7-3H-indole, 6-benzo[b]furan, 7-benzo[b]furan, 6-benzothiophene, 7-benzothiophene, 6-1H-indazole, 7-1H-indazole, benzimidazole, benzthiazole, 1H-benzotriazole, 7-quinoline, 8-quinoline, 7-1,2,3,4-tetrahydroquinoline, 8-1,2,3,4-tetrahydroquinoline, isoquinolin-7-yl, isoquinolin-8-yl, 7-cinnoline, 8-cinnoline, phthalazine, 7-quinazoline, 8-quinazoline and quinoxaline, wherein the heterocycle is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9alkyl, oxo, C_1-4haloalkyl, halo, nitro, cyano, —

OR^m, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m-C_1-6alkylNR^mR^m, —

NR^m—

C_1-6alkylOR^m, —

C(═

O)C_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^mC_1-6alkyl, —

NR^mC(═

O)C_1-6alkyl —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m.

104. A compound according to claim 101, wherein R⁹ is C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m.

105. A compound according to claim 101, wherein R⁹ is H.

106. A compound according to claim 101, wherein Z is CR⁸.

107. A compound according to claim 101, wherein Z is N.

108. A compound according to claim 101, wherein R⁷ is tert-butyl or trifluoromethyl.

109. A compound according to claim 80, wherein:

R¹ is

R² is C_1-6alkyl substituted by 1, 2 or 3 substituents selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

R)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m;

or

R² is

R² is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m, and the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

R⁷ is C_2-8alkyl, C_1-5haloalkyl, I, Br;

R⁹ is independently, at each instance, H, C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

Y is NH; and

Z is CR⁸ or N.

110. A compound according to claim 109, wherein R² is C_1-6alkyl substituted by 1, 2 or 3 substituents selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

R)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m;

111. A compound according to claim 109, wherein R² is —

(C(R^q)₂)_ophenyl, wherein the phenyl is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m.

112. A compound according to claim 109, wherein R² is —

(C(R^q)₂)_oR^r, wherein R^r is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m;

113. A compound according to claim 109, wherein R⁴ is a phenyl ring that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m; and

the bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

114. A compound according to claim 109, wherein R⁷ is tert-butyl or trifluoromethyl.

115. A compound according to claim 109, wherein R⁹ is H.

116. A compound according to claim 109, wherein Z is CR⁸.

117. A compound according to claim 109, wherein Z is N.

118. A compound according to claim 80, wherein:

R¹ is

R² is H, —

OR^m, Cl, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 2, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

ORⁿ, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m;

wherein R⁴ is not unsubstituted phenyl;

R⁹ is independently, at each instance, H, C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

Y is NH; and

Z is CR⁸ or N.

119. A compound according to claim 118, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 1, 2 or 3 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 1, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

ORⁿ, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylor^m;

120. A compound according to claim 118, wherein Z is CR⁸.

121. A compound according to claim 118, wherein Z is N.

150. A compound according to claim 101, wherein R⁷ is tert-butyl or trifluoromethyl.

155. A compound according to claim 109, wherein R⁴ is a phenyl ring that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m; and

the bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

194. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound according to claim 80.

200. A pharmaceutical composition comprising a compound according to any one of claim 80 and a pharmaceutically-acceptable diluent or carrier.

122. A compound having the structure:

123. A compound according to claim 122, wherein:

R¹ is

R² is H, —

OR^m, halo, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic or 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p;

R^p is independently at each instance C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m or —

NR^mC_2-6alkylOR^m; and

Y is O or NH.

124. A compound according to claim 123, wherein:

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)OR^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

125. A compound according to claim 123, wherein R⁴ is a phenyl ring that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

126. A compound according to claim 123, wherein R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

NR^mR^m or —

NR^m—

C_1-4haloalkyl.

127. A compound according to claim 123, wherein R⁷ is C_1-5alkyl, C_1-4haloalkyl, I, Br or Cl.

128. A compound according to claim 123, wherein R⁷ is tert-butyl or trifluoromethyl.

129. A compound according to claim 123, wherein R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic ring containing 0, 1, 2 or 3 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 1, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

130. A compound according to claim 123, wherein R^o is a saturated, partially-saturated or unsaturated 6-membered ring containing 0, 1, 2 or 3 N atoms, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

131. A compound according to claim 123, wherein Y is O.

132. A compound according to claim 123, wherein Y is NH.

133. A compound according to claim 122, wherein:

R¹ is

R² is H, —

OR^m, halo, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mRm or —

NR^m—

C_1-6alkylOR^m;

[C_1-8alkyl, C_1-5haloalkyl, I, Br or Cl]

R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic or 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p;

R^p is independently at each instance C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m or —

NR^mC_2-6alkylOR^m; and

Y is O or NH.

134. A compound according to claim 133, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

135. A compound according to claim 133, wherein R⁴ is a phenyl ring that is vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups.

136. A compound according to claim 133, wherein R⁷ is C_1-9alkyl, C_1-4haloalkyl, halo, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

NR^mR^m or —

NR^m—

C_1-4haloalkyl.

137. A compound according to claim 133, wherein R⁷ is C_1-5alkyl, C_1-4haloalkyl, I, Br or Cl.

138. A compound according to claim 133, wherein R⁷ is tert-butyl or trifluoromethyl.

139. A compound according to claim 133, wherein R^o is a saturated, partially-saturated or unsaturated 5-, 6- or 7-membered monocyclic ring containing 0, 1, 2 or 3 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 1, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

140. A compound according to claim 133, wherein R^o is a saturated, partially-saturated or unsaturated 6-membered ring containing 0, 1, 2 or 3 N atoms, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from R^p.

141. A compound according to claim 133, wherein Y is O.

142. A compound according to claim 133, wherein Y is NH.

143. A compound according to claim 122, wherein:

R¹ is

R² is H, —

OR^m, halo, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated, partially-saturated or unsaturated 8-, 9-, 10 or 11-membered bicyclic heterocycle containing 1, 2, 3, 4 or 5 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 2, but excluding quinolin-6-yl, 4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl, benzothiazol-2-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, wherein the heterocycle is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9alkyl, oxo, C_1-4haloalkyl, halo, nitro, cyano, —

OR^m, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m, —

NR^m—

C_1-6alkylOR^m, —

C(═

O)C_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^mC_1-6alkyl, —

NR^mC(═

O)C_1-6alkyl —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m;

wherein R⁴ is not 2-aminocarbonylmethyl-2,3-dihydro-benzo[1,4]dioxin-8-yl, 2-cyanomethyl-2,3-dihydro-benzo[1,4]dioxin-8-yl, quinolin-3-yl, 3H-quinazolin-4-on-3-yl, benzo[1,3]dioxol-5-yl, 3,3-dimethyl-1,3-dihydro-indol-2-on-6-yl or 4,4-dimethyl-3,4-dihydro-1H-quinolin-2-on-7-yl;

R⁷ is C_1-8alkyl, C_1-5haloalkyl, I or Br

R⁹ is H, C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

Y is NH; and

Z is CR⁸ or N.

144. A compound according to claim 143, wherein R⁴ is a heterocycle selected from indole, 3H-indole, benzo[b]furan, benzothiophene, 1H-indazole, benzimidazole, benzthiazole, 1H-benzotriazole, 7-quinoline, 8-quinoline, 1,2,3,4-tetrahydroquinoline, isoquinoline, cinnoline, phthalazine, quinazoline and quinoxaline, wherein the heterocycle is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9-alkyl, oxo, C_1-4haloalkyl, halo, nitro, cyano, —

OR^m, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m-C_1-6alkylNR^mR^m, —

NR^m—

C_1-6alkylOR^m, —

C(═

O)C_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^mC_1-6alkyl, —

NR^mC(═

O)C_1-6alkyl —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m.

145. A compound according to claim 143, wherein R⁴ is a heterocycle selected from 6-indole, 7-indole, 6-3H-indole, 7-3H-indole, 6-benzo[b]furan, 7-benzo[b]furan, 6-benzothiophene, 7-benzothiophene, 6-1H-indazole, 7-1H-indazole, benzimidazole, benzthiazole, 1H-benzotriazole, 7-quinoline, 8-quinoline, 7-1,2,3,4-tetrahydroquinoline, 8-1,2,3,4-tetrahydroquinoline, isoquinolin-7-yl, isoquinolin-8-yl, 7-cinnoline, 8-cinnoline, phthalazine, 7-quinazoline, 8-quinazoline and quinoxaline, wherein the heterocycle is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-9alkyl, oxo, C_1-4haloalkyl, halo, nitro, cyano, —

OR^m, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m-C_1-6alkylNR^mR^m, —

NR^m—

C_1-6alkylOR^m, —

C(═

O)C_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^mC_1-6alkyl, —

NR^mC(═

O)C_1-6alkyl —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m.

146. A compound according to claim 143, wherein R⁹ is C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m.

147. A compound according to claim 143, wherein R⁹ is H.

148. A compound according to claim 143, wherein Z is CR⁸.

149. A compound according to claim 143, wherein Z is N.

151. A compound according to claim 122, wherein:

R¹ is

R² is C_1-6alkyl substituted by 1, 2 or 3 substituents selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

R)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m or —

NR^mC_2-6alkylOR^m;

or

R² is

R² is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S that is optionally vicinally fused with a saturated or unsaturated 3- or 4-atom bridge containing 0, 1, 2 or 3 atoms selected from O, N and S with the remaining atoms being carbon, so long as the combination of O and S atoms is not greater than 2, wherein the ring and bridge are substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m; and

the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═

O groups;

R⁷ is C_2-8alkyl, C_1-5haloalkyl, I, Br;

R⁹ is independently, at each instance, H, C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

Y is NH; and

Z is CR⁸ or N.

152. A compound according to claim 151, wherein R² is C_1-6alkyl substituted by 1, 2 or 3 substituents selected from C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

R)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m;

153. A compound according to claim 151, wherein R² is —

(C(R^q)₂)_ophenyl, wherein the phenyl is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m.

154. A compound according to claim 151, wherein R² is —

(C(R^q)₂)_oR^r, wherein R^r is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)ORⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and —

NR^mC_2-6alkylOR^m;

156. A compound according to claim 151, wherein R⁷ is tert-butyl or trifluoromethyl.

157. A compound according to claim 151, wherein R⁹ is H.

158. A compound according to claim 151, wherein Z is CR⁸.

159. A compound according to claim 151, wherein Z is N.

160. A compound according to claim 122, wherein:

R¹ is

R² is H, —

OR^m, Cl, C_1-3haloalkyl or C_1-6alkyl;

R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 0, 1, 2 or 3 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 2, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

NR^m)NR^mR^s, —

N(R^m)S(═

O)₂R^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)R^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m;

wherein R⁴ is not unsubstituted phenyl;

R⁹ is independently, at each instance, H, C_1-9alkyl, C_1-4haloalkyl, halo, nitro, cyano, —

OC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^mR^m, —

O—

C_1-6alkylOR^m, —

NR^mR^m, —

NR^m—

C_1-4haloalkyl, —

NR^m—

C_1-6alkylNR^mR^m or —

NR^m—

C_1-6alkylOR^m;

Y is NH; and

Z is CR⁸ or N.

161. A compound according to claim 160, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring containing 1, 2 or 3 atoms selected from O, N and S, so long as the combination of O and S atoms is not greater than 1, wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

ORⁿ, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂NR^mR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m, —

NR^mC_2-6alkylOR^m, —

C(═

O)R^s, —

C(═

O)OR^s, —

C(═

O)NR^mR^s, —

C(═

NR^m)NR^mR^s, —

OR^s, —

OC(═

O)R^s, —

OC(═

O)NR^mR^s, —

OC(═

O)N(R^m)S(═

O)₂R^s, —

OC_2-6alkylNR^mR^s, —

OC_2-6alkylOR^s, —

SR^s, —

S(═

O)R^s, —

S(═

O)₂R^s, —

S(═

O)₂NR^mR^s, —

S(═

O)₂N(R^m)C(═

O)R^s, —

S(═

O)₂N(R^m)C(═

O)OR^s, —

S(═

O)₂N(R^m)C(═

O)NR^mR^s, —

NR^mR^s, —

N(R^m)C(═

O)R^s, —

N(R^m)C(═

O)OR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)C(═

O)NR^mR^s, —

N(R^m)S(═

O)₂NR^mR^s, —

NR^mC_2-6alkylNR^mR^s, —

NR^mC_2-6alkylOR^s and C_1-4alkyl substituted by 1 or 2 groups selected from C_1-2haloalkyl, halo, cyano, nitro, —

C(═

O)Rⁿ, —

C(═

O)NR^mR^m, —

C(═

NR^m)NR^mR^m, —

OR^m, —

OC(═

O)Rⁿ, —

OC(═

O)NR^mR^m, —

OC(═

O)N(R^m)S(═

O)₂Rⁿ, —

OC_2-6alkylNR^mR^m, —

OC_2-6alkylOR^m, —

SR^m, —

S(═

O)Rⁿ, —

S(═

O)₂Rⁿ, —

S(═

O)₂RⁿR^m, —

S(═

O)₂N(R^m)C(═

O)Rⁿ, —

S(═

O)₂N(R^m)C(═

O)ORⁿ, —

S(═

O)₂N(R^m)C(═

O)NR^mR^m, —

NR^mR^m, —

N(R^m)C(═

O)Rⁿ, —

N(R^m)C(═

O)ORⁿ, —

N(R^m)C(═

O)NR^mR^m, —

N(R^m)C(═

NR^m)NR^mR^m, —

N(R^m)S(═

O)₂Rⁿ, —

N(R^m)S(═

O)₂NR^mR^m, —

NR^mC_2-6alkylNR^mR^m and —

NR^mC_2-6alkylOR^m;

162. A compound according to claim 160, wherein Z is CR⁸.

163. A compound according to claim 160, wherein Z is N.

195. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound according to claim 122.

201. A pharmaceutical composition comprising a compound according to any one of claim 122 and a pharmaceutically-acceptable diluent or carrier.

169. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound having the structure:

170. The method according to claim 169, wherein:

R¹ is

 

or a naphthyl or saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the naphthyl, heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷;

R² is H, hydroxy, halo, C_1-6alkyl substituted by 0, 1 or 2 substituents selected from R¹⁰,

 

or a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷; and

R³ is H or C_1-4alkyl.

171. The method according to claim 169, wherein R¹ is

172. The method according to claim 171, wherein R⁷ is independently, at each instance, C_2-9alkyl or C_1-4haloalkyl.

173. The method according to claim 169, wherein R¹ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷.

174. The method according to claim 173, wherein R² is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷.

175. The method according to claim 169, wherein R² is

176. The method according to claim 175, wherein R² is

177. The method according to claim 175, wherein R² is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents independently selected from R⁵, R⁶ and R⁷.

178. The method according to claim 169, wherein R¹ and R² together are

179. The method according to claim 169, wherein R¹ and R³ together are

180. The method according to claim 169, wherein X and R² together are ═

N—

CH═

CH—

, ═

C—

O—

, ═

C—

S—

, or ═

C—

NR^a—

.

181. The method according to claim 169, wherein:

R⁴ is

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^a—

or —

O—

.

182. The method according to claim 169, wherein:

R⁴ is

L³ is a 2- or 3-atom, saturated or unsaturated, bridge containing 1, 2 or 3 carbon atoms and 0 or 1 atoms independently selected from O, N and S, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, —

OR^a, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

NR^aR^a, —

C_1-6alkylNR^aR^a, —

C(═

O)OR^a, —

C(═

O)NR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

OC(═

O)C_1-6alkyl, —

NR^aC(═

O)C_1-6alkyl, —

C_1-3alkylOC(═

O)C_1-6alkyl or —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

C_1-6alkylNR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, —

C(═

O)R^c or —

C_1-3alkylR^c;

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^b—

or —

O—

.

183. A compound according to claim 169, wherein:

R⁴ is

L³ is a 2- or 3-atom, saturated or unsaturated, bridge containing 1, 2 or 3 carbon atoms and 0, 1 or 2 atoms independently selected from O, N and S, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, —

OR^a, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

NR^aR^a, —

C_1-6alkylNR_aR_a, —

C(═

O)OR^a, —

C(═

O)NR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

OC(═

O)C_1-6alkyl, —

NR^aC(═

O)C_1-6alkyl, —

C_1-3alkylOC(═

O)C_1-6alkyl or —

C_1-3alkylNR^aC(═

O)C_1-6alkyl and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

C_1-6alkylNR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, —

C(═

O)R^c or —

C_1-3alkylR^c;

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^b—

or —

O—

.

184. A compound according to claim 169, wherein:

R⁴ is

L³ is a 2- or 3-atom, saturated or unsaturated, bridge containing 1, 2 or 3 carbon atoms and 0, 1 or 2 atoms independently selected from O, N and S, wherein the each of the carbon atoms in the bridge is substituted by H, ═

O, —

OR^a, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

NR^aR^a, —

C_1-6alkylNR^aR^a, —

C(═

O)OR^a, —

C(═

O)NR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

OC(═

O)C_1-6alkyl, —

NR^aC(═

O)C_1-6alkyl, —

C_1-3alkylOC(═

O)C_1-6alkyl or —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —

C_1-6alkylOR^a, —

C_1-6alkyl, —

C_1-6alkylNR^aR^a, —

C_1-3alkylC(═

O)OR^a, —

C_1-3alkylC(═

O)NR^aR^a, —

C_1-3alkylOC(═

O)C_1-6alkyl, —

C_1-3alkylNR^aC(═

O)C_1-6alkyl, —

C(═

O)R^c or —

C_1-3alkylR^c;

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^b—

or —

O—

.

185. A compound according to claim 169, wherein:

R⁴ is

R^b is H, C_1-6alkyl, —

C(═

O)C_1-6alkyl, C_1-6alkyl-O—

R^a; and

Y² is —

NR^a—

or —

O—

.

186. The method according to claim 169, wherein R⁴ is 10-membered bicyclic ring comprising fused 6-membered rings, containing 0, 1, 2, 3 or 4 N atoms with the remainder being carbon atoms, with at least one of the 6-membered rings being aromatic, wherein the carbon atoms are substituted by H, halo, OR^a, NR^aR^a, C_1-6alkyl and C_1-3haloalkyl;

and saturated carbon atoms may be additionally substituted by ═

O.

187. The method according to claim 169, wherein:

R⁴ is

R¹⁰ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

R¹¹ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylR^c, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

C_1-6alkylNR^aR^a;

R¹² is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

R¹³ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl; and

R¹⁴ is independently, at each instance, H, C_1-9alkyl, —

C_1-3alkylOR^a, C_1-4haloalkyl, halo, nitro, cyano, —

OR^a, —

S(═

O)_nC_1-6alkyl, —

O—

C_1-4haloalkyl, —

O—

C_1-6alkylNR^aR^a, —

O—

C_1-6alkylOR^a, —

O—

C_1-6alkylC(═

O)OR^a, —

NR^aR^a, —

NR^a—

C_1-4haloalkyl, —

NR^a—

C_1-6alkylNR^aR^a, —

NR^a—

C_1-6alkylOR^a, —

C(═

O)C_1-6alkyl, —

C(═

O)OC_1-6alkyl, —

OC(═

O)C_1-6alkyl, —

C(═

O)NR^aC_1-6alkyl or —

NR^aC(═

O)C_1-6alkyl;

wherein one of R¹⁰ and R¹² is not H.

188. The method according to claim 169, wherein R⁴ is a saturated or unsaturated 5- or 6-membered ring heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein no more than 2 of the ring members are O or S, wherein the heterocycle is optionally fused with a phenyl ring, and the heterocycle or fused phenyl ring is substituted by 0, 1, 2 or 3 substituents selected from halo, C_1-4haloalkyl, —

OR^a and —

NR^aR^a.

189. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound having the structure:

190. A method of treating acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders, comprising the step of administering a compound having the structure: