Vanilloid receptor ligands and their use in treatments
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Abstract
Compounds having the general structure
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Citations
94 Claims
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1. A compound having the structure:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 71, 72, 92)
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2. A compound according to claim 1, wherein:
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R1 is R2 is H, hydroxy, halo, C1-6alkyl 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 C1-4alkyl.
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3. A compound according to claim 1, wherein R7 is independently, at each instance, C2-9alkyl or C1-4haloalkyl.
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4. A compound according to claim 2, wherein R2 is
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5. A compound according to claim 4, wherein R2 is
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6. A compound according to claim 4, 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.
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7. A compound according to claim 1, wherein R1 and R2 together are
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8. A compound according to claim 1, wherein R1 and R3 together are
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9. A compound according to claim 2, wherein:
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R4 is Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRa—
or —
O—
.
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10. A compound according to claim 2, wherein:
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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, —
ORa, —
C1-6alkylORa, —
C1-6alkyl, —
NRaRa, —
C1-6alkylNRaRa, —
C(═
)ORa, —
C(═
R)NRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
OC(═
)C1-6alkyl, —
NRaC(═
O)C1-6alkyl, —
C1-3alkylOC(═
O)C1-6alkyl or —
C1-3alkylNRaC(═
C)C1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —
C1-6alkylORa —
C1-6alkyl, —
C1-6alkylNRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
C1-3alkylOC(═
O)C1-6alkyl, —
C1-3alkylNRaC(═
O)C1-6alkyl, —
C(═
O)Rc or —
C1-3alkylRc;
Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRb—
or —
O—
.
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11. A compound according to claim 2, wherein:
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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, —
ORa, —
C1-6alkylORa, —
C1-6alkyl, —
NRaRa, —
C1-6alkylNRaRa, —
C(═
O)ORa, —
C(═
O)NRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
OC(═
O)C1-6alkyl, —
NRaC(═
O)C1-6alkyl, —
C1-3alkylOC(═
O)C1-6alkyl or —
C1-3alkylNRaC(═
O)C1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —
C1-6alkylORa, —
C1-6alkyl, —
C1-6alkylNRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
C1-3alkylOC(═
O)C1-6alkyl, —
C1-3alkylNRaC(═
O)C1-6alkyl, —
C(═
O)Rc or —
C1-3alkylRc;
Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRb—
or —
O—
.
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12. A compound according to claim 2, wherein:
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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, —
ORa, —
C1-6alkylORa, —
C1-6alkyl, —
NRaRa, —
C1-6alkylNRaRa, —
C(═
O)ORa, —
C(═
O)NRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
OC(═
O)C1-6alkyl, —
NRaC(═
O)C1-6alkyl, —
C1-3alkylOC(═
O)C1-6alkyl or —
C1-3alkylNRaC(═
O)C1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —
C1-6alkylORa, —
C1-6alkyl, —
C1-6alkylNRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
C1-3alkylOC(═
O)C1-6alkyl, —
C1-3alkylNRaC(═
O)C1-6alkyl, —
C(═
O)Rc or —
C1-3alkylRc;
Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRb—
or —
O—
.
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13. A compound according to claim 2, wherein:
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R4 is Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRa—
or —
O—
.
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14. 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, ORa, NRaRa, C1-6alkyl and C1-3haloalkyl; and
saturated carbon atoms may be additionally substituted by ═
O.
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15. A compound according to claim 2, wherein:
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R4 is R10 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
R11 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylRc, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
C1-6alkylNRaRa;
R12 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
R13 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl; and
R14 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, NRaRa, —
NRaC1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
wherein one of R10 and R12 is not H.
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16. 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, C1-4haloalkyl, —
- ORa and —
NRaRa.
- ORa and —
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71. A compound according to claim 1, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:
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(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-enoylamino}-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-[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)(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)-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-[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.
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72. A compound according to claim 1, or a pharmaceutically-acceptable salt thereof, wherein the compounds is selected from:
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92. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically-acceptable diluent or carrier.
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2. A compound according to claim 1, wherein:
-
17. A compound having the structure:
- View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 61, 90, 93)
-
18. A compound according to claim 17, wherein:
-
R1 is R2 is H, —
ORm, halo, C1-3haloalkyl or C1-6alkyl;
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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)OR5, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm; and
the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups;
R7 is C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Ro 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 Rp;
Rp is independently at each instance C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm or —
NRmC2-6alkylORm; and
Y is O or NH.
-
-
19. A compound according to claim 18, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmR5, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm; and
the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups.
-
20. A compound according to claim 18, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)Orn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2R5, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm; and
the bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups.
- C(═
-
21. A compound according to claim 18, wherein R7 is C1-9alkyl, C1-4haloalkyl, halo, —
- OC1-6alkyl, —
O—
C1-4haloalkyl, —
NRmRm or —
NRm—
C1-4haloalkyl.
- OC1-6alkyl, —
-
22. A compound according to claim 18, wherein R7 is C1-5alkyl, C1-4haloalkyl, I, Br or Cl.
-
23. A compound according to claim 18, wherein R7 is tert-butyl or trifluoromethyl.
-
24. A compound according to claim 18, wherein Ro 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 Rp.
-
25. A compound according to claim 18, wherein Ro 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 Rp.
-
26. A compound according to claim 18, wherein Y is O.
-
27. A compound according to claim 18, wherein Y is NH.
-
28. A compound according to claim 17, wherein:
-
R1 is R2 is H, —
ORm, halo, C1-3haloalkyl or C1-6alkyl;
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 C1-9alkyl, oxo, C1-4haloalkyl, halo, nitro, cyano, —
ORm, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm, —
NRm—
C1-6alkylORm, —
C(═
O)C1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRmC1-6alkyl, —
NRmC(═
O)C1-6alkyl —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2R5, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm;
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 C1-8alkyl, C1-5haloalkyl, I or Br;
R9 is H, C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Y is NH; and
Z is CR8.
-
-
29. A compound according to claim 28, 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 C1-9alkyl, oxo, C1-4haloalkyl, halo, nitro, cyano, —
- ORm, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm, —
NRm—
C1-6alkylORm, —
C(═
O)C1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRmC1-6alkyl, —
NRmC(═
O)C1-6alkyl —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2R5, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm.
- ORm, —
-
30. A compound according to claim 28, 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 C1-9alkyl, oxo, C1-4haloalkyl, halo, nitro, cyano, —
- ORm, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm, —
NRm—
C1-6alkylORm, —
C(═
O)C1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRmC1-6alkyl, —
NRmC(═
O)C1-6alkyl —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm.
- ORm, —
-
31. A compound according to claim 28, wherein R9 is C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
- OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm.
- OC1-6alkyl, —
-
32. A compound according to claim 28, wherein R9 is H.
-
33. A compound according to claim 28, wherein R7 is tert-butyl or trifluoromethyl.
-
34. A compound according to claim 17, wherein:
-
R1 is R2 is C1-6alkyl substituted by 1, 2 or 3 substituents selected from C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
orR2 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm, and the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups;
R7 is C2-8alkyl, C1-5haloalkyl, I, Br;
R9 is independently, at each instance, H, C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Y is NH; and
Z is CR8.
-
-
35. A compound according to claim 34, wherein R2 is C1-6alkyl substituted by 1, 2 or 3 substituents selected from C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rm, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm. —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
- C(═
-
36. A compound according to claim 34, wherein R2 is —
- (C(Rq)2)ophenyl, wherein the phenyl is substituted by 0, 1, 2 or 3 substituents independently selected from C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(=O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm.
- (C(Rq)2)ophenyl, wherein the phenyl is substituted by 0, 1, 2 or 3 substituents independently selected from C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
-
37. A compound according to claim 34, wherein R2 is —
- (C(Rq)2)oRr, wherein Rr 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm;
- (C(Rq)2)oRr, wherein Rr 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
-
38. A compound according to claim 34, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm; and
the bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups.
- C(═
-
39. A compound according to claim 34, wherein R7 is tert-butyl or trifluoromethyl.
-
40. A compound according to claim 34, wherein R9 is H.
-
41. A compound according to claim 17, wherein:
-
R1 is R2 is H, —
ORm, Cl, C1-3haloalkyl or C1-6alkyl;
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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORn, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylORm, —
SRm, —
S(═
O)Ra, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2R , —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
C)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rm, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
wherein R4 is not unsubstituted phenyl;
R9 is independently, at each instance, H, C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Y is NH; and
Z is CR8.
-
-
42. A compound according to claim 41, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORn, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORS, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
C)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
- C(═
-
61. A compound according to claim 28, wherein R7 is tert-butyl or trifluoromethyl.
-
90. 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 17.
-
93. A pharmaceutical composition comprising a compound according to claim 17 and a pharmaceutically acceptable diluent or carrier.
-
18. A compound according to claim 17, wherein:
-
43. A compound having the structure:
- View Dependent Claims (44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 91, 94)
-
44. A compound according to claim 43, wherein:
-
R1 is R2 is H, —
ORm, halo, C1-3haloalkyl or C1-6alkyl;
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 C1-9alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRml Rs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm; and
the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups;
R7 is C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Ro 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 Rp;
Rp is independently at each instance C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm or —
NRmC2-6alkylORm; and
Y is O or NH.
-
-
45. A compound according to claim 44, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs—
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm; and
the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups.
-
46. A compound according to claim 44, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRm, Rm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORn, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm; and
the bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups.
- C(═
-
47. A compound according to claim 44, wherein R7 is C1-9alkyl, C1-4haloalkyl, halo, —
- OC1-6alkyl, —
O—
C1-4haloalkyl, —
NRmRm or —
NRm—
C1-4haloalkyl.
- OC1-6alkyl, —
-
48. A compound according to claim 44, wherein R7 is C1-5alkyl, C1-4haloalkyl, I, Br or Cl.
-
49. A compound according to claim 44, wherein R7 is tert-butyl or trifluoromethyl.
-
50. A compound according to claim 44, wherein Ro 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 Rp.
-
51. A compound according to claim 44, wherein Ro 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 Rp.
-
52. A compound according to claim 44, wherein Y is O.
-
53. A compound according to claim 44, wherein Y is NH.
-
54. A compound according to claim 43, wherein:
-
R1 is R2 is H, —
ORm, halo, C1-3haloalkyl or C1-6alkyl;
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 C1-9alkyl, oxo, C1-4haloalkyl, halo, nitro, cyano, —
ORm, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm, —
NRm—
C1-6alkylORm, —
C(═
O)C1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRmC1-6alkyl, —
NRmC(═
O)C1-6alkyl —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm;
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 C1-8alkyl, C1-5haloalkyl, I or Br;
R9 is H, C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Y is NH; and
Z is CR8.
-
-
55. A compound according to claim 54, 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 C1-9alkyl, oxo, C1-4haloalkyl, halo, nitro, cyano, —
- ORm, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm, —
NRm—
C1-6alkylORm, —
C(═
O)C1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRmC1-6alkyl, —
NRmC(═
O)C1-6alkyl —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm.
- ORm, —
-
56. A compound according to claim 54, 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 C1-9alkyl, oxo, C1-4haloalkyl, halo, nitro, cyano, —
- ORm, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm, —
NRm—
C1-6alkylORm, —
C(═
O)C1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRmC1-6alkyl, —
NRmC(═
O)C1-6alkyl —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs, and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs—
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm.
- ORm, —
-
57. A compound according to claim 54, wherein R9 is C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
- OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm.
- OC1-6alkyl, —
-
58. A compound according to claim 54, wherein R9 is H.
-
59. A compound according to claim 54, wherein Z is CR8.
-
60. A compound according to claim 54, wherein Z is N.
-
62. A compound according to claim 43, wherein:
-
R1 is R2 is C1-6alkyl substituted by 1, 2 or 3 substituents selected from C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
orR2 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm, and the ring and bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups;
R7 is C2-8alkyl, C1-5haloalkyl, I, Br;
R9 is independently, at each instance, H, C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Y is NH; and
Z is CR8.
-
-
63. A compound according to claim 62, wherein R2 is C1-6alkyl substituted by 1, 2 or 3 substituents selected from C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
- C(═
-
64. A compound according to claim 62, wherein R2 is —
- (C(Rq)2)ophenyl, wherein the phenyl is substituted by 0, 1, 2 or 3 substituents independently selected from C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm.
- (C(Rq)2)ophenyl, wherein the phenyl is substituted by 0, 1, 2 or 3 substituents independently selected from C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
-
65. A compound according to claim 62, wherein R2 is —
- (C(Rq)2)oRr, wherein Rr 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
OORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and —
NRmC2-6alkylORm;
- (C(Rq)2)oRr, wherein Rr 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
-
66. A compound according to claim 62, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)ORn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm; and
the bridge carbon atoms are substituted with 0, 1 or 2 ═
O groups.
- C(═
-
67. A compound according to claim 62, wherein R7 is tert-butyl or trifluoromethyl.
-
68. A compound according to claim 62, wherein R9 is H.
-
69. A compound according to claim 43, wherein:
-
R1 is R is H, —
ORm, Cl, C1-3haloalkyl or C1-6alkyl;
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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORn, —
C(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
wherein R4 is not unsubstituted phenyl;
R9 is independently, at each instance, H, C1-9alkyl, C1-4haloalkyl, halo, nitro, cyano, —
OC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRmRm, —
O—
C1-6alkylORm, —
NRmRm, —
NRm—
C1-4haloalkyl, —
NRm—
C1-6alkylNRmRm or —
NRm—
C1-6alkylORm;
Y is NH; and
Z is CR8.
-
-
70. A compound according to claim 69, 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 C1-8alkyl, C1-4haloalkyl, halo, cyano, nitro, —
- C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORn, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Rn, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm, —
NRmC2-6alkylORm, —
C(═
O)Rs, —
C(═
O)ORs, —
C(═
O)NRmRs, —
C(═
NRm)NRmRs, —
ORs, —
OC(═
O)Rs, —
OC(═
O)NRmRs, —
OC(═
O)N(Rm)S(═
O)2Rs, —
OC2-6alkylNRmRs, —
OC2-6alkylORs, —
SRs, —
S(═
O)Rs, —
S(═
O)2Rs, —
S(═
O)2NRmRs, —
S(═
O)2N(Rm)C(═
O)Rs, —
S(═
O)2N(Rm)C(═
O)ORs, —
S(═
O)2N(Rm)C(═
O)NRmRs, —
NRmRs, —
N(Rm)C(═
O)Rs, —
N(Rm)C(═
O)ORs, —
N(Rm)C(═
O)NRmRs, —
N(Rm)C(═
NRm)NRmRs, —
N(Rm)S(═
O)2Rs, —
N(Rm)S(═
O)2NRmRs, —
NRmC2-6alkylNRmRs, —
NRmC2-6alkylORs and C1-4alkyl substituted by 1 or 2 groups selected from C1-2haloalkyl, halo, cyano, nitro, —
C(═
O)Rn, —
C(═
O)NRmRm, —
C(═
NRm)NRmRm, —
ORm, —
OC(═
O)Rn, —
OC(═
O)NRmRm, —
OC(═
O)N(Rm)S(═
O)2Rn, —
OC2-6alkylNRmRm, —
OC2-6alkylORm, —
SRm, —
S(═
O)Rn, —
S(═
O)2Rn, —
S(═
O)2NRmRm, —
S(═
O)2N(Rm)C(═
O)Ra, —
S(═
O)2N(Rm)C(═
O)ORn, —
S(═
O)2N(Rm)C(═
O)NRmRm, —
NRmRm, —
N(Rm)C(═
O)Rn, —
N(Rm)C(═
O)ORn, —
N(Rm)C(═
O)NRmRm, —
N(Rm)C(═
NRm)NRmRm, —
N(Rm)S(═
O)2Rn, —
N(Rm)S(═
O)2NRmRm, —
NRmC2-6alkylNRmRm and —
NRmC2-6alkylORm;
- C(═
-
91. 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 43.
-
94. A pharmaceutical composition comprising a compound according to claim 43 and a pharmaceutically acceptable diluent or carrier.
-
44. A compound according to claim 43, wherein:
-
73. 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:
- View Dependent Claims (74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87)
-
74. The method according to claim 73, wherein:
-
R1 is R2 is H, hydroxy, halo, C1-6alkyl 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 C1-4alkyl.
-
-
75. The method according to claim 73, wherein R2 is
-
76. The method according to claim 75, wherein R2 is
-
77. The method according to claim 75, 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.
-
78. The method according to claim 73, wherein R1 and R2 together are
-
79. The method according to claim 73, wherein R1 and R3 together are
-
80. The method according to claim 73, wherein:
-
R4 is Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRa—
or —
O—
.
-
-
81. The method according to claim 73, wherein:
-
R4is 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, —
ORa, —
C1-6alkylORa, —
C1-6alkyl, —
NRaRa, —
C1-6alkylNRaRa, —
C(═
O)ORa, —
C(═
O)NRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
OC(═
O)C1-6alkyl, —
NRaC(═
O)C1-6alkyl, —
C1-3alkylOC(═
O)C1-6alkyl or —
C1-3alkylNRaC(═
O)C1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —
C1-6alkylORa, —
C1-6alkyl, —
C1-6alkylNRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
C1-3alkylOC(═
O)C1-6alkyl, —
C1-3alkylNRaC(═
O)C1-6alkyl, —
C(═
O)Rc or —
C1-3alkylRc;
Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRb—
or —
O—
.
-
-
82. The method according to claim 73, 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, —
ORa, —
C1-6alkylORa, —
C1-6alkyl, —
NRaRa, —
C1-6alkylNRaRa, —
C(═
O)ORa, —
C(═
O)NRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
OC(═
O)C1-6alkyl, —
NRaC(═
O)C1-6alkyl, —
C1-3alkylOC(═
O)C1-6alkyl or —
C1-3alkylNRaC(═
O)C1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —
C1-6alkylORa, —
C1-6alkyl, —
C1-6alkylNRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
C1-3alkylOC(═
O)C1-6alkyl, —
C1-3alkylNRaC(═
O)C1-6alkyl, —
C(═
O)Rc or —
C1-3alkylRc;
Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRb—
or —
O—
.
-
-
83. The method according to claim 73, 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, —
ORa, —
C1-6alkylORa, —
C1-6alkyl, —
NRaRa, —
C1-6alkylNRaRa, —
C(═
O)ORa, —
C(═
O)NRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
OC(═
O)C1-6alkyl, —
NRaC(═
O)C1-6alkyl, —
C1-3alkylOC(═
O)C1-6alkyl or -C1-3alkylNRaC(═
O)C1-6alkyl, and any nitrogen atoms in the bridge are substituted by H, —
C1-6alkylORa, —
C1-6alkyl, —
C1-6alkylNRaRa, —
C1-3alkylC(═
O)ORa, —
C1-3alkylC(═
O)NRaRa, —
C1-3alkylOC(═
O)C1-6alkyl, —
C1-3alkylNRaC(═
O)C1-6alkyl, —
C(═
O)Rc or —
C1-3alkylRc;
Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRb—
or —
O—
.
-
-
84. The method according to claim 73, wherein:
-
R4is Rb is H, C1-6alkyl, —
C(═
O)C1-6alkyl, C1-6alkyl-O—
Ra; and
Y2 is —
NRa—
or —
O—
.
-
-
85. The method according to claim 73, 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, ORa, NRaRa, C1-6alkyl and C1-3haloalkyl;
- and saturated carbon atoms may be additionally substituted by ═
O.
- and saturated carbon atoms may be additionally substituted by ═
-
86. The method according to claim 73, wherein:
-
R4 is R10 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O-C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
R11 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylRc, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
C1-6alkylNRaRa;
R12 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
R13 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl; and
R14 is independently, at each instance, H, C1-9alkyl, —
C1-3alkylORa, C1-4haloalkyl, halo, nitro, cyano, —
ORa, —
S(═
O)nC1-6alkyl, —
O—
C1-4haloalkyl, —
O—
C1-6alkylNRaRa, —
O—
C1-6alkylORa, —
O—
C1-6alkylC(═
O)ORa, —
NRaRa, —
NRa—
C1-4haloalkyl, —
NRa—
C1-6alkylNRaRa, —
NRa—
C1-6alkylORa, —
C(═
O)C1-6alkyl, —
C(═
O)OC1-6alkyl, —
OC(═
O)C1-6alkyl, —
C(═
O)NRaC1-6alkyl or —
NRaC(═
O)C1-6alkyl;
wherein one of R10 and R12 is not H.
-
-
87. The method according to claim 73, wherein R4is 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, C1-4haloalkyl, —
- ORa and —
NRaRa.
- ORa and —
-
74. The method according to claim 73, wherein:
-
88. 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:
-
89. 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:
Specification
- Resources
-
Current AssigneeAmgen Inc.
-
Original AssigneeAmgen Inc.
-
InventorsChen, 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
-
Application NumberUS11/099,978Publication NumberTime in Patent OfficeDaysField of SearchUS Class Current544/236CPC Class CodesA61P 1/00 Drugs for disorders of the ...A61P 1/04 for ulcers, gastritis or re...A61P 1/12 AntidiarrhoealsA61P 11/00 Drugs for disorders of the ...A61P 11/02 Nasal agents, e.g. deconges...A61P 11/06 AntiasthmaticsA61P 13/00 Drugs for disorders of the ...A61P 13/10 of the bladderA61P 17/00 Drugs for dermatological di...A61P 17/02 for treating wounds, ulcers...A61P 17/04 AntipruriticsA61P 17/06 AntipsoriaticsA61P 17/14 for baldness or alopeciaA61P 19/02 for joint disorders, e.g. a...A61P 25/00 Drugs for disorders of the ...A61P 25/02 for peripheral neuropathiesA61P 25/04 Centrally acting analgesics...A61P 25/06 Antimigraine agentsA61P 27/02 Ophthalmic agentsA61P 29/00 Non-central analgesic, anti...A61P 3/10 : for hyperglycaemia, e.g. an...A61P 31/12 : AntiviralsA61P 37/08 : Antiallergic agents antiast...A61P 43/00 : Drugs for specific purposes...A61P 9/00 : Drugs for disorders of the ...C07D 209/08 : with only hydrogen atoms or...C07D 209/12 : Radicals substituted by oxy...C07D 209/42 : Carbon atoms having three b...C07D 209/48 : with oxygen atoms in positi...C07D 213/26 : Radicals substituted by hal...C07D 213/643 : 2-Phenoxypyridines; Derivat...C07D 213/74 : Amino or imino radicals sub...C07D 213/75 : Amino or imino radicals, ac...C07D 215/227 : only one oxygen atom which ...C07D 215/38 : Nitrogen atoms nitro radica...C07D 217/04 : with hydrocarbon or substit...C07D 231/40 : Acylated on said nitrogen atomC07D 231/56 : Benzopyrazoles; Hydrogenate...C07D 233/38 : with acyl radicals or heter...C07D 237/20 : Nitrogen atoms nitro radica...C07D 239/42 : One nitrogen atom nitro rad...C07D 239/90 : with acyclic radicals attac...C07D 241/42 : with only hydrogen atoms, h...C07D 263/56 : with only hydrogen atoms, h...C07D 265/36 : condensed with one six-memb...C07D 277/62 : BenzothiazolesC07D 277/82 : Nitrogen atomsC07D 307/79 : with only hydrogen atoms, h...C07D 319/20 : with substituents attached ...C07D 401/12 : linked by a chain containin...C07D 401/14 : containing three or more he...C07D 403/12 : linked by a chain containin...C07D 405/12 : linked by a chain containin...C07D 407/12 : linked by a chain containin...C07D 409/14 : containing three or more he...C07D 413/12 : linked by a chain containin...C07D 417/12 : linked by a chain containin...C07D 417/14 : containing three or more he...C07D 471/04 : Ortho-condensed systems