The 3D QSAR studies based on generation of common pharmacophore hypotheses (CPHs) were performed separately for the series of 1,2,3,4-tetrahydropyrimidin-5-yl-acetic acid and 2-(4-sulfonylphenyl)pyrimidine analogs for their in-vivo anti-inflammatory activity and in-vitro COX-2 inhibitory activity respectively. The main idea of selecting two different series was to develop two 3D QSAR models for same scaffold (1,2,3,4-tetrahydropyrimidine/pyrimidine) for same target, but with different aspects of activity. The aim of study was to screen designed compounds and select new compounds with increased COX-2 selectivity. The best 3D QSAR model from both group was employed as 3D search query to screen the designed 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine derivatives. The new compounds showing good predicted activity were selected for experimental studies. Among the synthesized compounds, 5c and 5f showed highest anti-inflammatory activity.