Synthesis and pharmacological study of diphenylalkylamines with cycloaliphatic residues. New coronary vasodilators.
The paper describes the synthesis and the pharmacological evaluation of some derivatives of prenylamine, all with a cycloaliphatic ring within or instead of the isopropylamine moiety. Their general formulas are: (C6H5)2CH-CH2-CH2-NH-CH-CH2-R CH2 (I) (C6H5)2CH-CH2-CH2-NH-R' (II) where R contains and R' is a cycloaliphatic ring. Several compounds and particularly those of formula (I), and of formula (II), where the alicyclic ring had a bulky substituent in para were more active than prenylamine as coronary vasodilators on isolated guinea-pig heart (Langendorff). The most interesting derivative was M.G. 8926 [N-(3,3-diphenylpropyl)-alpha-methyl-beta-cyclohexylethylamine], which was more active than prenylamine on Langendorff's heart and in enhancing the pressor response to catecholamines and inhibiting the isoprenaline induced hypotension. Moreover, it had almost the same effects as prenylamine as spasmolytic, local and general anesthetic, on heart rate and arterial pressure and against coronary spasm from pitressin.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010276:Parasympatholytics; D011299:Prenylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis*
D010276:Parasympatholytics; D014665:Vasodilator Agents; D011299:Prenylamine