earticle

영어

Chemoattractant Receptor Homologous molecule expressed on Th2 cells (CRTh2) is a chemoattractant receptor with seven transmembrane helices targeted for inflammatory diseases such as asthma and allergic rhinitis. In this study, pharmacophore based Comparative Molecular Similarity Indices Analysis (CoMSIA) were performed on the series of 2- (2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids derivatives. Initially, GASP module was used for generation of pharmacophore models using five highly active compounds from the dataset. Among the generated pharmacophores, the best pharmacophore model was selected based on fitness score and was used as template for the alignment of compounds which was used for CoMSIA analysis. The best predictions were obtained utilizing steric, hydrophobic and H-bond acceptor parameters showing a q2= 0.559 and r2= 0.730. 15 test set compounds was used to investigate the predictive ability of the CoMSIA model. Contour maps suggested that presence of bulky substituents and H-bond acceptor atoms at 5th position of benzene ring will increase the activity of the compounds. The results obtained from this study will be useful to design more potent CRTh2 antagonists.