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
Kyungmin Kim,
Jeong Ho Kim,
Heejae Choi,
Byeongno Lee,
Jihyun Lee,
Kang Min Ok,
Tae Hoon Lee,
Hakwon Kim
Affiliations
Kyungmin Kim
Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi, Republic of Korea
Jeong Ho Kim
Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi, Republic of Korea
Heejae Choi
Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi, Republic of Korea
Byeongno Lee
Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi, Republic of Korea
Jihyun Lee
Department of Chemistry, Sogang University, Seoul 04107, Republic of Korea
Kang Min Ok
Department of Chemistry, Sogang University, Seoul 04107, Republic of Korea
Tae Hoon Lee
Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi, Republic of Korea
Hakwon Kim
Department of Applied Chemistry, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin-si 17104, Gyeonggi, Republic of Korea
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.
