Mining the Chemical Abstracts database with pharmacophore-based queries

被引：6

作者：

Bremner, JB

Castle, K

Griffith, R ^{[1
]}

Keller, PA

Ridley, DD

机构：

[1] Univ Newcastle, Sch Environm & Life Sci, Callaghan, NSW 2308, Australia

[2] Univ Wollongong, Dept Chem, Wollongong, NSW 2522, Australia

[3] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

来源：

JOURNAL OF MOLECULAR GRAPHICS & MODELLING | 2002年 / 21卷 / 03期

基金：

英国医学研究理事会;

关键词：

computer-aided drug design; 3D pharmacophore; 2D query; SciFinder Scholar((R)); database mining; high-throughput virtual screening; selective antagonists; alpha(1)-adrenoceptor subtypes;

D O I：

10.1016/S1093-3263(02)00141-9

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

A method is described to convert 3D patterns of pharmacophoric groups into 2D queries for molecular substructure searches of the Chemical Abstracts database with SciFinder Scholar(R). The results of such searches and the options for refinement of the hit lists are presented using a rigid tetrahydroisoquinoline-carbazole (IQC) hybrid molecule fitted onto previously developed pharmacophores for subtype-selective alpha(1)-adrenergic receptor antagonists as an example. The compounds retrieved were further analysed by limiting their physical properties to 'drug-like' ranges and by enumerating the ring skeletons they contain. Selected ring skeletons were evaluated by fitting them on to the original pharmacophores. Several structurally novel rigid ring skeletons were found with this new database mining technique which are potentially useful as leads in the design Of alpha(1B) selective adrenergic receptor antagonists. (C) 2002 Elsevier Science Inc. All rights reserved.

引用

页码：185 / 194

页数：10

共 13 条

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