STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE 8-AMINO-6,7,8,9-TETRAHYDRO-3H-BENZ[E]INDOLE RING-SYSTEM .1. EFFECTS OF SUBSTITUENTS IN THE AROMATIC SYSTEM ON SEROTONIN AND DOPAMINE-RECEPTOR SUBTYPES
STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE 8-AMINO-6,7,8,9-TETRAHYDRO-3H-BENZ[E]INDOLE RING-SYSTEM .1. EFFECTS OF SUBSTITUENTS IN THE AROMATIC SYSTEM ON SEROTONIN AND DOPAMINE-RECEPTOR SUBTYPES
复制标题
DOI：
10.1021/jm00012a021
复制
发表时间：
1995-06-09
影响因子：
7.3
通讯作者：
WIKSTROM, H
中科院分区：
文献类型：
--
作者：
STJERNLOF, P;ENNIS, MD;WIKSTROM, H
制备了一系列5-HT1a激动剂8-(dipropylamino)-6，7，8，9-tetrahydro-3H-benz[e]indole-1-carbaldehyde(5)的1、3和4-取代类似物，并在体外测试了5-HT1a、5-HT1Dα、5-HT1Dβ、D-2和D-3受体的激动剂活性，并在利血平处理的大鼠体内进行了5-羟色胺和多巴比妥钠蓄积试验。对部分化合物进行了拆分。用半经验方法(PM3)和分子力学软件(MMX)计算的变量和列表变量构成的主成分分析(PCA)图选择了1-位上使用的取代基。在所制备的类似物中，一些类似物，例如化合物21，在5-HT1A效应方面与化合物5相同。所有化合物都或多或少地对5-HT1a受体有选择性，但许多化合物对5-HT1Dα受体的亲和力高于对5-HT1Dβ受体的亲和力。
A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A agonist 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D-2, and D-3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but-many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors.