Pharmacophoric 2-hydroxyalkyl benzenesulfonamide: a single-step synthesis from benzenesulfonamide via hemiaminal.

ortho-Acylation attempt of benzenesulfonamide afforded the corresponding hemiaminal as major product. The in situ reduction of the reaction mixture, reported herein, directly provided 2-hydroxyalkyl benzenesulfonamide, an important pharmacophoric element for designing drug-like scaffolds. Its application is demonstrated through designing a novel series of 1,5-diarylpyrazoles for cyclooxygenase-2 (COX-2) inhibition.

Methanesulfonamide group at position-4 of the C-5-phenyl ring of 1,5-diarylpyrazole affords a potent class of cyclooxygenase-2 (COX-2) inhibitors.

The effect of methanesulfonamide (MeSO(2)NH) group on COX-2 inhibitory activity of 1,5-diarylpyrazole is described. While this group being at position-4 of the N(1)-phenyl ring was found to be ineffective, its installation at position-4 of the C-5 phenyl ring offered several potent and selective inhibitors of COX-2 with IC(50) as low as 30 nM.