Novel Compounds

• US 20070259888A1
• Filed: 04/30/2007
• Published: 11/08/2007
• Est. Priority Date: 05/02/2006
• Status: Abandoned Application

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Tomaszewski, Miroslaw, Cheng, Yun-Xing, Luo, Xuehong
• Application Number:
  US11/741,888
• Publication Number:
  US 20070259888A1
• Time in Patent Office: Days
• US Class Current: 514/255.50
• 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 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 : Tobacco-abuse
• CPC Class Codes: A61P 25/36 : Opioid-abuse
• 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• 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: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07C 235/50 : having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07C 235/54 : having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07D 207/327 : Radicals substituted by 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 209/08 : 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 209/42 : 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 211/14 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 211/18 : with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 211/22 : by oxygen atoms
• CPC Class Codes: C07D 211/38 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 211/44 : attached in position 4
• CPC Class Codes: C07D 213/56 : Amides
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 233/90 : 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 235/26 : Oxygen atoms
• CPC Class Codes: C07D 241/26 : with nitrogen atoms directly attached to ring carbon atoms
• CPC Class Codes: C07D 249/18 : Benzotriazoles
• CPC Class Codes: C07D 261/18 : Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
• CPC Class Codes: C07D 263/32 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 263/34 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 265/36 : condensed with one six-membered ring
• CPC Class Codes: C07D 277/62 : Benzothiazoles
• CPC Class Codes: C07D 295/135 : with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 307/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/80 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 307/85 : attached in position 2
• CPC Class Codes: C07D 309/06 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 317/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 319/16 : condensed with one six-membered ring
• CPC Class Codes: C07D 321/10 : condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 333/24 : Radicals substituted by 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 333/38 : 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 333/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• 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 405/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/12 : 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 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems

Abstract

Compounds of Formulae I, or pharmaceutically acceptable salts thereof:
wherein X, R¹, R² and R³ are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

Claims

1. A compound of formula I, a pharmaceutically acceptable salt thereof, diastereomer, enantiomer, or mixture thereof:

wherein

R¹ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl, wherein said C_6-10aryl, C_2-9heteroaryl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl are optionally substituted with one or more group selected from C_6-10aryl, C_1-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

O(CH₂)_m—

OR, R, —

C(═

O)—

R, —

CO₂R, —

SO₂R, —

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, —

(CH₂)_mNHC(═

O)—

NR₂, —

NHC(═

O)—

R, —

N[C(═

O)R]₂, —

(CH₂)_mNHS(═

O)₂—

R, —

(CH₂)_mNHC(═

O)—

R, —

(CH₂)_mN[C(═

O)—

R]₂ and —

C(═

O)—

NR₂;

R² and R³ are independently selected from C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy wherein said C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy are optionally substituted by one or more groups selected from amino, halogen, C_1-6alkoxy and —

CN;

or R² and R³ together with the nitrogen connected thereto form a heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

(CH₂)_mOR, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂;

each R is independently hydrogen, C_1-6alkyl, C_2-6alkenyl or halogenated C_1-6alkyl; and

X is selected from —

C(═

O)—

, —

C(═

O)—

NH—

, —

C(═

O)—

O— and

—

S(═

O)₂—

,

with a proviso that

when X is —

C(═

O)— and

R² and R³ together with the nitrogen connected thereto form said piperidinyl;

R¹ is not 4-amino-5-chloro-2-alkoxylphenyl, 4-amino-5-chloro-2-cycloalkoxyphenyl, 4-amino-5-chloro-2-cycloalkyl-alkoxy-phenyl, 4-butoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-isobutoxyphenyl, 4-benzoyloxyphenyl and 7-(2,3-dihydro)benzofuranyl.

2. A compound as claimed in claim 1, wherein

said R² and R³ together with the nitrogen connected thereto form a heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl —

CN, —

SR, —

OR, —

(CH₂)_mOR, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂.

3. A compound as claimed in claim 1, wherein

said R² and R³ together with the nitrogen connected thereto form a group selected from piperidinyl, 1,4-dixo-8-azaspiro[4,5]dec-8-yl, piperazinyl, methyl(2-phenylethyl)amino, methyl(pyridin-3-ylmethyl)amino, (4-ethylbenzyl)(methyl)amino, methyl(1-methylpyrrolidin-3-yl)amino, methyl(3-methylbutyl)amino, methyl(propyl)amino, methyl(butyl)amino, butyl(ethyl)amino, diethylamino, benzyl(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, and azepan-1-yl, wherein said piperidinyl, 1,4-dixo-8-azaspiro[4,5]dec-8-yl, piperazinyl, methyl(2-phenylethyl)amino, methyl(pyridin-3-ylmethyl)amino, (4-ethylbenzyl)(methyl)amino, methyl(1-methylpyrrolidin-3-yl)amino, methyl(3-methylbutyl)amino, methyl(propyl)amino, methyl(butyl)amino, butyl(ethyl)amino, diethylamino, benzyl(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, and azepan-1-yl are optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl —

CN, —

SR, —

OR, —

(CH₂)_mOR, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂.

4. A compound as claimed in claim 1, wherein

said R¹ is selected from 2-cyclopentylethyl, cyclopropylmethyl, methyl, cyclohexyl, cyclopentylmethyl, chromanyl, ethyl, pentyl, 2-phenylethyl, phenyl, benzyl, pyridinyl, pyridinylethyl, 1-benzofuranyl, benzothienyl, furyl, imidazolyl, pyrazolo[1,5-a]pyrimidinyl, pyrazinyl, 1,3-benzothiazolyl, indolyl, indazolyl, thienyl, 1,3-benzodioxinyl, tetrahydro-2H-pyran-4-ylmethyl, 1-H-1,2,3-benzotriazol-1-yl, 2-(thien-2-yl)ethyl, (1-benzofuran-4-yl)methyl, 1,3-oxazolyl, 1H-pyrazol-1-yl, 2,3-dihydro-1-benzofuran-5-yl, 1,3-benzodioxol-5-yl, 2-oxo-2,3-dihydro-2H-benzimidazolyl, isoxazolyl, imidazo[1,2,a]pyridinyl, 2-3-dioxo-2,3-dihydro-1H-indol-1-yl, 3,4-dihydro-2H-1,4-benzoxazinyl;

pyrazolyl, 1H-tetrazol-1-yl-methyl, and 3,4-dihydro-2H-1,5-benzodioxepinyl, optionally substituted by 1H-pyrazol-1-yl, fluoro, chloro, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, t-butyl, cyano, bromo, 1,3-oxazol-5-yl, 1H-imidazol-1-yl, (4-oxopiperidin-1-yl)carbonyl, pyridin-3-ylmethyl, [(butylamino)carbonyl]amino, 1,1-dioxidothiomorpholin-4-yl, aminosulfonyl, morpholin-4-yl, diethylaminomethyl, acetyl, (3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methyl, 1-oxo-indan-4-yl, dimethylaminomethyl, methyl, pyrrolidin-1-yl, ethylthio, acetylamino, dimethylamino, 1H-pyrrol-1-yl, ethyl, ethoxy, fluorophenoxy, propyl, phenyl, methoxycarbonyl, diacetylamino, (methylsulfonylamino)methyl, (cyclopropylsulfonylamino)methyl, 1H-tetrazol-1-yl, pyrazolyl, methylaminocarbonylamino, dimethylaminocarbonylamino, and (methylthio)pyrimidin-4-yl.

5. A compound as claimed in claim 1, wherein

said R² and R³ together with the nitrogen connected thereto form a group selected from piperidinyl, 1,4-dixo-8-azaspiro[4,5]dec-8-yl, piperazinyl, methyl(2-phenylethyl)amino, methyl(pyridin-3-ylmethyl)amino, (4-ethylbenzyl)(methyl)amino, methyl(1-methylpyrrolidin-3-yl)amino, methyl(3-methylbutyl)amino, methyl(propyl)amino, methyl(butyl)amino, butyl(ethyl)amino, diethylamino, benzyl(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, and azepan-1-yl, wherein said piperidinyl, 1,4-dixo-8-azaspiro[4,5]dec-8-yl, piperazinyl, methyl(2-phenylethyl)amino, methyl(pyridin-3-ylmethyl)amino, (4-ethylbenzyl)(methyl)amino, methyl(1-methylpyrrolidin-3-yl)amino, methyl(3-methylbutyl)amino, methyl(propyl)amino, methyl(butyl)amino, butyl(ethyl)amino, diethylamino, benzyl(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, and azepan-1-yl are optionally substituted with one or more group selected from phenyl, benzyl, methyl, fluoro, trifluoromethyl, methoxy, allyloxy, (2E)-but-2-en-1-yloxy, (allyloxy)methyl, methoxymethyl, ethoxymethyl, propyl, butyl, pentyl, hexyl, cyclopentyl, pyridin-4-ylmethyl, ethoxy, butoxy, 2-methoxyethoxy, cyclohexyl, and thienylmethyl.

6. A compound as claimed in claim 1, wherein said R² and R³ together with the nitrogen connected thereto form a group selected from piperidinyl, wherein said piperidinyl is optionally substituted with one or more group selected from phenyl, benzyl, methyl, fluoro, trifluoromethyl, methoxy, allyloxy, (2E)-but-2-en-1-yloxy, (allyloxy)methyl, methoxymethyl, ethoxymethyl, propyl, butyl, pentyl, hexyl, cyclopentyl, pyridin-4-ylmethyl, ethoxy, butoxy, 2-methoxyethoxy, cyclohexyl, and thienylmethyl.

13. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

16. A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 1.

19. A method for the therapy of Alzheimer'"'"'s disease in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 1.

22. A method for the therapy of schizophrenia in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 1.

28. A method for the therapy of anxiety in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 1.

31. A method for the therapy of depression in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 1.

7. A compound selected from

trans-(+/−

)-4-fluoro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-6-(trifluoromethyl)nicotinamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-4-(1H-pyrazol-1-yl)benzamide;

trans-(+/−

)-5-chloro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1-benzofuran-2-carboxamide;

trans-(+/−

)-2-(4-methoxyphenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-4-(difluoromethoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-(2-methoxyethoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+)-4-(2-methoxyethoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(−

)4-(2-methoxyethoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-3-cyclopentyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-3-(4-chlorophenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-3-(2-methoxyphenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-4-tert-butyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-methoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-cyano-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-bromo-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-chloro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-6-(1H-imidazol-1-yl)-N-[2-(piperidin-1 ylmethyl)cyclohexyl]nicotinamide;

trans-(+/−

)-4-(1,3-oxazol-5-yl)-N-[-2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-6-methoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]nicotinamide;

trans-(+/−

)-4-(1H-imidazol-1-yl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-[(4-oxopiperidin-1-yl)carbonyl]-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-2-pyridin-3-ylacetamide;

trans-(+/−

)-2-{[(butylamino)carbonyl]amino}-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-(1,1-dioxidothiomorpholin-4-yl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-(aminosulfonyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-2-morpholin-4-yl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]isonicotinamide;

trans-(+/−

)-4-[(diethylamino)methyl]-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1-benzothiophene-3-carboxamide;

trans-(+/−

)-4-acetyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-[(3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methyl]-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-1-oxo-N-[2-(piperidin-1-ylmethyl)cyclohexyl]indane-4-carboxamide;

trans-(+/−

)-5-[(dimethylamino)methyl]-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-2-furamide;

trans-(+/−

)-1-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-imidazole-4-carboxamide;

trans-(+/−

)-2-(4-chlorophenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-6-pyrrolidin-1-ylnicotinamide;

trans-(+/−

)-5-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]pyrazine-2-carboxamide;

trans-(+/−

)-4-(ethylthio)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1,3-benzothiazole-6-carboxamide;

trans-(+/−

)-4-(acetylamino)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-5-methoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-indole-2-carboxamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]thiophene-3-carboxamide;

trans-(+/−

)-2-phenyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-4-(trifluoromethoxy)benzamide;

trans-(+/−

)-3-(2-chlorophenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-4-cyano benzamide;

trans-(+/−

)-3-(3-chlorophenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-6-fluoro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-4H-1,3-benzodioxine-8-carboxamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-2-(tetrahydro-2H-pyran-4-yl)acetamide;

trans-(+/−

)-4-chloro-2,5-difluoro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-indole-6-carboxamide;

trans-(+/−

)-3-(1H-1,2,3-benzotriazol-1-yl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-3-(2-thienyl)propanamide;

trans-(+/−

)-2-(1-benzofuran-4-yl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-4-(dimethylamino)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-3-pyridin-3-ylpropanamide;

trans-(+/−

)-4,6-dimethyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]nicotinamide;

trans-(+/−

)-3-(5-methyl-2-furyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-pyrazole-5-carboxamide;

trans-(+/−

)-2-cyclopropyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-5-methoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1-benzofuran-2-carboxamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-indazole-3-carboxamide;

trans-(+/−

)-6-(ethylthio)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]nicotinamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-4-(1H-pyrrol-1-yl)benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-indole-4-carboxamide;

trans-(+/−

)-2-chloro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-3-cyano-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-2-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide;

trans-(+/−

)-3-chloro-4-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]thiophene-2-carboxamide;

trans-(+/−

)-3-(5-methyl-1H-pyrazol-1-yl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-3-methoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-2-(2,3-dihydro-1-benzofuran-5-yl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1,3-benzodioxole-5-carboxamide;

trans-(+/−

)-5-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]thiophene-2-carboxamide;

trans-(+/−

)-1-ethyl-5-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-1H-pyrazole-4-carboxamide;

trans-(+/−

)-5-ethoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-2-furamide;

trans-(+/−

)-3-(4-fluorophenoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]propanamide;

trans-(+/−

)-3-fluoro-4-methoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-4-propylbenzamide;

trans-(+/−

)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]hexanamide;

trans-(+/−

)-4-butoxy-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-chloro-2-fluoro-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-2-oxo-N-[2-(piperidin-1-ylmethyl)cyclohexyl]-2,3-dihydro-1H-benzimidazole-5-carboxamide;

trans-(+/−

)-2-(4-ethoxyphenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]acetamide;

trans-(+/−

)-3-phenyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]isoxazole-5-carboxamide;

trans-(+/−

)-2-methoxy-5-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-4-methoxy-N-{2-[(4-phenylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-N-[2-(1,4-dioxa-8-azaspiro[4,5]dec-8-ylmethyl)cyclohexyl]-4-methoxybenzamide;

trans-(+/−

)-N-{2-[(3,5-dimethylpiperidin-1-yl)methyl]cyclohexyl}-4-methoxybenzamide;

trans-(+/−

)-N-{2-[(4-fluoropiperidin-1-yl)methyl]cyclohexyl}-4-methoxybenzamide;

trans-(+/−

)-4-methoxy-N-(2-{[4-(trifluoromethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

trans-(+/−

)-4-methoxy-N-{2-[(4-methoxypiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-4-methoxy-N-(2-{[3-(trifluoromethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

trans-(+/−

)-4-methoxy-N-{2-[(3-phenylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-N-[2-({3-[(allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-methoxybenzamide;

trans-(+/−

)-N-[2-({3-[(allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[3-(methoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(3-pentylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(3-pentylpiperidin-1-yl)methyl]cyclohexyl}-4-(1H-pyrazol-1-yl)benzamide;

trans-(+/−

)-6-(1H-imidazol-1-yl)-N-{2-[(3-pentylpiperidin-1-yl)methyl]cyclohexyl}nicotinamide;

trans-(+/−

)-N-{2-[(3-pentylpiperidin-1-yl)methyl]cyclohexyl}-6-pyrrolidin-1-ylnicotinamide;

trans(±

)-6-(1H-imidazol-1-yl)-N-(2-{[(3R)-3-pentylpiperidin-1-yl]methyl}cyclohexyl)nicotinamide;

trans(±

)-6-(1H-imidazol-1-yl)-N-(2-{[(3S)-3-pentylpiperidin-1-yl]methyl}cyclohexyl)nicotinamide;

trans-(+/−

)-N-{(2-[(3-hexylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(3-hexylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(3-hexylpiperidin-1-yl)methyl]cyclohexyl}-4-(1H-pyrazol-1-yl)benzamide;

trans-(+/−

)-N-{2-[(3-hexylpiperidin-1-yl)methyl]cyclohexyl}-4-pyrrolidin-1-ylbenzamide;

trans-(+/−

)-N-{(2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-4-pyrrolidin-1-ylbenzamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-4-(1H-pyrazol-1-yl)benzamide;

cis-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[4-(Allyloxy)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-[2-({4-[(2E)-But-2-en-1-yloxy]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-pyrrolidin-1-ylnicotinamide;

trans-(+/−

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-(1H-pyrazol-1-yl)benzamide;

trans-(+/−

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-imidazol-1-yl)nicotinamide;

trans-(±

)-N-2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-bromobenzamide;

Trans-(±

)-(N-2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-3-(4-chlorophenyl)propanamide

Trans-(±

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-3-(2-methoxyphenyl)propanamide

Trans-(±

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-cyanobenzamide

Trans-(±

)-N-[(2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-fluorobenzamide

Trans-(±

)-N-[(2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-chlorobenzamide

Trans-(±

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-[(diethylamino)methyl]benzamide

Trans-(±

)-N-[2-({3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide;

trans(±

)-[2-({(3R)-3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-imidazol-1-yl)nicotinamide;

trans(±

)-[2-({(3S)-3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(4-benzylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(4-cyclopentylpiperazin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[methyl(2-phenylethyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-6-(1H-pyrazol-1-yl)-N-(2-{[4-(pyridin-4-ylmethyl)piperazin-1-yl]methyl}cyclohexyl)nicotinamide;

trans-(+/−

)-N-(2-{[methyl(pyridin-3-ylmethyl-)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[(4-ethylbenzyl)(methyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[methyl(1-methylpyrrolidin-3-yl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[methyl(3-methylbutyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[methyl(propyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[benzyl(methyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-{2-[(4-propylpiperidin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[2-(methoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[butyl(methyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[butyl(ethyl)amino]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

trans-(+/−

)-6-(1H-pyrazol-1-yl)-N-(2-{[2-(3-thienylmethyl)piperidin-1-yl]methyl}cyclohexyl)nicotinamide;

trans-(+/−

)-N-{2-[(4,4-difluoropiperidin-1-yl)methyl]cyclohexyl}-4-methoxybenzamide;

trans-(+/−

)-4-methoxy-N-{2-[(4-methylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-4-(2-methoxyethoxy)-N-{2-[(4-methylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-4-methoxy-N-[2-(morpholin-4-ylmethyl)cyclohexyl]benzamide;

cis-(+/−

)-4-(2-ethoxyethoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

cis-(+/−

)-4-(2-ethoxyethoxy)-N-[2-(pyrrolidin-1-ylmethyl)cyclohexyl]benzamide;

cis-(+/−

)-N-{2-[(diethylamino)methyl]cyclohexyl}-4-(2-ethoxyethoxy)benzamide;

trans-(+/−

)-4-(2-ethoxyethoxy)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzamide;

trans-(+/−

)-N-[2-(azepan-1-ylmethyl)cyclohexyl]-4-(2-ethoxyethoxy)benzamide;

trans-(+/−

)-N-{2-[(diethylamino)methyl]cyclohexyl}-4-(2-ethoxyethoxy)benzamide;

trans-(+/−

)-N-(4-chlorophenyl)-N′

-[2-(piperidin-1-ylmethyl)cyclohexyl]urea;

trans-(+/−

)-N-(4-cyanophenyl)-N′

-[2-(piperidin-1-ylmethyl)cyclohexyl]urea;

trans-(+/−

)-N-(4-methoxyphenyl)-N′

-[2-(piperidin-1-ylmethyl)cyclohexyl]urea;

trans-(+/−

)-2-methoxy-4-methyl-N-[2-(piperidin-1-ylmethyl)cyclohexyl]benzenesulfonamide;

trans-(+/−

)-methyl 3-({[2-(piperidin-1-ylmethyl)cyclohexyl]amino}sulfonyl)thiophene-2-carboxylate;

trans-(+/−

)-5-[2-(methylthio)pyrimidin-4-yl]-N-[2-(piperidin-1-ylmethyl)cyclohexyl]thiophene-2-sulfonamide;

trans-(+/−

)-1-(4-chlorophenyl)-N-[2-(piperidin-1-ylmethyl)cyclohexyl]methanesulfonamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-4-(1,3-oxazol-5-yl)benzamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-6-(trifluoromethyl)nicotinamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-4-(2-methoxyethoxy)benzamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-3-(4-chlorophenyl)propanamide;

trans-(+/−

)-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}-4-(1H-imidazol-1-yl)benzamide;

trans-(+/−

)-N-(2-{[3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-N-(2-{[3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-(1,3-oxazol-5-yl)benzamide;

trans-(+/−

)-N-(2-{[3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-imidazol-1-yl)benzamide;

trans-(+/−

)-N-2-{[3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-{[(methylsulfonyl)amino]methyl}benzamide;

trans-(+/−

)-N-(2-{[3-propylpiperidin-1-yl]methyl}cyclohexyl)-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-4-(1H-imidazol-1-yl)-N-{2-[(3-propylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-N-(2-{[3-isobutylpiperidin-1-yl]methyl}cyclohexyl)-6-(1H-imidazol-1-yl)nicotinamide;

trans-(+/−

)-4-(1H-imidazol-1-yl)-N-{2-[(3-isobutylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-4-Bromo-N-{2-[(3-propylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-3-(4-Chlorophenyl)-N-{2-[(3-propylpiperidin-1-yl)methyl]cyclohexyl}propanamide;

trans-(+/−

)-4-Bromo-N-{2-[(3-butylpiperidin-1-yl)methyl]cyclohexyl}benzamide;

trans-(+/−

)-N-{2-[(3-Butylpiperidin-1-yl)methyl]cyclohexyl}-4-[(diethylamino)methyl]benzamide;

trans-(+/−

)-3-(4-Chlorophenyl)-N-(2-{[3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)propanamide;

N-[(1S,2R)-2-({4-[(2E)-But-2-en-1-yloxy]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

N-{(1S,2R)-2-[(4-Butoxypiperidin-1-yl)methyl]cyclohexyl}-6-(1H-pyrazol-1-yl)nicotinamide;

N-(1S,2R)-2-{[(3R)-3-(2-Methoxyethoxy)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-pyrazol-1-yl)benzamide;

N-(1R,2S)-2-{[(3R)-3-(2-Methoxyethoxy)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-pyrazol-1-yl)benzamide;

N-[(1S,2R)-2-({(3R)-3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

N-[(1R,2S)-2-({(3R)-3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

N-[(1R,2S)-2-({(3R)-3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide

N-[(1S,2R)-2-({(3R)-3-[(Allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-imidazol-1-yl)nicotinamide;

(N-((1S,2R)-2-{[(3R)-3-ethoxypiperidin-1-yl]methyl}cyclohexyl)pyrazine-2-carboxamide;

N-((1S,2R)-2-{[(3R)-3-ethoxypiperidin-1-yl]methyl}cyclohexyl)-6-(ethylthio)nicotinamide;

N-((1S,2R)-2-{[(3R)-3-ethoxypiperidin-1-yl]methyl}cyclohexyl)-6-pyrrolidin-1-ylnicotinamide;

N-[(1S,2R)-2-(azepan-1-ylmethyl)cyclohexyl]-4-(1H-pyrazol-1-yl)benzamide;

N-[(1S,2R)-2-(azepan-1-ylmethyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

N-((1S,2R)-2-{[(3R)-3-(allyloxy)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-pyrazol-1-yl)benzamide;

N-((1R,2S)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-pyrrol-1-yl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-pyrrol-1-yl)benzamide;

N-((1R,2S)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-6-pyrrolidin-1-ylnicotinamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-6-pyrrolidin-1-ylnicotinamide;

N-[(1S,2R)-2-(piperidin-1-ylmethyl)cyclohexyl]-4-(1H-pyrazol-1-yl)benzamide;

N-[(1S,2R)-2-(piperidin-1-ylmethyl)cyclohexyl]-6-(1H-pyrazol-1-yl)nicotinamide;

N-((1S,2R)-2-{[(3R)-3-(allyloxy)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-pyrrol-1-yl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(allyloxy)piperidin-1-yl]-methyl}cyclohexyl)-3-cyclopentylpropanamide;

N-((1S,2R)-2-{[(3R)-3-(allyloxy)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

N-((1S,2R)-2-{[(3S)-3-(allyloxy)piperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

N-((1S,2R)-2-{[(3S)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclo-hexyl)-4-(2-methoxyethoxy)benzamide;

3-(4-chlorophenyl)-N-((1S,2R)-2-{[(3S)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)propanamide;

N-((1S,2R)-2-{[(3S)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclo-hexyl)-4-{[(methylsulfonyl)amino]methyl}benzamide;

4-[(diethylamino)methyl]-N-((1S,2R)-2-{[(3S)-3-(ethoxymethyl)-piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-[(1S,2R)-2-({(3R)-3-[(allyloxy)methyl]piperidin-1-yl}methyl)cyclohexyl]-6-(1H-imidazol-1-yl)nicotinamide;

4-chloro-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)cyclohexanecarboxamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-2-phenylacetamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-3-phenylpropanamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-2,3-dihydro-1-benzofuran-5-carboxamide;

2-cyclopentyl-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)acetamide;

2-chloro-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-3-fluoroisonicotinamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)chromane-2-carboxamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4,6-dimethylnicotinamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide hydrochloride salt;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-2-(3-methoxyphenyl)acetamide;

2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)acetamide hydrochloride salt;

N2-acetyl-N1-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)glycinamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-2-(1H-tetrazol-1-yl)acetamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-2-carboxamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-3,4-dihydro-2H-1,5-benzodioxepine-6-carboxamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-methyl-3,4-dihydro-2H-1,4-benzoxazine-7-carboxamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-5-phenyl-1H-pyrazole-4-carboxamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-(1H-tetrazol-1-yl)benzamide;

4-[(diethylamino)methyl]-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-(2-methoxyethoxy)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-{[(methylsulfonyl)amino]methyl}benzamide;

4-[(acetylamino)methyl]-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

4-[(diacetylamino)methyl]-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-{[(ethylsulfonyl)amino]methyl}benzamide;

4-{[(cyclopropylsulfonyl)amino]methyl}-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-({[(methylamino)carbonyl]amino}methyl)benzamide;

4-({[(dimethylamino)carbonyl]amino}methyl)-N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)benzamide;

N-((1S,2R)-2-{[(3R)-3-(ethoxymethyl)piperidin-1-yl]methyl}cyclohexyl)-4-[(isobutyrylamino)methyl]benzamide;

N-((1S,2R)-2-{[3-cyclohexylpiperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

N-((1S,2R)-2-{[3-phenylpiperidin-1-yl]methyl}cyclohexyl)-6-(1H-pyrazol-1-yl)nicotinamide;

and pharmaceutically acceptable salts thereof.

14. A pharmaceutical composition comprising a compound according to claim 7 and a pharmaceutically acceptable carrier.

17. A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 7.

20. A method for the therapy of Alzheimer'"'"'s disease in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 7.

23. A method for the therapy of schizophrenia in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 7.

29. A method for the therapy of anxiety in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 7.

32. A method for the therapy of depression in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 7.

8. A compound of formula V, a pharmaceutically acceptable salt thereof, diastereomer, enantiomer, or mixture thereof:

wherein

R¹ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl, wherein said C_6-10aryl, C_2-9heteroaryl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl are optionally substituted with one or more group selected from C_6-10aryl, C_1-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

O(CH₂)_m—

OR, R, —

C(═

O)—

R, —

CO₂R, —

SO₂R, —

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, —

(CH₂)_mNHC(═

O)—

NR₂, —

NHC(═

O)—

R, —

N[C(═

O)R]₂, —

(CH₂)_mNHC(═

O)—

R, —

(CH₂)_mN[C(═

O)—

R]₂—

(CH₂)_mNHS(═

O)₂—

R, and —

C(═

O)—

NR₂; and

R⁴ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

(CH₂)_mOR, —

O(CH₂)_mOR, —

O(CH₂)_mNR₂, —

(CH₂)_m—

O—

(CH₂)_mOR, —

(CH₂)_m—

O—

(CH₂)_nNR₂, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂;

each R is independently hydrogen, C_1-6alkyl, C_2-6alkenyl or halogenated C_1-6alkyl;

with a proviso that

R¹ is not 4-amino-5-chloro-2-alkoxylphenyl, 4-amino-5-chloro-2-cycloalkoxyphenyl, 4-amino-5-chloro-2-cycloalkyl-alkoxy-phenyl, 4-butoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-isobutoxyphenyl, 4-benzoyloxyphenyl and 7-(2,3-dihydro)benzofuranyl.

9. A compound as claimed in claim 8, wherein

R¹ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_3-6alkyl, wherein said C_6-10aryl, C_2-9heteroaryl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_3-6alkyl are optionally substituted by one or more groups selected from 1H-pyrazol-1-yl, fluoro, chloro, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, t-butyl, cyano, bromo, 1,3-oxazol-5-yl, 1H-imidazol-1-yl, (4-oxopiperidin-1-yl)carbonyl, pyridin-3-ylmethyl, [(butylamino)carbonyl]amino, 1,1-dioxidothiomorpholin-4-yl, aminosulfonyl, morpholin-4-yl, diethylaminomethyl, acetyl, (3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methyl, 1-oxo-indan-4-yl, dimethylaminomethyl, methyl, pyrrolidin-1-yl, ethylthio, acetylamino, dimethylamino, 1H-pyrrol-1-yl, ethyl, ethoxy, fluorophenoxy, propyl, phenyl, methoxycarbonyl, diacetylamino, (methylsulfonylamino)methyl, (cyclopropylsulfonylamino)methyl, 1H-tetrazol-1-yl, pyrazolyl, methylaminocarbonylamino, dimethylaminocarbonylamino, and (methylthio)pyrimidin-4-yl.

10. A compound as claimed in claim 8, wherein said R¹ is selected from 2-cyclopentylethyl, cyclopropylmethyl, ethyl, methyl, cyclohexyl, cyclopentylmethyl, chromanyl, pentyl, 2-phenylethyl, phenyl, benzyl, pyridinyl, pyridinylethyl, 1-benzofuranyl, benzothienyl, furyl, imidazolyl, pyrazolo[1,5-a]pyrimidinyl, pyrazinyl, 1,3-benzothiazolyl, indolyl, indazolyl, thienyl, 1,3-benzodioxinyl, tetrahydro-2H-pyran-4-ylmethyl, 1-H-1,2,3-benzotriazol-1-yl, 2-(thien-2-yl)ethyl, (1-benzofuran-4-yl)methyl, 1,3-oxazolyl, 1H-pyrazol-1-yl, 2,3-dihydro-1-benzofuran-5-yl, 1,3-benzodioxol-5-yl, 2-oxo-2,3-dihydro-2H-benzimidazolyl, isoxazolyl, imidazo[1,2,a]pyridinyl, 2-3-dioxo-2,3-dihydro-1H-indol-1-yl, 3,4-dihydro-2H-1,4-benzoxazinyl;

pyrazolyl, 1H-tetrazol-1-yl-methyl, and 3,4-dihydro-2H-1,5-benzodioxepinyl, which are optionally substituted by one or more groups selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

O(CH₂)_m—

OR, R, —

C(═

O)—

R, —

CO₂R, —

SO₂R, —

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, —

(CH₂)_mNHC(═

O)—

NR₂, —

NHC(═

O)—

R, —

N[C(═

O)R]₂, —

(CH₂)_mNHC(═

O)—

R—

(CH₂)_mN[C(═

O)—

R]₂—

(CH₂)_mNHS(═

O)₂—

R, and —

C(═

O)—

NR₂.

11. A compound as claimed in claim 8, wherein said R¹ is selected from 2-cyclopentylethyl, cyclopropylmethyl, ethyl, methyl, cyclohexyl, cyclopentylmethyl, chromanyl, pentyl, 2-phenylethyl, phenyl, benzyl, pyridinyl, pyridinylethyl, 1-benzofuranyl, benzothienyl, furyl, imidazolyl, pyrazolo[1,5-a]pyrimidinyl, pyrazinyl, 1,3-benzothiazolyl, indolyl, indazolyl, thienyl, 1,3-benzodioxinyl, tetrahydro-2H-pyran-4-ylmethyl, 1-H-1,2,3-benzotriazol-1-yl, 2-(thien-2-yl)ethyl, (1-benzofuran-4-yl)methyl, 1,3-oxazolyl, 1H-pyrazol-1-yl, 2,3-dihydro-1-benzofuran-5-yl, 1,3-benzodioxol-5-yl, 2-oxo-2,3-dihydro-2H-benzimidazolyl, isoxazolyl, imidazo[1,2,a]pyridinyl, 2-3-dioxo-2,3-dihydro-1H-indol-1-yl, 3,4-dihydro-2H-1,4-benzoxazinyl;

pyrazolyl, 1H-tetrazol-1-yl-methyl, and 3,4-dihydro-2H-1,5-benzodioxepinyl, which are optionally substituted by are optionally substituted by one or more groups selected from 1H-pyrazol-1-yl, fluoro, chloro, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, t-butyl, cyano, bromo, 1,3-oxazol-5-yl, 1H-imidazol-1-yl, (4-oxopiperidin-1-yl)carbonyl, pyridin-3-ylmethyl, [(butylamino)carbonyl]amino, 1,1-dioxidothiomorpholin-4-yl, aminosulfonyl, morpholin-4-yl, diethylaminomethyl, acetyl, (3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)methyl, 1-oxo-indan-4-yl, dimethylaminomethyl, methyl, pyrrolidin-1-yl, ethylthio, acetylamino, dimethylamino, 1H-pyrrol-1-yl, ethyl, ethoxy, fluorophenoxy, propyl, phenyl, methoxycarbonyl, diacetylamino, (methylsulfonylamino)methyl, (cyclopropylsulfonylamino)methyl, 1H-tetrazol-1-yl, pyrazolyl, methylaminocarbonylamino, dimethylaminocarbonylamino, and (methylthio)pyrimidin-4-yl.

12. A compound as claimed in claim 8, wherein

R⁴ is selected from phenyl, benzyl, methyl, fluoro, trifluoromethyl, methoxy, allyloxy, (2E)-but-2-en-1-yloxy, (allyloxy)methyl, methoxymethyl, ethoxymethyl, propyl, butyl, pentyl, hexyl, cyclopentyl, pyridin-4-ylmethyl, ethoxy, butoxy, 2-methoxyethoxy, cyclohexyl, and thienylmethyl.

15. A pharmaceutical composition comprising a compound according to claim 8 and a pharmaceutically acceptable carrier.

18. A method for the therapy of pain in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 8.

21. A method for the therapy of Alzheimer'"'"'s disease in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 8.

24. A method for the therapy of schizophrenia in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 8.

30. A method for the therapy of anxiety in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 8.

33. A method for the therapy of depression in a warm-blooded animal, comprising the step of administering to said animal in need of such therapy a therapeutically effective amount of a compound according to claim 8.

25. A process for preparing a compound of Formula II, comprising:

reacting a compound of Formula III with a compound of R¹—

COCl or R¹—

COOH,

wherein

R¹ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl, wherein said C_6-10aryl, C_2-9heteroaryl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl are optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

O(CH₂)_m—

OR, R, —

C(═

O)—

R, —

CO₂R, —

SO₂R, —

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, —

(CH₂)_mNHC(═

O)—

NR₂—

NHC(═

O)—

R, —

N[C(═

O)R]₂, —

(CH₂)_mNHC(═

O)—

R, —

(CH₂)_mN[C(═

O)—

R]₂—

(CH₂)_mNHS(═

O)₂—

R, and —

C(═

O)—

NR₂;

R² and R³ are independently selected from C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy wherein said C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy are optionally substituted by one or more groups selected from amino, halogen, C_1-6alkoxy and —

CN;

or R² and R³ together with the nitrogen connected thereto form a heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

(CH₂)_mOR, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂;

each R is independently hydrogen, C_1-6alkyl, C_2-6alkenyl or halogenated C_1-6alkyl; and

with a proviso that

when R² and R³ together with the nitrogen connected thereto form said piperidinyl;

R¹ is not 4-amino-5-chloro-2-alkoxylphenyl, 4-amino-5-chloro-2-cycloalkoxyphenyl, 4-amino-5-chloro-2-cycloalkyl-alkoxy-phenyl, 4-butoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-isobutoxyphenyl, 4-benzoyloxyphenyl and 7-(2,3-dihydro)benzofuranyl.

26. A process for preparing a compound of Formula IV, comprising:

reacting a compound of Formula III with a compound of R¹SO₂Cl,

wherein

R¹ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl, wherein said C_6-10aryl, C_2-9heteroaryl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl are optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

O(CH₂)_m—

OR, R, —

C(═

O)—

R, —

CO₂R, —

SO₂R, —

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, —

(CH₂)_mNHC(═

O)—

NR₂—

NHC(═

O)—

R, —

N[C(═

O)R]₂, —

(CH₂)_mNHC(═

O)—

R, —

(CH₂)_mN[C(═

O)—

R]₂—

(CH₂)_mNHS(═

O)₂—

R, and —

C(═

O)—

NR₂;

R² and R³ are independently selected from C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy wherein said C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy are optionally substituted by one or more groups selected from amino, halogen, C_1-6alkoxy and —

CN;

or R² and R³ together with the nitrogen connected thereto form a heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

(CH₂)_mOR, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂; and

each R is independently hydrogen, C_1-6alkyl, C_2-6alkenyl or halogenated C_1-6alkyl.

27. A process for preparing a compound of Formula VI, comprising

reacting a compound of Formula III with R¹NCO,

wherein

R¹ is selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl, wherein said C_6-10aryl, C_2-9heteroaryl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-3alkyl, and C_1-6alkyl are optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_6-10aryl-O—

C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

O(CH₂)_m—

OR, R, —

C(═

O)—

R, —

CO₂R, —

SO₂R, —

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, —

(CH₂)_mNHC(═

O)—

NR₂—

NHC(═

O)—

R, —

N[C(═

O)R]₂, —

(CH₂)_mNHC(═

O)—

R, —

(CH₂)_mN[C(═

O)—

R]₂—

(CH₂)_mNHS(═

O)₂—

R, and —

C(═

O)—

NR₂;

R² and R³ are independently selected from C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy wherein said C_1-6alkyl, C_2-6alkenyl, and C_1-6alkoxy are optionally substituted by one or more groups selected from amino, halogen, C_1-6alkoxy and —

CN;

or R² and R³ together with the nitrogen connected thereto form a heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more group selected from C_6-10aryl, C_2-9heteroaryl, C_3-6cycloalkyl, C_3-5heterocycloalkyl, C_6-10aryl-C_1-3alkyl, C_2-9heteroaryl-C_1-3alkyl, C_3-5heterocycloalkyl-C_1-3alkyl, —

CN, —

SR, —

OR, —

(CH₂)_mOR, R, —

CO₂R;

—

SO₂R;

—

SO₂NR₂, halogen, —

NO₂, —

NR₂, —

(CH₂)_mNR₂, and —

C(═

O)—

NR₂; and

each R is independently hydrogen, C_1-6alkyl, C_2-6alkenyl or halogenated C_1-6alkyl.