STRUCTURE ACTIVITY RELATIONSHIP STUDIES OF CENTRAL-NERVOUS-SYSTEM AGENTS .5. EFFECT OF THE HYDROCARBON CHAIN ON THE AFFINITY OF 4-SUBSTITUTED 1-(3-CHLOROPHENYL)PIPERAZINES FOR 5-HT1A RECEPTOR-SITE

被引:50
作者
MOKROSZ, JL
PIETRASIEWICZ, M
DUSZYNSKA, B
CEGLA, MT
机构
[1] Institute of Pharmacology, Polish Academy of Sciences
关键词
D O I
10.1021/jm00091a004
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The effect of the hydrocarbon chain of the model 4-substituted 1-(3-chlorophenyl)piperazines 12-31 on their affinity for 5-HT1A receptor sites was investigated. It was found that elongation of the 4-n-alkyl chain strongly increases the 5-HT1A affinity of the investigated compounds. The affinity reaches the maximum (K(i) = 2.67 nM) for the n-hexyl derivative 20. It was shown that hydrophobic interactions of N-4 substituents of 1-arylpiperazines significantly contribute to their 5-HT1A affinity. The specific binding constant was defined as the receptor affinity of the protonated species of compounds under physiological conditions. The range of K(i)AH+ = 1-3 X 10(-11) M is a specific affinity limit of the investigated class of compounds at the 5-HT1A receptor sites.
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页码:2369 / 2374
页数:6
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