3D QSAR studies based in silico screening of 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine analogs for anti-inflammatory activity

•The 3D QSAR study was performed separately for two different series.•The developed 3D QSAR models were used to screen the designed compounds.•The ten compounds were selected based on their predicted activities for experimental studies.•The compounds 5c and 5f were found to be potent with highest in vivo anti-inflammatory activity.•The electron donating nature of R7 and SO2CH3 group at R9 in designed compounds is needed for higher activity.

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.

Graphical abstractIn silico screening of 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine analogs for anti-inflammatory activity was performed using 3D QSAR models developed for two different series for their in-vivo anti-inflammatory activity and in-vitro COX-2 inhibitory activity.Figure optionsDownload full-size imageDownload as PowerPoint slide