Stjernlöf P, Ennis M D, Hansson L O, Hoffman R L, Ghazal N B, Sundell S, Smith M W, Svensson K, Carlsson A, Wikström H
Department of Pharmacology, Göteborg University, Sweden.
J Med Chem. 1995 Jun 9;38(12):2202-16. doi: 10.1021/jm00012a021.
A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 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, D2, and D3 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.
制备了一系列针对强效5-羟色胺1A（5-HT1A）的1-、3-和4-取代类似物，以8-(二丙基氨基)-6,7,8,9-四氢-3H-苯并[e]吲哚-1-甲醛（5）为对照，并在体外对5-HT1A、5-HT1Dα、5-HT1Dβ、D2和D3受体进行了测试，还在体内对利血平预处理大鼠进行了5-羟色胺酸（5-HTP）和多巴积累试验以检测激动剂活性。部分化合物进行了拆分。1-位所使用的取代基是从由列表变量以及通过半经验方法（PM3）和分子力学软件（MMX）计算出的变量构建的主成分分析（PCA）图中选取的。在所制备的类似物中，有些，例如化合物21，在5-HT1A效应方面与化合物5等效。所有化合物对5-HT1A受体或多或少都具有选择性，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。
