Pyrido[1,2‐a]pyrimidin‐4‐ones: Ligand‐based Design, Synthesis, and Evaluation as an Anti‐inflammatory Agent

Abstract

In the present study, a series of novel pyrido[1,2‐a]pyrimidin‐4‐one derivatives (1–45) were synthesized, characterized, and evaluated for their anti‐inflammatory activity. The structures of all newly synthesized compounds were confirmed by 1H NMR, 13C NMR, mass spectroscopy, and C, H, and N analyses. Preliminary these newly synthesized compounds were evaluated for their in vitro cyclooxygenase (COX)‐2/COX‐1 inhibitory activity. The celecoxib, a COX‐2 inhibitor, was used as a reference standard drug. In this inhibitory study, compounds 42, 43, 44, and 45 were found to have significant in vitro inhibitory profile as compared with the reference drug. These compounds were then subjected to their in vivo anti‐inflammatory assay by using carrageenan‐induced rat paw edema method in next level of screening. Later, these same compounds were tested for their ulcerogenic property. Based on these activity data, the compound 43 (in vitro COX‐2 activity—IC50 = 0.4 μM, SI = 400, in vivo anti‐inflammatory activity—72% inhibition after 3 h, and 0.38%—Ulcer index) was emerged as most promising anti‐inflammatory agent with very low ulcerogenic action.