Efficient Synthesis and In Vitro Biological Evaluation of 2,5‐Diaryloxazoles as Potential Nitric Oxide Production Inhibitors

An efficient first synthesis of 2,5‐diaryloxazoles 1 – 5 was accomplished from commercially inexpensive precursors and in overall yields of 38–48%. The synthesis proceeds via α‐aminoketones and cyclodehydration (Robinson–Gabriel reaction) as key step. Next, these oxazoles were examined for their inhibitory effect against nitric oxide (NO) production in lipopolysaccharide (LPS)‐induced RAW 264.7 cells and were found to display concentration‐dependent inhibition of NO production without cytotoxicity. Of note, compound 3 (70.7%; IC 50 = 2.33 μM) was identified as a potent inhibitor in view of its comparable inhibitory effect with the positive control, N G ‐monomethyl‐L‐arginine acetate (L‐NMMA) (79.3%; IC 50 = 4.51 μM) followed by compounds 5 (68.3%; IC 50 = 2.30 μM) and 2 (53.9%; IC 50 = 6.31 μM). As a whole, compound 3 may hold great promise for further development of NO production targeted anti‐inflammatory agent.