2D quantitative structure-activity relationships (2D QSAR) studies were performed on a series of diarylcyclopentene derivatives as prostaglandin EP1 receptor antagonist. To establish the relationship between Prostaglandin EP1 receptor and diarylcyclopentene derivatives, a 2D-QSAR model based on individual, estate numbers, structural, electro topological and baumann alignment descriptors parameters was developed. The best model-1 correlation coefficient with r 2 = 0.8101, significant cross validated correlation coefficient (q 2 = 0.7491) and for external test set pred_r 2 = 0.7812 developed by Partial Least Squares method. The QSAR model reveals that hydroxyl and methoxy group at R position on the diarylcyclopentene moiety is responsible for improving the prostaglandin EP1 receptor activity. The results of 2D QSAR studies were used to design new molecules and to predict their prostaglandin EP1 receptor activity using the developed models.