ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

QSAR study of 2,4-disubstituted phenoxyacetic acid derivatives as a CRTh₂ receptor antagonists

Abhishek K. Jain, Veerasamy Ravichandran, Rajesh Singh, Vishnukanth Mourya, and Ram K. Agrawal

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, 470 003 Madhy Pradesh, India

E-mail: dragrawal2001@yahoo.co.in

Received: 21 July 2008  Revised: 6 December 2008  Accepted: 12 December 2008

Abstract: In pursuit of better CRTh₂ receptor antagonist agents, QSAR studies were performed on a series of 2,4-disubstituted phenoxyacetic acid derivatives. Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The best QSAR model was selected; having the correlation coefficient R = 0.904, standard error of estimation SEE = 0.456 and the cross validated squared correlation coefficient Q ² = 0.739. Predictive ability of the selected model was also confirmed by the leave one out cross validation method and by leave 33 % out Q ² = 0.688. The QSAR model indicates that the descriptors (logP, SI3, LM, and DVZ) play an important role in the CRTh₂ receptor antagonist activities. Results of the present study may be useful in the designing of more potent 2,4-disubstituted phenoxyacetic acid derivatives as CRTh₂ receptor antagonist agents.

Keywords: QSAR - 2,4-disubstituted phenoxyacetic acid derivatives - CRTh₂ receptor antagonist - multiple linear regression

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-009-0030-x

Chemical Papers 63 (4) 464–470 (2009)