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.

Abstract

Diarylpyrazoles like (VIII) and (X) are synthesized by Claisen condensation of acetophenone (I) with ethyl acetates (II), coupling of diketones (III) with aryl hydrazines (IV), and treatment of diarylpyrazole (V) with methanesulfonyl chloride (VII) to give the desired pharmacophores (VIII). Additionally, some parent methanesulfonamides, e.g. (VIIIa), are N-acylated. 1,3-Diarylpyrazoles are also formed in minor quantities. Acetanilides (VI) can be hydrolyzed to amines (V). The 4-methanesulfonamide group provides a few potent and selective inhibitors of COX-2 with inhibitory concentration values up to 30 nM, cf. (VIIIa) (some yields not given). -(SINGH*, S. K.; VOBBALAREDDY, S.; SHIVARAMAKRISHNA, S.; KRISHNAMRAJU, A.; RAJJAK, S. A.; CASTURI, S. R.; AKHILA, V.; RAO, Y. K.; Bioorg. Med. Chem.

Transformations of 3-aryl-2-chloro-2-imidoylaziridines: novel entries to 4-chloro-2,5-diaryl-1H-imidazoles and 2-chloro-2-acylaziridines

“…21,26 Previously, 4-bromo-and 4-fluoro-1H-pyrazoles were generated by condensation of 2-bromo-or 2-fluoro-1,3-propanediones and phenylhydrazines. 27,28 A drawback of the latter procedure was the formation of mixtures of isomers when unsymmetrical propane-1,3-dione derivatives were used.…”