6-Substituted 4-(2',3'-dichlorophenyl)-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid diesters having hypotensive properties as well as process for their preparation and pharmaceutical preparations containing same

Claim 2

A compound of the formula I wherein R 1 is selected from the group consisting of -CH 3 , -CH 2 CH 2 OCH 3 and -CH(CH 3 )CH 2 OCH 3 , R 2 is selected from the group consisting of -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , whereby when R 1 is -CH 3 , R 2 is -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , when R 1 is--CH 2 CH 2 OCH 3 , R 2 is -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , and when R 1 is -CH(CH 3 )CH 2 OCH 3 R 2 is -CH(CH 3 )CH 2 OCH 3 , and R 3 is selected from the group consisting of alkyl with 2 to 3 carbon atoms, alkoxyalkyl with 2 to 3 carbon atoms, and alkoxyalkoxyalkyl with 3 to 5 carbon atoms.

Claim 3

A compound according to claim 1, wherein 1) 2-isopropyl-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid-3-ethylester-5-methylester 2) 2-methoxymethyl-4-(2,3-dichlorophenyl)-6-methyl-1,4--dihydropyridine-3,5-dicarboxylic acid-3-ethylester-5--methylester 3) 2-(2-methoxyethyl)-4-(2,3-dichlorophenyl)-6-methyl-1,4--dihydropyridine-3,5-dicarboxylic acid-3-ethylester-5--methylester 4) 2-ethyl-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid-3-ethylester-5-methylester 5) 2-(2-methoxyethoxy)methyl-4-(2,3-dichlorophenyl)-6--methyl-1,4-dihydropyridine-3,5-dicarboxylic acid-3--ethyl-5-methylester 6) 2-methoxymethyl-4-(2,3-dichlorophenyl)-6-methyl-1,4--dihydropyridine-3,5-dicarboxylic acid-3-(2-methoxy)--ethylester-5-methylester is selected.

Claim 4

A process for preparing compounds of the formula I wherein R is selected from the group consisting of -CH3, -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , R 2 is selected from the group consisting of -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , whereby when R 1 is -CH3, R 2 is -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , when R 1 is -CH 2 CH 2 OCH 3 , R 2 is -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , and when R 1 is -CH(CH 3 )CH 2 OCH 3 , R 2 is -CH(CH 3 )CH 2 OCH 3 , and R 3 is selected from the group consisting of alkyl with 2 to 3 carbon atoms, alkoxyalkyl with 2 to 3 carbon atoms, and alkoxyalkoxyalkyl with 3 to 5 carbon atoms characterized in that a 1 ) a compound of formula IIa wherein R has the meanings given above is reacted with a compound of formula IIIa wherein R 2 and R 3 have the meanings given above to the formation of a compound of the formula I; a ) a compound of formula IIb wherein R 2 and R 3 have the meanings given above is reacted with a compound of formula IIIb wherein R 1 has the meaning given above, to the formation of a compound of formula I; b 1 ) a compound of formula IV is reacted with the compounds of formulas Va and IIIa wherein R 1 , R 2 , and R 3 have the meanings given above to the formation of a compound of formula I, b 2 ) a compound of formula IV above, is reacted with the compounds of formula Vb and IIIb wherein R 1 , R 2 , and R 3 have the meanings given above, to the formation of a compound of formula I; c l ) a compound of formula IIa above, wherein R has. the meanings given above is reacted with a compound of the formula VIa wherein R 2 and R 3 have the meanings given above in the presence of ammonia, to the formation of a compound of the formula I, c ) a compound of formula IIb wherein R 2 and R 3 have the meanings given above is reacted with a compound of formula VIb wherein R 1 has the meaning given above, in the presence of ammonia, to the formation of a compound of the formula I; d) a compound of formula IV above, is reacted with the compounds of the formulas Va and Vb above, wherein R 1 R 2 and R 3 have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I, or e) a compound of formula VII wherein R 1 and R 2 have the meanings given above and alkyl is a lower alkyl with 1 to 2 carbon atoms, is reacted with a compound Hal-alkyl or Hal-alkyl -0-alkyl wherein alkyl and alkyl" denote a lower alkyl having 1 to 2 carbon atoms, and Hal denotes halogen to the formation of a compound of the formula I.

Claim 5

A process for preparing compounds of the formula I wherein R is selected from the group consisting of -CH3, -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , R 2 is selected from the group consisting of -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , whereby when R 1 is -CH3, R 2 is -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , when R 1 is -CH 2 CH 2 OCH 3 , R 2 is -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , and when R 1 is -CH(CH 3 )CH 2 OCH 3 , R 2 is -CH(CH 3 )CH 2 OCH 3 , and R 3 is selected from the group consisting of alkyl with 2 to 3 carbon atoms, alkoxyalkyl with 2 to 3 carbon atoms, and alkoxyalkoxyalkyl with 3 to 5 carbon atoms characterized in that a 1 ) a compound of formula IIa wherein R has the meanings given above is reacted with a compound of formula IIIa wherein R 2 and R 3 have the meanings given above to the formation of a compound of the formula I; a ) a compound of formula IIb wherein R 2 and R 3 have the meanings given above is reacted with a compound of formula IIIb wherein R 1 has the meaning given above, to the formation of a compound of formula I; b 1 ) a compound of formula IV is reacted with the compounds of formulas Va and IIIa wherein R 1 , R 2 , and R 3 have the meanings given above to the formation of a compound of formula I, b 2 ) a compound of formula IV above, is reacted with the compounds of formula Vb and IIIb wherein R 1 , R 2 , and R 3 have the meanings given above, to the formation of a compound of formula I; c l ) a compound of formula IIa above, wherein R has. the meanings given above is reacted with a compound of the formula VIa wherein R 2 and R 3 have the meanings given above in the presence of ammonia, to the formation of a compound of the formula I, c ) a compound of formula IIb wherein R 2 and R 3 have the meanings given above is reacted with a compound of formula VIb wherein R 1 has the meaning given above, in the presence of ammonia, to the formation of a compound of the formula I; d) a compound of formula IV above, is reacted with the compounds of the formulas Va and Vb above, wherein R 1 R 2 and R 3 have the meanings given above, in the presence of ammonia, to the formation of a compound of the formula I, or e) a compound of formula VII wherein R 1 and R 2 have the meanings given above and alkyl is a lower alkyl with 1 to 2 carbon atoms, is reacted with a compound Hal-alkyl or Hal-alkyl -0-alkyl wherein alkyl and alkyl" denote a lower alkyl having 1 to 2 carbon atoms, and Hal denotes halogen to the formation of a compound of the formula I.

Claim 6

Pharmaceutical preparation which comprises as an active ingredient a therapeutically effective dose of at least one antihypertensive compound having vascular smooth muscle relaxing properties which compound has the formula I wherein R 1 is selected from the group consisting of -CH 3 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , R 2 is selected from the group consisting of -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , whereby when R 1 is -CH 3 , R 2 is -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , when R 1 is

Claim 7

Pharmaceutical preparation which comprises as an active ingredient a therapeutically effective dose of at least one antihypertensive compound having vascular smooth muscle relaxing properties which compound has the formula I wherein R 1 is selected from the group consisting of -CH 3 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , R 2 is selected from the group consisting of -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , and -CH(CH 3 )CH 2 OCH 3 , whereby when R 1 is -CH 3 , R 2 is -CH 3 , -C 2 H 5 , -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , when R 1 is

Claim 8

-CH 2 CH 2 OCH 3 , R 2 is -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , and when R 1 is -CH(CH 3 )CH 2 OCH 3 , R 2 is -CH(CH 3 )CH 2 OCH 3 , and R 3 is selected from the group consisting of alkyl with 2 to 3 carbon atoms, alkoxyalkyl with 2 to 3 carbon atoms, and alkoxyalkoxyalkyl with 3 to 5 carbon atoms in association with a pharmaceutically acceptable carrier.

Claim 9

-CH 2 CH 2 OCH 3 , R 2 is -CH 2 CH 2 OCH 3 , or -CH(CH 3 )CH 2 OCH 3 , and when R 1 is -CH(CH 3 )CH 2 OCH 3 , R 2 is -CH(CH 3 )CH 2 OCH 3 , and R 3 is selected from the group consisting of alkyl with 2 to 3 carbon atoms, alkoxyalkyl with 2 to 3 carbon atoms, and alkoxyalkoxyalkyl with 3 to 5 carbon atoms in association with a pharmaceutically acceptable carrier.

Claim 10

A pharmaceutical preparation according to claim 4, wherein the substituted 2-substituted-6-methyl-4-phenyl--l,4-dihydropyridine-3,5-dicarboxylic acid-diester compound comprises 0.1 to 99% by weight of the preparation.