Synthesis and Anti-Inflammatory Activity of <i>N</i>(2)-Arylindazol-3(2<i>H</i>)-One Derivatives: Copper-Promoted Direct <i>N</i>-Arylation via Chan–Evans–Lam Coupling

Abstract

Inflammatory-related diseases are becoming increasingly prevalent, leading to a growing focus on the development of anti-inflammatory agents, with a particular emphasis on creating novel structural compounds. In this study, we present a highly efficient synthetic method for direct N-arylation to produce a variety of N(2)-arylindazol-3(2H)-ones 3, which exhibit anti-inflammatory activity. The Chan–Evans–Lam (CEL) coupling of N(1)-benzyl-indazol-3-(2H)-ones 1 with arylboronic acids 2 in the presence of a copper complex provided the corresponding N(2)-arylindazol-3(2H)-ones 3 in good-to-excellent yields, as identified with NMR, MS, and X-ray crystallography techniques. The cell viability and anti-inflammatory effects of the synthesized compounds (3 and 5) were briefly assessed using the MTT method and Griess assay. Among them, compounds 5 exhibited significant anti-inflammatory effects with negligible cell toxicity.

Keywords

• anti-inflammatory
• cytotoxicity
• indazol-3-ones
• <i>N</i>-arylation
• Chan–Evans–Lam coupling