QSAR studies of prostaglandin analogs as D2 receptor antagonist

In this study, a QSAR (Quantitative Structure Activity Relationship) analysis was carried out by using 80 indole derivatives synthesized by Toda et.al.. These prostaglandin D2 (PGD2) receptor antagonists exhibit strong PGD2 receptor binding and blocked cyclic adenosine 3?, 5?-monophosphate (cAMP) formation in vitro. When given orally, these compounds dramatically suppress allergic inflammatory responses via increase of vascular permeability.The whole data set was divided into a training set (70 compounds) and a test set (10 compounds) randomly. Heuristic Method and The Best Multi-Linear Regression (BMLR) method in CODESSA 2.7.2 were used to select the most appropriate molecular descriptors from a large set of descriptors and develop a linear QSAR model.The resulting five-parameter model with Heuristic Method produced squared cross-validation correlation coefficient (R2CV) of 0.7130 and 0.6684 for the training and test sets, respectively. However, five-parameter model with BMLR gave correlation values (R2) of 0.7195 and 0.7227 for the training and test sets, respectively. QSAR analysis revealed that relative negative charge on N atom and the minimum net atomic charge on the compounds were more significant factors for receptor binding. In addition, inhibitor activity of the compounds was also increases with increasing H-Bonding Surface Area.