QSAR of Pyrazole Oxadiazole Derivatives as s1p1 Agonists Studied by CoMFA, CoMSIA and Docking

Author(s): Baokun Li, Tingjun Hou, Chongqian Zhang, Youyong Li.

Journal Name: Letters in Drug Design & Discovery

Volume 10 , Issue 9 , 2013

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Abstract:

S1P1 is an important target from GPCR family, whose crystal structure was released recently. Here, for the first time, we perform the 3D-QSAR analyses on a series of pyrazole oxadiazole derivatives, which are potent S1P1 agonists, by CoMFA and CoMSIA. We use two basic common cores, oxadiazole and pyrazole-oxadiazole, to align all compounds to establish the models of COMFA and COMSIA. The best CoMFA model by applying region focusing achieved a q2 of 0.736 and an r2 of 0.968. The actual predictive capabilities of the best CoMFA and CoMSIA models were then confirmed by the satisfactory predictions for the test set: rpred 2=0.762 for the best CoMFA model. Moreover, the contour maps derived from the best CoMFA and CoMSIA models are consistent with the biological activities of the studied compounds. Our results provide structural details about the interaction between S1P1 and small ligands. Our study is useful in guiding future design of more promising inhibitors of S1P1.

Keywords: QSAR, drug design, S1P1, GPCR, CoMFA, CoMSIA.

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Article Details

VOLUME: 10
ISSUE: 9
Year: 2013
Page: [836 - 852]
Pages: 17
DOI: 10.2174/15701808113109990001
Price: $58

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