当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Computer-aided design of non sulphonyl COX-2 inhibitors: an improved comparative molecular field analysis incorporating additional descriptors and comparative molecular similarity indices analysis of 1,3-diarylisoindole derivatives.

Computer-aided design of non sulphonyl COX-2 inhibitors: an improved comparative molecular field analysis incorporating additional descriptors and comparative molecular similarity indices analysis of 1,3-diarylisoindole derivatives.

Abstract：

:A set of thirty five molecules of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindoles endowed with selective COX-2 inhibitory activity was analyzed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Besides conventional steric and electrostatic fields, seven additional descriptors were incorporated to the CoMFA models. An improved CoMFA model (r(2)(cv)=0.536, r(2)(conv)=0.968, SEE=0.222, r(2)(pred)=0.6564) was obtained by taking into account the CMR as additional descriptor. This analysis provided useful information regarding the pharmacophoric requirements for COX-2 inhibitory activity. FlexX was used to find out the binding orientation of this new class of 1,3-diaryl isoindoles in the active site of COX-2. The contour maps produced by improved CoMFA model was superimposed onto the active site revealing a good correlation between the contour maps and the active site residue interactions.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Chakraborti AK,Thilagavathi R

doi

10.1016/s0968-0896(03)00404-8

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

3989-96

issue

18

eissn

0968-0896

issn

1464-3391

pii

S0968089603004048

journal_volume

11

pub_type

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