1,3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPAR gamma partial agonists
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초록

A new series of PPAR gamma partial agonists, 1,3-diphenyl-1H-pyrazole derivatives, were identified using an improved virtual screening scheme combining ligand-centric and receptor-centric methods. An in vitro assay confirmed the nanomolar binding affinity of 1,3-diphenyl-1H-pyrazole derivatives such as SP3415. We also characterized the competitive antagonism of SP3415 against rosiglitazone at micromolar concentrations. They showed a PPAR gamma partial agonistic activity similar to that of a known PPAR gamma drug, pioglitazone, in a cell-based transactivation assay. Furthermore, the structure-activity relationships of the pyrazole derivatives were investigated through comparative molecular field analysis and binding mode analysis, which provided new insight concerning their partial agonistic effect on PPAR gamma. (C) 2010 Elsevier Ltd. All rights reserved.

키워드

PyrazolePeroxisome proliferators-activated receptor (PPAR)Comparative molecular field analysis (CoMFA)Computer-aided drug discoveryMolecular dockingBinding mode analysisACTIVATED-RECEPTOR-GAMMASELECTIVE INHIBITORDRUG DESIGNCOMFAIDENTIFICATIONDOCKINGQSARTHIAZOLIDINEDIONESOPTIMIZATIONTELMISARTAN
제목
1,3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPAR gamma partial agonists
저자
Choi, JiwonPark, YunsunLee, Hui SunYang, YoungYoon, Sukjoon
DOI
10.1016/j.bmc.2010.09.068
발행일
2010-12
유형
Article
저널명
Bioorganic and Medicinal Chemistry
18
23
페이지
8315 ~ 8323