TY - JOUR
T1 - Dihydropyrimidines
T2 - Novel Calcium Antagonists with Potent and Long-Lasting Vasodilative and Antihypertensive Activity
AU - Cho, Hidetsura
AU - Ueda, Masaru
AU - Shima, Keivuu
AU - Mizuno, Akira
AU - Havashimatsu, Mariko
AU - Ohnaka, Yoshiko
AU - Takeuchi, Yumi
AU - Hamaguchi, Mikiko
AU - Aisaka, Kazuo
AU - Hidaka, Toshinori
AU - Kawai, Masanori
AU - Takeda, Minako
AU - Ishihara, Takafumi
AU - Funahashi, Kazuteru
AU - Satoh, Fumio
AU - Morita, Minoru
AU - Noguchi, Teruhisa
PY - 1989/10/1
Y1 - 1989/10/1
N2 - The novel calcium antagonists 3-N-substituted-3,4-dihydropyrimidines 1 and 9 and 3-N-substituted-dihydro-pyrimidin-2(lH)-ones 8 were regioselectively synthesized in good yields. Compounds 1 [especially 1s [R1= (CH2)2 N(benzyl)(2-naphthylmethyl), R2= i-Pr, X = o-NO2] and It [R1= (CH2)2 N(benzyl)(3,4-dichlorobenzyl), R2= i-Pr, X = o-n O2]] exhibited not only more potent and longer lasting vasodilative action but also a hypotensive activity with slow onset as compared with dihydropyridines. Moreover, some dihydropyrimidines [lq [R1= (CH2)2 N(benzyl)(3-phenylpropyl), R2= CH2(cyclopropyl), X = o-NO2], Is, and It] were weaker in blocking atrioventricular conduction in anesthetized open-chest dogs and less toxic than the dihydropyridines.
AB - The novel calcium antagonists 3-N-substituted-3,4-dihydropyrimidines 1 and 9 and 3-N-substituted-dihydro-pyrimidin-2(lH)-ones 8 were regioselectively synthesized in good yields. Compounds 1 [especially 1s [R1= (CH2)2 N(benzyl)(2-naphthylmethyl), R2= i-Pr, X = o-NO2] and It [R1= (CH2)2 N(benzyl)(3,4-dichlorobenzyl), R2= i-Pr, X = o-n O2]] exhibited not only more potent and longer lasting vasodilative action but also a hypotensive activity with slow onset as compared with dihydropyridines. Moreover, some dihydropyrimidines [lq [R1= (CH2)2 N(benzyl)(3-phenylpropyl), R2= CH2(cyclopropyl), X = o-NO2], Is, and It] were weaker in blocking atrioventricular conduction in anesthetized open-chest dogs and less toxic than the dihydropyridines.
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U2 - 10.1021/jm00130a029
DO - 10.1021/jm00130a029
M3 - Article
C2 - 2552119
AN - SCOPUS:0024427853
VL - 32
SP - 2399
EP - 2406
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 10
ER -