Claims
- 1. A 1,4-dihydropyridine derivative of the formula I: ##STR12## is provided in which: A is an azole moiety selected from the group consisting of 3-methyl-5-isoxazolyl, 3,5-dimethyl-1-pyrazolyl and 4-methyl-2-thiazolyl;
- R is a C.sub.1 -C.sub.4 alkyl group;
- X is --CH.sub.2 --, --S--, --SO-- or --SO.sub.2 --;
- n is 5, 6, 7 or 8; and
- Ph is a phenyl group substituted once or twice by NO.sub.2,
- CF.sub.3 or Cl groups.
- 2. A 1,4-dihydropyridine derivative according to claim 1 of the formula II: ##STR13## in which: A is 3-methyl-5-isoxazolyl, 3,5-dimethyl-1-pyrazolyl, or 4-methyl-2-thiazolyl;
- X is --CH.sub.2 --, --S--, --SO-- or --SO.sub.2 --;
- n is 5, 6, 7 or 8; and
- Ph is a phenyl group substituted once or twice by NO.sub.2, CF.sub.3 or Cl groups.
- 3. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl.
- 4. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl.
- 5. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl.
- 6. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is CH.sub.2, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 7. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is CH.sub.2, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 8. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is CH.sub.2, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 9. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 10. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 11. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 12. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 13. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 14. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 15. 3-[7-(3-methyl isoxazol-5-yl)heptyl-oxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 16. 3-[7-(3-methyl isoxazol-5-yl)heptyl-oxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 17. 3-[7-(3-methylisoxazol-5-yl)heptyl-oxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine, according to claim 1.
- 18. 3-[7-(3-methylisoxazol-5-yl)heptyl-oxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine, according to claim 1.
- 19. 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(3-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 20. 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(2-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 21. 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(3-trifluoromethylphenyl)-1,4-dihydropyridine, according to claim 1.
- 22. 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(2-trifluoromethylphenyl)-1,4-dihydropyridine, according to claim 1.
- 23. 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(3-chlorophenyl)-1,4-dihydropyridine, according to claim 1.
- 24. 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(2-chlorophenyl)-1,4-dihydropyridine, according to claim 1.
- 25. 3-17-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl) -1,4-dihydropyridine, according to claim 1.
- 26. 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(2-nitropheny 1)- 1,4-dihydropyridine, according to claim 1.
- 27. 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine, according to claim 1.
- 28. 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(2-trifluoromethylphenyl)-1,4-dihydropyridine, according to claim 1.
- 29. 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-chlorophenyl)-1,4-dihydropyridine, according to claim 1.
- 30. 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(2-chlorophenyl)-1,4-dihydropyridine, according to claim 1.
- 31. 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl[-5-methoxycarbonyl-2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine, according to claim 1.
- 32. 3-[6-(4-methylthiazol-2-yl)-thiohexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 33. 3-[6-(4-methylthiazol-2-yl)-sulfoxyhexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 34. 3-[6-(4-methylthiazol-2-yl)-sulfonylhexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine, according to claim 1.
- 35. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --S--, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 36. A compound of claim 2 wherein a is 3,5-dimethyl-1-pyrazolyl, X is --S--, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 37. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --S--, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 38. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --S--, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 39. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --S--, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 40. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --S--n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 41. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --SO--, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 42. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --SO--, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 43. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --SO--, n is 6 and Ph is a phenyl group substituted once or twice by NO.sub.2.
- 44. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --SO--, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 45. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --SO--, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 46. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --SO--, n is 6 and Ph is a phenyl group substituted once by CF.sub.3.
- 47. A compound of claim 2 wherein A is 4-methyl-2-thiazolyl, X is --SO-- or --S--, n is 6 and Ph is a phenyl group substituted once or twice by a Cl group.
- 48. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --SO-- or --S, n is 6 and Ph is a phenyl group substituted once or twice by a Cl group.
- 49. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --SO-- or S, n is 6 and Ph is a phenyl group substituted once or twice by a Cl group.
- 50. A compound of claim 2 wherein A is 4-methylk-2-thiazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once or twice by a CF.sub.3 group, or a NO.sub.2 group, or a Cl group.
- 51. A compound of claim 2 wherein A is 3,5-dimethyl-1-pyrazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once or twice by a CF.sub.3 group , or a NO.sub.2 group or a Cl group.
- 52. A compound of claim 2 wherein A is 3-methyl-5-isoxazolyl, X is --SO.sub.2 --, n is 6 and Ph is a phenyl group substituted once or twice by a CF.sub.3 group, or a NO.sub.2 group or a Cl group.
- 53. A composition comprising a pharmaceutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 54. A method of treating hypertension in a patient comprising administering an amount of a compound of claim 1 to a patient which is effective to reduce blood pressure.
- 55. A method of treating hypertension in a patient comprising administering an amount of the compound 3-[7-(3-methylisoxazol-5-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine of claim 15 thereto which is effective to reduce blood pressure.
- 56. A method of treating hypertension in a patient comprising administering an amount of the compound 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2, 6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyrdine of claim 19 thereto which is effective to reduce blood pressure.
- 57. A method of treating hypertension in a patient comprising administering an amount of the compound 3[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine of claim 27 thereto which is effective to reduce blood pressure.
- 58. A method of treating hypertension in a patient comprising administering an amount of the compound 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-chlorophenyl)-1,4-dihydropyridine of claim 29 thereto which is effective to reduce blood pressure.
- 59. A method of treating inflammatory activity in a patient suffering from inflammation comprising administering a compound of claim 1 in an amount effective to reduce inflammation.
- 60. A method of treating ulcer stress activity in a patient suffering from ulcer stress comprising administering a compound of claim 1 in an amount effective to reduce ulcer stress.
- 61. A method of treating inflammatory activity which comprises administering the compound 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4(3-nitrophenyl)-1,4-dihydropyridine of claim 19 to a patient suffering from inflammation in an amount effective to reduce inflammation.
- 62. A method of treating inflammatory activity which comprises administering the compound 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine of claim 27 to a patient in an amount effective to reduce inflammation.
- 63. A method of treating ulcer stress activity in a patient which comprises administering 3-[7-(3-methylisoxazol-5-yl)heptylcarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine thereto of claim 15 in an amount effective to reduce inflammation.
- 64. A method of treating ulcer stress activity in a patient which comprises administering 3-[7-(4-methylthiazol-2-yl)heptyl-oxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-chlorophenyl)-1,4-dihydropyridine thereto of claim 29 in an amount effective to reduce inflammation.
- 65. The method of claim 54, wherein said compound is selected from the group consisting of 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine; 3-[7-(3-methylisoxazol-5-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine; 3-[6-(3,5-dimethylpyrazol-1-yl)hexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine; 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine; 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-trifluoromethylphenyl)-1,4-dihydropyridine; 3-[7-(4-methylthiazol-2yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-chlorophenyl)-1,4-dihydropyridine; 3-[7-(4-methylthiazol-2-yl)heptyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine; 3-[6-(4-methylthiazol-2-yl)-thiohexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine; 3-[6-(4-methylthiazol-2-yl)-sulfoxyhexyloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine; and 3-[6-(4-methylthiazol-2-yl-sulfonylhexloxycarbonyl]-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine.
Parent Case Info
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of my application for U.S. Letter Patent Ser. No. 07/308,923, filed Feb. 13, 1989, now abandoned.
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Continuation in Parts (1)
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308923 |
Feb 1989 |
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