NOVEL 2-AMINO-1,4-DIHYDROPYRIDINE CALCIUM-ANTAGONISTS .2. SYNTHESIS AND ANTIHYPERTENSIVE EFFECTS OF 2-AMINO-1,4-DIHYDROPYRIDINE DERIVATIVESHAVING N,N-DIALKYLAMINOALKOXYCARBONYL GROUPS AT 3-POSITION AND OR 5-POSITION/

Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N-dia lkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synth esized and their antihypertensive effects were evaluated in spontaneou sly hypertensive rats, Remarkably prolonged duration of antihypertensi ve action was observed when a tertiary amino group was introduced into either the 3- or 5-ester side-chain of the 1,4-dihydropyridine ring, In particular, the compounds containing cyclic amino moieties at the 3 -position showed greater potency than those with acyclic amino moietie s, Chemical modification studies indicated that the two ester side-cha ins of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities, 3-( 1-Benzhydrylazetidin-3-yl) 5-isopropyl thyl-4-(3-nitrophenyl)-3,5-pyri dine-dicarboxylate, I-43 (CS-905), exhibited potent and long-lasting a ntihypertensive effects with gradual onset of action, and is a promisi ng candidate as an antihypertensive drug.