Claims for Patent: 5,856,346

Summary for Patent: 5,856,346

Title:	Short-acting dihydropyridines
Abstract:	Compounds of the general formula ##STR1## wherein R1 and R2 are independently selected from the group consisting of hydrogen, chloro, bromo, nitro, cyano, trifluoromethyl, and R3 and R4 are independently selected from straight or branched lower (1-5 carbon atoms) alkyl groups, and including all optical isomers, provided that when R3 is methyl and R4 is tert.-butyl, then R1 /R2 are not hydrogen/hydrogen, hydrogen/2'-trifluormethyl, 2'-chloro/3'-chloro, and when R3 is methyl and R1 /R2 is hydrogen/3'-nitro, then R4 are not methyl, ethyl, propyl, iso-propyl, tert.-butyl, processes for their preparation, pharmaceutical preparations containing them and the use of the compounds in lowering the blood pressure.
Inventor(s):	Kjell Hjalmar Andersson, Margareta Nordlander, Rolf Christer Westerlund
Assignee:	Chiesi Farmaceutici SpA
Application Number:	US08/356,224
Patent Claims:	1. A compound of the formula ##STR12## wherein R1 and R2 are independently selected from the group consisting of hydrogen, chloro, bromo, nitro, cyano and trifluoromethyl, and R3 and R4 are independently selected from the group consisting of straight and branched C1-5 alkyl groups and including all optical isomers, provided that when R3 is methyl and R4 is tert-butyl, then R1 /R2 are not hydrogen/hydrogen, hydrogen/ 2'-trifluoromethyl, 2'-chloro/3'-chloro, and when R3 is methyl and R2 /R1 is hydrogen/3'-nitro, then R4 is not methyl, ethyl, propyl, iso-propyl or tert-butyl or a pharmaceutically acceptable salt thereof. 2. A compound according to claim 1, selected from1) Butyroxymethyl methyl 4-(2'3'-dichlorophenyl)2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate 2)(4S)-Butyroxymethyl methyl 4-(2',3'-dichlorophenyl)2,6-dimethyl-1,4-dihydropyridi ne-3 ,5-dicarboxylate 3) (4R)-Butyroxymethyl methyl 4-(2',3'-dichlorophenyl)2,6-dimethyl-1,4-dihydropyridi ne-3 ,5-dicarboxylate 4) iso-Butyroxymathyl methyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate. 3. A process for the preparation of a compound of the formula I as defined in claim 1, whereina) alkylation of a compound of the formula 11 ##STR13## with a compound of the formula R.sub.4 COOCH.sub.2 X in which formulas R1 -R4 are defined in claim 1 and X is a standard leaving group, or b) condensation of a compound of the formula III ##STR14## with an aminocrotonate of the formula IV ##STR15## in which formulas R1 -R4 are as defined in claim 1, or c) condensation of a compound of the formula V ##STR16## with an aminocrotonate of the formula VI ##STR17## in which formulas R1 -R4 are defined in claim 1 or d) reaction of a benzaldehyde of the formula VIII ##STR18## with a acetoacetate of the formula VII ##STR19## and an aminocrotonate of the formula VI ##STR20## in which formulas R1 -R4 are as defined in claim 1, or e) reaction of a benzaldehyde of the formula VIII ##STR21## with an acetoacetate of the formula IX ##STR22## and an aminocrotonate of the formula IV ##STR23## in which formulas R1 -R4 are as defined in claim 1, or f) reaction of a benzylidene compound of the general formula III ##STR24## with an acetoacetate of the general formula VII ##STR25## in the presence of ammonia, in which formulas R1 -R4 are as defined in claim 1, or g) reaction of a benzylidene compound of the general formula V ##STR26## with an acetoacetate of the formula IX ##STR27## in the presence of ammonia, in which formulas R1 -R4 are as defined in claim 1, or h) reaction of acetoacetates of the general formulas VII and IX ##STR28## ##STR29## with a benzaldehyde of the general formula VIII ##STR30## in the presence of ammonia, in which formulas R1 -R4 are as defined in claim 1, alternatively wherein the compound obtained by any of the processes a)-h) is converted to an optical isomer thereof by known methods. 4. A process according to claim 3, wherein a compound according to claim 2 is prepared. 5. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or 2. 6. A pharmaceutical composition according to claim 5 in dosage unit form. 7. A pharmaceutical composition according claim 5 comprising a compound according to claim 1 or 2 in association with a pharmaceutically acceptable carrier. 8. A method for lowering the blood pressure in a host comprising administering to a host in need of such treatment an effective amount of a compound according to claim 1 or 2.