Claims for Patent: 4,264,611

Summary for Patent: 4,264,611

Title:	2,6-Dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same
Abstract:	The present invention relates to new compounds having antihypertensive effect, which compounds are of the formula I, ##STR1## wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, and R.sup.2 is selected from the group consisting of --C.sub.2 H.sub.5, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, whereby R.sup.1 and R.sup.2 are not the same, R.sup.3 is selected from the group consisting of chloro, and R.sup.4 is selected from the group consisting of chloro, and methyl, a method for lowering the blood pressure in mammals including man using said compounds, and pharmaceutical preparations containing said compounds.
Inventor(s):	Berntsson; Peder B. (Molndal, SE), Carlsson; Stig A. I. (Molnlycke, SE), Gaarder; Jan O. (Goteborg, SE), Ljung; Bengt R. (Goteborg, SE)
Assignee:	Aktiebolaget Hassle (Molndal, SE)
Application Number:	06/050,083
Patent Claims:	1. A compound of the formula I ##STR13## wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, R.sup.2 is selected from the group consisting of --CH.sub.2 CH.sub.3, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, --C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, whereby R.sup.1 and R.sup.2 are not the same, R.sup.3 is chloro and R.sup.4 is selected from the group consisting of chloro, and methyl. 2. A compound of claim 1, wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, and R.sup.2 is selected from the group consisting of --C.sub.2 H.sub.5, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, and C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, R.sup.3 is chloro, and R.sup.4 is selected from the group consisting of chloro, and methyl. 3. A compound of claim 1, wherein R.sup.1 is --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, R.sup.2 is --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, R.sup.3 is chloro, and R.sup.4 is selected from the group consisting of chloro, and methyl. 4. A method for treating arterial hypertension in a mammal suffering therefrom, comprising administering to said mammal an amount effective to relax the vascular smooth muscle of said mammal of a compound of formula I ##STR14## wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OCH.sub.2 H.sub.5, R.sup.2 is selected from the group consisting of --CH.sub.2 CH.sub.3, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, --C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, whereby R.sup.1 and R.sup.2 are not the same, R.sup.3 is chloro, and R.sup.4 is selected from the group consisting of chloro, and methyl. 5. A method according to claim 4, wherein a compound of formula I is administered, wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, and R.sup.2 is selected from the group consisting of --C.sub.2 H.sub.5, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, and C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, R.sup.3 is chloro and R.sup.4 is selected from the group consisting of chloro, and methyl. 6. A method according to claim 4, wherein a compound of formula I is administered, wherein R.sup.1 is --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, R.sup.2 is selected from the group consisting of --CH.sub.2 C.tbd.CH, --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, R.sup.3 is chloro and methoxy, and R.sup.4 is selected from the group consisting of chloro, and methyl. 7. Pharmaceutical preparation, which comprises as an active ingredient a therapeutically effective dose of an antihypertensive compound having vascular smooth muscle relaxing properties which compound has the formula I ##STR15## wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, R.sup.2 is selected from the group consisting of --CH.sub.2 CH.sub.3, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, --C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, whereby R.sup.1 and R.sup.2 are not the same, R.sup.3 is chloro, and R.sup.4 is selected from the group consisting of chloro, and methyl, in association with a pharmaceutically acceptable carrier. 8. A pharmaceutical preparation according to claim 7, wherein the active ingredient is a compound of formula I, wherein R.sup.1 is selected from the group consisting of --CH.sub.3, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, and R.sup.2 is selected from the group consisting of --C.sub.2 H.sub.5, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3, --CH(CH.sub.3)C.sub.2 H.sub.5, --CH(CH.sub.3)CH.sub.2 OCH.sub.3, and C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3, R.sup.3 is chloro and R.sup.4 is selected from the group consisting of chloro and methyl. 9. A pharmaceutical preparation according to claim 7, wherein the active ingredient is a compound of formula I, wherein R.sup.1 is --CH.sub.3, --C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 OCH.sub.3, and --CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, R.sup.2 is selected from the group consisting of --CH.sub.2 C(CH.sub.3).dbd.CH.sub.2, R.sup.3 is chloro, and R.sup.4 is selected from the group consisting of chloro, and methyl. 10. A pharmaceutical preparation according to claim 7, wherein the substituted 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylic acid-diester compound comprises 0.1 to 99% by weight of the preparation. 11. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-ethylester. 12. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-ethylester-5-(2-methoxyethylester). 13. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-isopropylester. 14. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methyl-5-tert.butylester. 15. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-(2-methoxy-1-methylethylester). 16. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(2-methoxyethyl)ester-5-isopropylester. 17. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(2-ethoxyethyl)ester-5-ethylester. 18. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-(2-methoxy-1,1-dimethylethyl)ester. 19. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(2-methoxy)ethylester-5-propargyl ester. 20. The compound according to claim 1 which is 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-(2-methyl)allylester. 21. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-ethylester. 22. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-ethylester-5-(2-methoxyethylester). 23. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-isopropylester. 24. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methyl-5-tert.butylester. 25. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-(2-methoxy-1-methylethylester). 26. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(2-methoxyethyl)ester-5-isopropylester. 27. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(2-ethoxyethyl)ester-5-ethylester. 28. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-(2-methoxy-1,1-dimethylethyl)ester. 29. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(2-methoxy)ethylester-5-propargyl ester. 30. A pharmaceutical preparation according to claim 7 wherein said active ingredient is the compound 2,6-dimethyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-(2-methyl)allylester.