NOVEL HETEROCYCLIC-ANALOGS OF THE NEW POTENT CLASS OF CALCIUM ENTRY BLOCKERS - 1-[[4-(AMINOALKOXY)PHENYL]SULFONYL]INDOLIZINES

被引:135
作者
GUBIN, J
DEVOGELAER, H
INION, H
HOUBEN, C
LUCCHETTI, J
MAHAUX, J
ROSSEELS, G
PEIREN, M
CLINET, M
POLSTER, P
CHATELAIN, P
机构
[1] Sanofi Research Center, B-1120 Brussels, 1, avenue de Béjar
关键词
D O I
10.1021/jm00062a015
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Several heterocyclic analogues of the potent 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines were synthesized and evaluated for their antagonistic calcium activities in comparison with the 1-sulfonylindolizine SR 33557 and the usual calcium antagonist references verapamil, cis-(+)-diltiazem, and nifedipine. The bicyclic nine-membered rings were, in general, more potent than the bicyclic 10-membered or five-membered rings. Among the bicyclic nine-membered rings, the indole nucleus appeared to be extremely favorable to support the calcium antagonistic activity. In particular, compound 36, with an IC50 value for the inhibition of [H-3]nitrendipine equal to 0.072 nM, is among the most potent calcium antagonist known. This compound has been selected for clinical development.
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页码:1425 / 1433
页数:9
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