Claims
- 1. A compound of Formula I
- 2. A compound of claim 1, wherein R1 and R2, are hydrogen and R3 is oxo.
- 3. A compound of claim 1, wherein R4, R5, R6, and R7 are independently hydrogen, halogen, carboxyl, C1-C3 alkoxy, or C1-C3 alkyl.
- 4. A compound of claim 3, wherein R4, R5, R6, and R7 are independently hydrogen, chlorine, fluorine, carboxyl, methoxy or methyl.
- 5. A compound of claim 1, wherein R4, R6, and R7 are hydrogen and R5 is chlorine, fluorine, carboxyl, methoxy or methyl.
- 6. A compound of claim 1, wherein Q is —NR8—(CH2)0-6—, or —NR9—C(O)—(CH2)0-6— wherein R8 and R9 are independently unsubstituted C1-C3 alkyl.
- 7. A compound of claim 6, wherein Q is —NH—(CH2)0-6—, or —NH—C(O)—(CH2)0-6—.
- 8. A compound of claim 7, wherein Q is —NH—CH2—, —NH—CH2—CH2—, —NH—CH2—CH2—O—CH2—, or —NH—CH2—CH2—O—.
- 9. A compound of claim 1, wherein T is unsubstituted aryl.
- 10. A compound of claim 1, wherein T is unsubstituted phenyl, naphthyl, biphenyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydro-naphthyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinoxalinyl, or 1,2,3,4-tetrahydroindolyl.
- 11. A compound of claim 10, wherein T is 2-naphthyl, biphen-4-yl, 1,2,3,4-tetrahydroquinolin-6-yl, or 1,2,3,4-tetrahydroquinolin-7-yl.
- 12. A compound of claim 1, wherein T is substituted aryl
- 13. A compound of claim 12, wherein T is substituted phenyl, naphthyl, biphenyl, 1,2,3,4-tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydro-naphthyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2,3,4-tetrahydroindolyl, 2,3-dihydroindolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, or 3,4-dihydro-2H-benzo[1,4]oxazinyl.
- 14. A compound of claim 12, wherein T is phenyl substituted from 1 to 5 times with C1-C6alkyl, halo, C1-C6alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—NR16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16—(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16-(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 15. A compound of claim 14, wherein T is 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2-chloro-4-fluorophenyl, 4-fluoro-2-trifluoromethylphenyl, 2-(2-acetoxy-ethyl)-phenyl, 3-(2-acetoxy-ethyl)-phenyl, 4-(2-acetoxy-ethyl)-phenyl, N,N-dimethyl-benzamide-4-yl, or 4-acetylaminophenyl.
- 16. A compound of claim 1, wherein T is biphenyl substituted from 1 to 9 times with C1-C6 alkyl, halo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16—(C_-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl) o—, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl) o—, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR1-S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 17. A compound of claim 1, wherein T is naphthyl, 1,2,3,4-tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydronaphthyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydroindolyl, or 1,2,3,4-tetrahydroindolyl substituted from 1 to 7 times with, C1-C6 alkyl, halo, hydroxy, oxo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)_, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16—(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 18. A compound of claim 17, wherein T is 6-methoxy-2-naphthyl, 7-methoxy-2-naphthyl, 6-methyl-2-naphthyl, 6-hydroxy-2-naphthyl, 7-methyl-2-naphthyl, 6-trifluoromethyl-2-naphthyl, 7-trifluoromethyl-2-naphthyl, 6-fluoro-2-naphthyl, 7-fluoro-2-naphthyl, 6-chloro-2-naphthyl, 7-chloro-2-naphthyl, 6-(2-acetoxy-ethyl)-2-naphthyl, 7-(2-acetoxy-ethyl)-2-naphthyl, 1-(3-hydroxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-acetyl-3,4-dihydro-2H-quinolin-6-yl, 1-(4-thiazolylmethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-7-yl, or 1-(2-acetoxy-ethyl)-3,4-dihydro-2H-quinolin-7-yl.
- 19. A compound of claim 1, wherein T is unsubstituted naphthyl, unsubstituted 4-trifluoromethylphenyl, unsubstituted 1,2,3,4-tetrahydroquinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-5-indolyl, 1-(2-acetylaminoethyl)-5-indolyl, 1-(3-methoxypropyl)-5-indolyl, 1-acetamidyl-5-indolyl, 1-(2-acetoxyethyl)-5-indolyl, 1-(3-methoxy-3-oxopropyl)-5-indolyl, 1-(2-methoxy-2-oxoethyl)-5-indolyl, 1-(2-ethoxy-2-oxoethyl)-6-indolyl, 1-(2-acetylaminoethyl)-6-indolyl, 1-(3-methoxypropyl)-6-indolyl, 1-acetamidyl-6-indolyl, 1-(2-acetoxyethyl)-6-indolyl, 1-(3-methoxy-3-oxopropyl)-6-indolyl, 1-(2-methoxy-2-oxoethyl)-6-indolyl, 4-(2-ethoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(3-methoxypropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-acetylaminoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-acetamidyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-acetoxyethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(3-methoxy-3-oxopropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-methoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 1-(3-hydroxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-hydroxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-acetyl-3,4-dihydro-2H-quinolin-6-yl, 1-acetyl-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(4-thiazolylmethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-6-yl, 1-acetamidyl-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetylaminoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxy-3-oxopropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetylaminoethyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxy-3-oxopropyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(2-ethoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-6-yl, 2-oxo-1,2,3,4-tetrahydro-2H-quinolin-7-yl, 2-oxo-1,2,3,4-tetrahydro-2H-quinolin-6-yl, 1-(2-acetylaminoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxy-3-oxopropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-methoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetylaminoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxy-3-oxopropyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-methoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetoxyethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetoxyethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetoxyethyl)-3,4-dihydro-2H-quinolin-6-yl or 1-(2-acetoxyethyl)-3,4-dihydro-2H-quinolin-7-yl.
- 20. A compound of claim 1, wherein T is unsubstituted heteroaryl.
- 21. A compound of claim 20, wherein T is quinolinyl, indolyl, benzofuryl, isoquinolinyl, pyridyl, pyrimidinyl, pyrazinyl, or quinoxalinyl.
- 22. A compound of claim 21, wherein T is 2-quinolinyl, 6-quinolinyl, 7-quinolinyl, 6-isoquinolinyl, 2-pyridyl, 5-benzofuryl, 2-pyrimidinyl, 2-pyrazinyl, or 2-quinoxalinyl.
- 23. A compound of claim 1, wherein T is substituted heteroaryl.
- 24. A compound of claim 23, wherein T is substituted quinolinyl, indolyl, benzofuryl, isoquinolinyl, pyridyl, pyrimidinyl, pyrazinyl, or quinoxalinyl.
- 25. A compound of claim 24, wherein T is quinolinyl, isoquinolinyl or quinoxalinyl substituted from 1 to 7 times with C1-C6 alkyl, halo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16-(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 26. A compound of claim 24, wherein T is pyridyl, indolyl, pyrimidinyl, or pyrazinyl, substituted from 1 to 5 times with C1-C6 alkyl, halo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16—(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1, (C1-C6 alkyl)-NR16-S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 27. A compound of claim 1, wherein T is N-substituted 1,2,3,4-tetrahydroquinolin-7-yl, N-substituted 1,2,3,4-tetrahydroquinolin-6-yl, N-substituted 2-oxo-1,2,3,4-tetrahydroquinolin-7-yl, N-substituted 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl, N-substituted 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, N-substituted 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl, N-substituted 2-oxo-4a,8a-dihydro-2H-chromen-7-yl, N-substituted 2,3-dihydroindol-6-yl, N-substituted 2-oxo-2,3-dihydroindol-6-yl, N-substituted 2,3-dihydroindol-5-yl, N-substituted 2-oxo-2,3-dihydroindol-5-yl, N-substituted 6-indolyl or N-substituted 5-indolyl.
- 28. A compound of claim 27, wherein the N-substituent is C1-C6 alkyl, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16-(C1-C6 alkyl) ol-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl.
- 29. A compound of claim 1, wherein Z is
- 30. A compound of claim 1, wherein R14 and R15 are hydrogen.
- 31. A compound of claim 1, wherein Z is
—(CH2)0-6—C(O)—NR11—(CH2)0-6— wherein 0 to 6 nonadjacent methylene units are replaced with O, NR12, S or a combination thereof; or —(CH2)0-6—NR11—(C(O)—CH2)0-6— wherein 0 to 6 nonadjacent methylene units are replaced with O, NR12, S or a combination thereof; and R11 and R12 are as defined in claim 1.
- 32. A compound of claim 29, wherein Z is —O—(CH2)2-3—O—(CH2)1-2—, —O—(CH2)3-4—O—, O—(CH2)1-2-, —(CH2)—O—(CH2)2-3—O—(CH2)0-1-, —C(O)—NR11—(CH2)2—, —C(O)—NR11—(CH2)2—O—, or —O—(CH2)3—S—(CH2)1—; and
R11 is as defined in claim 1.
- 33. A compound of claim 1, wherein when W is absent, Z is hydroxyl, C1-C12 alkyl wherein 1 to 6 nonadjacent methylene units are replaced with O, or —(CH2)0-6—C(O)—NR16—(CH2)0-5—CH3 wherein 0 to 6 nonadjacent methylene units are replaced with O; and
R16 is as defined in claim 1.
- 34. A compound of claim 1, wherein Z is —O—(CH2)3—O—(CH2)—.
- 35. A compound of claim 1, wherein W is unsubstituted or substituted phenyl.
- 36. A compound of claim 1, wherein W is 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2-chloro-4-fluorophenyl, 4-fluoro-2-trifluoromethylphenyl, 2-(2-acetoxy-ethyl)-phenyl, 3-(2-acetoxy-ethyl)-phenyl, 4-(2-acetoxy-ethyl)-phenyl, N,N-dimethyl-benzamide-4-yl, or 4-acetylaminophenyl.
- 37. A compound of claim 1, wherein W is 2-methoxyphenyl.
- 38. A compound of claim 1, wherein W is unsubstituted or substituted heteroaryl
- 39. A compound of claim 38, wherein W is unsubstituted indolyl.
- 40. A compound of claim 39, wherein W is 1H-Indol-3-yl.
- 41. A compound of claim 1, wherein Z is —O—(CH2)3—O—CH2—, and W is 2-methoxyphenyl.
- 42. A compound of claim 1, wherein Q is —NH—CH2— or —NR8—CH2—; T is unsubstituted naphthyl, unsubstituted 4-trifluoromethylphenyl, unsubstituted 1,2,3,4-tetrahydroquinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-5-indolyl, 1-(2-acetylaminoethyl)-5-indolyl, 1-(3-methoxypropyl)-5-indolyl, 1-acetamidyl-5-indolyl, 1-(2-acetoxyethyl)-5-indolyl, 1-(3-methoxy-3-oxopropyl)-5-indolyl, 1-(2-methoxy-2-oxoethyl)-5-indolyl, 1-(2-ethoxy-2-oxoethyl)-6-indolyl, 1-(2-acetylaminoethyl)-6-indolyl, 1-(3-methoxypropyl)-6-indolyl, 1-acetamidyl-6-indolyl, 1-(2-acetoxyethyl)-6-indolyl, 1-(3-methoxy-3-oxopropyl)-6-indolyl, 1-(2-methoxy-2-oxoethyl)-6-indolyl, 4-(2-ethoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(3-methoxypropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-acetylaminoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-acetamidyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-acetoxyethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(3-methoxy-3-oxopropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-methoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 1-(3-hydroxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-hydroxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-acetyl-3,4-dihydro-2H-quinolin-6-yl, 1-acetyl-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(4-thiazolylmethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-6-yl, 1-acetamidyl-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetylaminoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxy-3-oxopropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetylaminoethyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxy-3-oxopropyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(2-ethoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-6-yl, 2-oxo-1,2,3,4-tetrahydro-2H-quinolin-7-yl, 2-oxo-1,2,3,4-tetrahydro-2H-quinolin-6-yl, 1-(2-acetylaminoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxy-3-oxopropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-methoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetylaminoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxy-3-oxopropyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-methoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetoxyethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetoxyethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetoxyethyl)-3,4-dihydro-2H-quinolin-6-yl or 1-(2-acetoxyethyl)-3,4-dihydro-2H-quinolin-7-yl; and R8 is C1-C3 alkyl.
- 43. A compound of claim 1 having the formula II or III
- 44. A compound of Formula IV or V
- 45. A compound of claim 44, wherein T is substituted aryl.
- 46. A compound of claim 45, wherein T is substituted phenyl, naphthyl, biphenyl, 1,2,3,4-tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydro-naphthyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2,3,4-tetrahydroindolyl, 2,3-dihydroindolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, or 3,4-dihydro-2H-benzo[1,4]oxazinyl.
- 47. A compound of claim 44, wherein T is naphthyl, 1,2,3,4-tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydronaphthyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinoxalinyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydroindolyl, or 1,2,3,4-tetrahydroindolyl substituted from 1 to 7 times with, C1-C6 alkyl, halo, hydroxy, oxo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16—(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 48. A compound of claim 44, wherein T is unsubstituted naphthyl, unsubstituted 4-trifluoromethylphenyl, unsubstituted 1,2,3,4-tetrahydroquinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-5-indolyl, 1-(2-acetylaminoethyl)-5-indolyl, 1-(3-methoxypropyl)-5-indolyl, 1-acetamidyl-5-indolyl, 1-(2-acetoxyethyl)-5-indolyl, 1-(3-methoxy-3-oxopropyl)-5-indolyl, 1-(2-methoxy-2-oxoethyl)-5-indolyl, 1-(2-ethoxy-2-oxoethyl)-6-indolyl, 1-(2-acetylaminoethyl)-6-indolyl, 1-(3-methoxypropyl)-6-indolyl, 1-acetamidyl-6-indolyl, 1-(2-acetoxyethyl)-6-indolyl, 1-(3-methoxy-3-oxopropyl)-6-indolyl, 1-(2-methoxy-2-oxoethyl)-6-indolyl, 4-(2-ethoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(3-methoxypropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-acetylaminoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-acetamidyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-acetoxyethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(3-methoxy-3-oxopropyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 4-(2-methoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 1-(3-hydroxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-hydroxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-acetyl-3,4-dihydro-2H-quinolin-6-yl, 1-acetyl-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(4-thiazolylmethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-acetamidyl-3,4-dihydro-2H-quinolin-6-yl, 1-acetamidyl-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetylaminoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxy-3-oxopropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetylaminoethyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxy-3-oxopropyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-6-yl, 1-(2-ethoxy-2-oxoethyl)-3,4-dihydro-2H-quinolin-6-yl, 2-oxo-1,2,3,4-tetrahydro-2H-quinolin-7-yl, 2-oxo-1,2,3,4-tetrahydro-2H-quinolin-6-yl, 1-(2-acetylaminoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxy-3-oxopropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(3-methoxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-methoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetylaminoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxy-3-oxopropyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(3-methoxypropyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-methoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetoxyethyl)-2-oxo-3,4-dihydro-2H-quinolin-6-yl, 1-(2-acetoxyethyl)-2-oxo-3,4-dihydro-2H-quinolin-7-yl, 1-(2-acetoxyethyl)-3,4-dihydro-2H-quinolin-6-yl or 1-(2-acetoxyethyl)-3,4-dihydro-2H-quinolin-7-yl.
- 49. A compound of claim 44, wherein T is quinolinyl, isoquinolinyl or quinoxalinyl substituted from 1 to 7 times with C1-C6 alkyl, halo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16-(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 50. A compound of claim 44, wherein T is pyridyl, indolyl, pyrimidinyl, or pyrazinyl, substituted from 1 to 5 times with C1-C6 alkyl, halo, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16—(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16—S(O)2—(C1-C6 alkyl)0-1-, or HO—(C1C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl or a combination thereof.
- 51. A compound of claim 44, wherein T is N-substituted 1,2,3,4-tetrahydroquinolin-7-yl, N-substituted 1,2,3,4-tetrahydroquinolin-6-yl, N-substituted 2-oxo-1,2,3,4-tetrahydroquinolin-7-yl, N-substituted 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl, N-substituted 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, N-substituted 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl, N-substituted 2-oxo-4a,8a-dihydro-2H-chromen-7-yl, N-substituted 2,3-dihydroindol-6-yl, N-substituted 2-oxo-2,3-dihydroindol-6-yl, N-substituted 2,3-dihydroindol-5-yl, N-substituted 2-oxo-2,3-dihydroindol-5-yl, N-substituted 6-indolyl or N-substituted 5-indolyl.
- 52. A compound of claim 51, wherein the N-substituent is C1-C6 alkyl, C1-C6 alkyl wherein 1 to 3 nonadjacent carbons are replaced with O, NR16, S or a combination thereof, (C1-C6 alkyl)-C(O)—O—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-O—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—N(R16)—, (C1-C6 alkyl)-NR16—C(O)—(C1-C6 alkyl)0-1-, trifluoromethyl, (C1-C6 alkyl)-C(O)—NR16-(C1-C6 alkyl)0-1-, HO—C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-C(O)—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-S(O)2—NR16—(C1-C6 alkyl)0-1-, (C1-C6 alkyl)-NR16-S(O)2—(C1-C6 alkyl)-, or HO—(C1-C6 alkyl), wherein each R16 is independently H or C1-C6 alkyl.
- 53. A compound of claim 44, wherein W is unsubstituted or substituted phenyl.
- 54. A compound of claim 53, wherein W is 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2-chloro-4-fluorophenyl, 4-fluoro-2-trifluoromethylphenyl, 2-(2-acetoxy-ethyl)-phenyl, 3-(2-acetoxy-ethyl)-phenyl, 4-(2-acetoxy-ethyl)-phenyl, N,N-dimethyl-benzamide-4-yl, or 4-acetylaminophenyl.
- 55. A compound of claim 44, wherein W is 2-methoxyphenyl.
- 56. A compound of claim 44, wherein T is unsubstituted naphthyl, unsubstituted 4-trifluoromethylphenyl, unsubstituted 1,2,3,4-tetrahydroquinolin-7-yl, 1-(3-hydroxypropyl)-3,4-dihydro-2H-quinolin-7-yl, or 1-(2-acetoxy-ethyl)-3,4-dihydro-2H-quinolin-7-yl and W is 2-methoxyphenyl.
- 57. The compound
(4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-naphthalen-2-ylmethyl-amine, (4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-(6-methoxy-naphthalen-2-ylmethyl)-amine, (4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-quinolin-7-ylmethyl-amine, (4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-(1,2,3,4-tetrahydro-quinolin-7-ylmethyl)-amine, (4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-methyl-naphthalen-2-ylmethyl-amine, 6-[(4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-naphthalen-2-ol, benzofuran-5-ylmethyl-(4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-amine, (1H-indol-5-ylmethyl)-(4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-amine; 6-[(4-[3-(2-methoxy-benzyloxy)-propoxyl]-phenyl}-piperidin-3-ylamino)-methyl]-naphthalene-1-carboxylic acid methyl ester; 6-[(4-[4-(2-methoxy-benzyloxy)-propoxyl]-phenyl}-piperidin-3-ylamino)-methyl]-naphthalene-1-carboxylic acid; naphthalene-1-carboxylic acid (4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-amide; 6-[(4-{4-[3-(2-methoxy-benyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-naphthalene-2-carboxylic acid methyl ester; (4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-quinolin-7-ylmethyl-amine; 6-[(4-{4-[3-(2-fluoro-benyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-naphthalene-2-carboxylic acid methyl ester; 6-[(4-{4-[3-(2-fluoro-benyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-naphthalene-2-carboxylic acid; 6-[(4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-pyridine-2-carboxylic acid methyl ester; naphthalene-2-sulfonic acid (4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-amide; (4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-(4-fluoro-3-trifluoromethyl-benzyl)-amine; {3-[(4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-phenoxy}-acetic acid methyl ester; 1-(2-{3-[(4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-phenoxy}-ethyl)-pyrrolidine-2,5-dione; 1-(2-{3-[(4-{4-[3-(2-fluoro-benzyloxy)-propoxy]-phenyl}-piperidin-3-ylamino)-methyl]-phenoxy}-ethyl)-pyrrolidine-2-one; 3-[(1-dimethylcarbamoylmethyl-1, 2, 3, 4-tetrahydro-quinoline-7-carbonyl)-amino]-4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester; or [1-(2-dimethylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethyl]-(4-{4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl}-piperidin-3-yl)-amine.
- 58. A pharmaceutical composition comprising a compound of any of claims 1-57, admixed with a pharmaceutically acceptable carrier, diluent, or excipient.
- 59. A method of inhibiting renin in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 60. A method of treating or preventing hypertension in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 61. A method of treating or preventing congestive heart failure in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 62. A method of treating or preventing stroke in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 63. A method of treating or preventing myocardial infarction in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 64. A method of treating or preventing glaucoma in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 65. A method of providing end organ protection in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 66. A method of treating or preventing hyperaldosteronism in a mammal comprising administering to the mammal in need thereof an effective amount of a compound of any of claims 1-57.
- 67. A process for preparing a compound of claim 1 comprising the steps of:
a) alkylation of piperidine 1 to afford the intermediate 2 wherein R20 along with the oxygen to which it is attached, is equivalent to -Z-W as defined in claim 1;61b) oxidation of 2 to afford the piperidinone intermediate 3; 62c) contacting 3 with a suitable amine to afford the intermediate 4, wherein R21, along with the nitrogen to which it is attached is equivalent to -Q-T as defined in claim 1;63d) deprotection of 4 to afford 564
Parent Case Info
[0001] The present application claims priority under 35 USC section 119(e) to U.S. Provisional Application Serial No. 60/461,962, filed Apr. 10, 2003 and U.S. Provisional Application Serial No. 60/542,279, filed Feb. 9, 2004.
Provisional Applications (2)
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Number |
Date |
Country |
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60461962 |
Apr 2003 |
US |
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60542279 |
Feb 2004 |
US |