Synthesis of l,4-Dihydropyridine-5-phosphonates and Their Calcium-Antagonistic and Antihypertensive Activities: Novel Calcium-Antagonist 2-[Benzyl(phenyl)amino]ethyl 5-(5,5-Dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate Hydrochloride Ethanol (NZ-105) and Its Crystal Structure1)

Abstract

The effect of the 3-carboxylic-ester variation in 2,2-dimethyltrimethylene 3-alkoxycarbonyl-4-aryl-l,4-dihydro-2,6-dimethyl-5-pyridinephosphonates (1) was investigated with relation to the calcium-antagonistic and antihypertensive activities: the analogs containing the alkyl groups of not more than 12 carbons and an amino functionality in the carboxylic-ester moiety were synthesized to be examined for biological activities. Among them, 2-[benzyl(phenyI)amino]-ethyl 5-(5,5-dimethyl-2-oxo-l,3,2-dioxaphosphorinan-2-yl)-l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridine-carboxylate hydrochloride ethanol (NZ-105) showed particularly beneficial activities and was selected for further pharmacological studies and clinical development. Some aspects of the structure-activity relationships and solid-state structure of NZ-105 by X-ray crystallographic analysis were described. © 1992, The Pharmaceutical Society of Japan. All rights reserved.