[Synthesis and comparative pharmacological studies of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylates with non-identical ester functions (author's transl)].
Michael-addition of 3-aminocrotonic acid ester 7 to aralkylidene acetoacetic acid esters 6 is followed by ring closure to give novel 4-aryl-1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylates 8 with non-identical ester functions. In the series of 3-nitrophenyl derivatives (8, Ar=3-nitrophenyl) the pharmacological activities (coronary vasodilation, antihypertensive activity) of the asymmetrically substituted derivatives are shown to be superior to those of the corresponding symmetrically substituted derivatives in many cases. One representative of this class 3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (nitrendipine, Bay e 5009, No. 3) was selected for further development as an antihypertensive drug.