Claims
- 1. A compound of the formula: ##STR8## and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo; X is CO, S(O).sub.2 or S(O)--(CH.sub.2)n wherein S atom is directly attached to the phenyl and n is 0, 1 or 2; and R.sup.1 is 8-azabicyclo[3.2.1]octyl, quinuclidinyl, bicyclo[3.3.0]octyl, C.sub.3-10 cycloalkyl, 2,3,5,6-tetrahydro-4H-thiopyranyl or C.sub.3-6 cycloalkyl-C.sub.1-4 alkyl, optionally substituted with C.sub.1-4 alkyl, hydroxy, dioxolanespiro or oxo.
- 2. A compound according to claim 1, wherein A.sup.1 and A.sup.2 are chloro.
- 3. A compound according to claim 2, wherein R.sup.1 is 8-methyl-8-azabicyclo[3.2.1]oct-3-yl, quinuclidin-3-yl, 3-hydroxy-bicyclo[3.3.0]oct-7-yl, [1-(hydroxy) cyclopentyl]ethyl or 3-oxo-bicyclo[3,3,0]oct-7-yl.
- 4. A compound according to claim 1, being one of the following:
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-piperazinyl]carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-piperazinyl]carbonylmethyl-6-(2-oxo-2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-(2-oxo-2-phenylethyl)-2-[4-(3-quinuclidinyl)-1-piperazinyl]carbonylmethyl-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-(2-oxo-2-phenylethyl)-2-[4-(3-hydroxy-bicyclo[3.3.0]oct-7-yl)piperazin-1-yl]carbonylmethyl-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-2-{2-[1-(hydroxy) cyclopentyl]ethylpiperazinyl} carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate;
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3,2,1]octan-3-yl)-1-piperazinyl]carbonylmethyl-6-(phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(3-hydroxy-bicyclo[3,3,0]oct-7-yl)-1-piperazinyl]carbonylmethyl-6-(phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate monohydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(3-oxo-bicyclo[3,3,0]oct-7-yl)piperazinyl]-carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate, monocitric acid;
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(cis-1,5-dimethyl-3-oxo-bicyclo[3,3,0]oct-7-yl)-piperazinyl]carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate, monohydrochloride; and
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(5-oxo-cyclooctyl)-piperazinyl]carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate, monohydrochloride.
- 5. A compound according to claim 4, being one of the following:
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-piperazinyl]carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-piperazinyl]carbonylmethyl-6-(2-oxo-2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride;
- dimethyl 4-(2,6-dichlorophenyl)-(2-oxo-2-phenylethyl)-2-[4-(3-quinuclidinyl)-1-piperazinyl]carbonylmethyl-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride; and
- dimethyl 4-(2,6-dichlorophenyl)-(2-oxo-2-phenylethyl)-2-[4-(3-hydroxy-bicyclo[3.3.0]oct-7-yl)piperazin-1-yl]carbonylmethyl-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride.
- 6. A compound according to claim 5,
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-piperazinyl]carbonylmethyl-6-phenylsulfinylmethyl-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride; or
- dimethyl 4-(2,6-dichlorophenyl)-2-[4-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-piperazinyl]carbonylmethyl-6-(2-oxo-2-phenylethyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride.
- 7. A pharmaceutical composition for the treatment of inflammation, cardiovascular disease, pain, common cold, allergies, asthma, pancreatitis, burns, virus infection, head injury, multiple trauma, which comprises a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 8. A method for the treatment of disease conditions caused by bradykinin, in a mammalian subject, which comprises administering to said subject a therapeutically effective amount of a compound according to claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/IB96/00132 |
Feb 1996 |
WOX |
|
Parent Case Info
This application is the U.S. national stage Section 371 of International application No. PCT/IB96/00058, filed Jan. 27, 1997, which claims the priority of International application No. PCT/IB96/00132, filed Feb. 19, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/IB97/00058 |
1/27/1997 |
|
|
2/1/1999 |
2/1/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/30048 |
8/21/1997 |
|
|
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5859011 |
Ito et al. |
Jan 1999 |
|
5861402 |
Ikeda |
Jan 1999 |
|