BENZODIAZEPINE RECEPTOR-BINDING ACTIVITY OF 8-SUBSTITUTED-9-(3-SUBSTITUTED-BENZYL)-6-(DIMETHYLAMINO)-9H-PURINES

被引：28

作者：

KELLEY, JL ^{[1
]}

MCLEAN, EW ^{[1
]}

LINN, JA ^{[1
]}

KROCHMAL, MP ^{[1
]}

FERRIS, RM ^{[1
]}

HOWARD, JL ^{[1
]}

机构：

[1] BURROUGHS WELLCOME CO,DIV PHARMACOL,RES TRIANGLE PK,NC 27709

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 01期

关键词：

D O I：

10.1021/jm00163a032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 8-substituted analogues of 9-(3-aminobenzyl)-6-(dimethylamino)-9if-purine (8) were synthesized and tested for their ability to bind to the benzodiazepine receptor (BZR) in rat brain tissue. The most active compound was the 8-bromo-9-(3-formamidobenzyl) analogue 16 (IC50= 0.011 µM), which was 1000-fold more active than the parent 9-benzyl-6-(dimethylamino)-9H-purine (1) and nearly as active as diazepam. Although substitution of a m-formamido group and an 8-bromo substituent on 1 imparted potent BZR binding activity, neither 16 nor 11 analogues exhibited significant anxiolytic activity on a modified Geller-Seifter conflict schedule. © 1990, American Chemical Society. All rights reserved.

引用

页码：196 / 202

页数：7

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