Novel 2-amino-1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having N,N-dialkylaminoalkoxycarbonyl groups at 3- and/or 5-position.
Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N,-dialkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their antihypertensive effects were evaluated in spontaneously hypertensive rats. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced into either the 3- and/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 moieties. Chemical modification studies indicated that the two ester side-chains of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities. 3-(1-Benzhydrylazetidinited potent and long-lasting antihypertensive effects with gradual onset of action, and is a promising candidate as an antihypertensive drug.
Kobayashi
T
T
Pharmaceutical Research Department, Ube Laboratory, Ube Industries, Ltd. Yamaguchi, Japan.
Inoue
T
T
Nishino
S
S
Fujihara
Y
Y
Oizumi
K
K
Kimura
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine