Novel dihydropyridines

Claim 2

A compound of the formula wherein R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, ND 2 , CN, CF 3 , Cl and Br; A is a straight or branched alkylene group with 2-5 carbon atomms; R2 is wherein B is a straight or branched alkylene group with 2-5 carbon atoms and R 3 and R are the same or different and each represents a straight or branched alkyl group with 1-5 carbon atoms, an alkylaryl group or both together are part of a 5-7 membered heterocyclic ring; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl-group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower alkyl group, or a physiologically acceptable salt or optical isomer thereof.

Claim 3

A compound according to claim 1; 1) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-L2-(2-N,N-dimethylaminoethylthio)-ethyl]-5-methyl ester 2) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-12-(2-N,N-dimethylaminoethylthio)-ethyl]-5-(2-methylethyl)ester 3) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-[2-(2-N,N-dimethylaminoethylthio)-ethyl]-5-ethyl ester 4) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-(2-(2-N,N-dimethylaminoetylthio- ethyl]-5-(2-methoxyethyl) ester 5) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-[2-(2-N,N-diethylaminoethylthio)-ethylJ-5-methyl ester 6) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-[2-(2-morpholinoethylthio)-ethyl]--5-methyl ester 7) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-[2-(N-isopropyl-N-benzylaminoethyl- thio]ethyl]-5-methyl ester 8) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-[2-(3-N,N-dimethylaminopropylthio)-ethyl]-5-methyl ester 9 ) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-(2-(2-N-isopropyl-N-benzylethyl- thio)ethyl]-5-(2-methoxyethyl) ester 1 0 ) 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine--3,5-dicarboxylic acid-3-[2-(2-morpholinoethylthio)-ethyl]--5-(2-metnoxyethyl) ester 11) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5--dicarboxylic acid-3-[2-(2-N,N-dimethylaminoethylthio)ethyl]--5-methyl ester 12) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-[2-(N,N-dimethylaminoethylthio)ethyl]--5-methyl ester 13) 2,6-dimethyl-4-(3-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylic aeid-3-[2-(2-N,N-dimethylaminaethylthio) ethyl]-5-methyl ester

Claim 4

A compound according to any of claims 1-2 in the form of an optical isomer thereof.

Claim 5

A compound according to any of claims 1-3 in the form of a physiologically acceptable salt thereof.

Claim 6

A process for preparing a compound of the formula wherein R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, ND 2 , CN, CF 3 , C1 and Br; A is a straight or branched alkylene group with 2-5 carbon atomms; R 2 is wherein B is a straight or branched alkylene group with 2-5 carbon atoms and R 3 and R 6 are the same or different and each represents a straight or branched alkyl group with 1-5 carbon atoms, an alkylaryl group or both together are part of a 5-7 membered heterocyclic ring; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower.alkyl group, or a physiologically acceptable salt or optical isomer thereof. characterized in that a 1 ) a compound of the formula wherein R 1 , R 4 and R 5 have the meanings given above, is reacted with a compound of the formula wherein A and R 2 and R 5 have the meanings given above, to the formation of a compound of the formula I; or a 2 ) a compound of the formula wherein R 1 , R2, R 5 and A have the meanings given above, is reacted with a compound of the formula wherein R 4 and R5 have the meaning given above, to the formation of a compound of the formula I; or b 1 ) a compound of the formula wherein R 1 has the meaning given above, is reacted with compounds of the formulas and wherein R 2 , R 4 , R 5 and A have the meanings given above, to the formation of a compound of the formula I; or b 2 ) a compound of formula IV above, wherein R 1 has the meaning given above, is reacted with compounds of the formulas and wherein R 2 , R 4 , R 5 and A have the meanings given above, to the formation of a compound of the formula I; or c 1 ) a compound of formula II a above, wherein R 1 , Rand R 5 have the meanings given above, is reacted with a compound of the formula wherein R 2 , R and A have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I; or c ) a compound of formula II b above, wherein R 1 , R 2 , R and A have tne meanings given above, is reacted with a compound of the formula wherein R 4 and R 5 have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I, or d) a compound of formula IV above, wherein R has the meaning given above, is reacted with the compounds of the formulas V a and V b, wherein R 2 , R 4 , R 5 and A have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I, whereafter, if desired, the compound obtained by any of methods a l ) - d ) is converted to a physiologically acceptable salt thereof and/or converted to a substantially pure stereoisomer thereof.

Claim 7

A process for preparing a compound of the formula wherein R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, ND 2 , CN, CF 3 , C1 and Br; A is a straight or branched alkylene group with 2-5 carbon atomms; R 2 is wherein B is a straight or branched alkylene group with 2-5 carbon atoms and R 3 and R 6 are the same or different and each represents a straight or branched alkyl group with 1-5 carbon atoms, an alkylaryl group or both together are part of a 5-7 membered heterocyclic ring; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower.alkyl group, or a physiologically acceptable salt or optical isomer thereof. characterized in that a 1 ) a compound of the formula wherein R 1 , R 4 and R 5 have the meanings given above, is reacted with a compound of the formula wherein A and R 2 and R 5 have the meanings given above, to the formation of a compound of the formula I; or a 2 ) a compound of the formula wherein R 1 , R2, R 5 and A have the meanings given above, is reacted with a compound of the formula wherein R 4 and R5 have the meaning given above, to the formation of a compound of the formula I; or b 1 ) a compound of the formula wherein R 1 has the meaning given above, is reacted with compounds of the formulas and wherein R 2 , R 4 , R 5 and A have the meanings given above, to the formation of a compound of the formula I; or b 2 ) a compound of formula IV above, wherein R 1 has the meaning given above, is reacted with compounds of the formulas and wherein R 2 , R 4 , R 5 and A have the meanings given above, to the formation of a compound of the formula I; or c 1 ) a compound of formula II a above, wherein R 1 , Rand R 5 have the meanings given above, is reacted with a compound of the formula wherein R 2 , R and A have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I; or c ) a compound of formula II b above, wherein R 1 , R 2 , R and A have tne meanings given above, is reacted with a compound of the formula wherein R 4 and R 5 have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I, or d) a compound of formula IV above, wherein R has the meaning given above, is reacted with the compounds of the formulas V a and V b, wherein R 2 , R 4 , R 5 and A have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I, whereafter, if desired, the compound obtained by any of methods a l ) - d ) is converted to a physiologically acceptable salt thereof and/or converted to a substantially pure stereoisomer thereof.

Claim 8

A process according to claim 5 characterized in that a compound according to any of claims 1-4 is prepared.

Claim 9

A pharmaceutical preparation comprising as active ingredient a compound according to any of claims 1-4 or a physiologically acceptable salt or an optical isomer thereof.

Claim 10

A pharmaceutical preparation according to claim 7 in dosage unit form.

Claim 11

A pharmaceutical preparation according to claims 7-8 comprising the active ingredient in association with a pharmaceutically acceptable carrier.

Claim 12

The use of a compound according to any of claims 1-4 or a physiologically acceptable salt thereof for the preparation of a pharmaceutical preparation comprising as an active ingredient an amount of said compound.

Claim 13

Use of a compound according to any of claims 1-4 as a drug for the treatment of cardiovascular diseases and other disorders where smooth muscle relaxation is therapeutically important, particularly hypertension.

Claim 14

The use of a compound according to any of claims 1-2 or a salt or an optical isomer thereof as an intermediate for the preparation of therapeutically active dihydropyridines.

Claim 15

A process for preparing a compound of the formula wherein A is a straight or branched alkylene group with 2-5 carbon atoms and R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, ND 2 , CN, CF 3 , Cl or Br; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower alkyl group; or a physiologically acceptable salt or optical isomer thereof, characterized in that a compound of the formula wherein R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, N0 2 , CN, CF 3 , Cl and Br; A is a straight or branched alkylene group with 2 - 5 carbon atoms; R is wherein B is a straight or branched alkylene group with 2-5 carbon atoms and R 3 and R 6 are the same or different and each represents a straight or branched alkyl group with 1-5 carbon atoms, an alkylaryl group or both together are part of a 5-7 membered heterocyclic ring; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower alkyl group, or a physiologically acceptable salt or optical isomer thereof, is treated in a solvent with a Raney catalyst.

Claim 16

A process for preparing a compound of the formula wherein A is a straight or branched alkylene group with 2-5 carbon atoms and R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, ND 2 , CN, CF 3 , Cl or Br; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower alkyl group; or a physiologically acceptable salt or optical isomer thereof, characterized in that a compound of the formula wherein R 1 is one or two (the same or different) substituents on the phenyl ring selected from the group consisting of lower alkyl, N0 2 , CN, CF 3 , Cl and Br; A is a straight or branched alkylene group with 2 - 5 carbon atoms; R is wherein B is a straight or branched alkylene group with 2-5 carbon atoms and R 3 and R 6 are the same or different and each represents a straight or branched alkyl group with 1-5 carbon atoms, an alkylaryl group or both together are part of a 5-7 membered heterocyclic ring; R 4 is a straight or branched alkyl group with 1-5 carbon atoms or a straight or branched alkyl group with 1-5 carbon atoms in which alkyl group the carbon chain is interrupted by an oxygen atom; R 5 is a lower alkyl group, or a physiologically acceptable salt or optical isomer thereof, is treated in a solvent with a Raney catalyst.