Synthesis and antihypertensive activity of 1,4-dihydropyridine derivatives with a 4-(disubstituted phenyl) ring and an aminoalkyl ester group: highly potent and long-lasting calcium antagonists.
New 1,4-dihydropyridine derivatives bearing a 4-(disubstituted phenyl) ring and an aminoethyl ester or an amino-2,2-dimethyl-propyl ester were synthesized and their antihypertensive activities were examined in normotensive rats and spontaneously hypertensive rats. The effects of phenyl substituents and ester groups on the antihypertensive activity are discussed. Several compounds showed a more potent antihypertensive activity than nicardipine and most compounds had a longer duration of action. Among them, 7B.HCl (TC-81) showed highly potent and long-lasting activity and was selected as a candidate for further pharmacological investigations.
Kanno
H
H
Teijin Institute for Bio-Medical Research, Tokyo, Japan.
Yamaguchi
H
H
Okamiya
Y
Y
Sunakawa
K
K
Takeshita
T
T
Naruchi
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; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines