Tiapamil, Ro 11-1781, a Ca++ antagonist. An improved synthesis, physiochemical properties, preparation of a deuterated derivative.
An improved synthesis of tiapamil 3, Ro 11-1781, N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2- propylamine 1,1,3,3-tetraoxide is described. The structure of the corresponding hydrochloride monohydrate 4, a Ca++ antagonist has been confirmed by an X-ray crystallographic analysis. Since biotransformation of tiapamil into metabolites 5, 6 and 7 occurs mainly in the close vicinity of the nitrogen atom, compound 8 bearing seven deuterium atoms has been synthesised.
D000818:Animals; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003903:Deuterium; D004285:Dogs; D006801:Humans; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism; D011437:Propylamines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D013976:Tiapamil Hydrochloride
D002121:Calcium Channel Blockers; D011437:Propylamines; D003903:Deuterium; D013976:Tiapamil Hydrochloride