PYRIMIDO[5,4-B]INDOLE DERIVATIVES .1. A NEW CLASS OF POTENT AND SELECTIVE ALPHA-1 ADRENOCEPTOR LIGANDS

被引：67
|
作者：
RUSSO, F [1 ]
ROMEO, G [1 ]
GUCCIONE, S [1 ]
DEBLASI, A [1 ]
机构：
[1] IST RIC FARMACOL MARIO NEGRI, CONSORZIO MARIO NEGRI SUD, I-66030 SANTA MARIA IMBARO, ITALY
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 06期
关键词：
D O I：
10.1021/jm00110a014
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A number of 3-substituted pyrimido[5,4-b]indole-2,4-diones (7-23) were evaluated for their in vitro alpha-1 adrenoceptor affinity by radioligand receptor binding assays. Some compounds bearing a (phenylpiperazinyl)alkyl side chain were potent alpha-1 adrenoceptor ligands. The most active derivative in displacement of [H-3]prazosin from rat cortical membranes was 3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]pyrimido[5,4-b]indole-2,4-dione (10) (K(i) = 0.21 nM). Discrete modifications in the structure resulted in higher selectivity (> 10 000 times) for alpha-1 than alpha-2, beta-2, and 5HT1A receptors. Some compounds also had affinity for the 5HT1A receptor. The most selective alpha-1 ligand was 3-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]pyrimido[5,4-b]indole-2,4-dione (13).
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收藏
页码：1850 / 1854
页数：5
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