Synthesis of N2-(substituted benzyl)-3-(4-methylphenyl)indazoles as novel anti-angiogenic agents

Abstract

To search for novel compounds with potent anti-angiogenic activity, a series of N 1-(substituted benzyl)-3-(4-methylphenyl)-1 H-indazoles ( 16, 18, 20, 22, 24, 26, 28, 30, 32) and N 2-(substituted benzyl)-3-(4-methylphenyl)-2 H-indazoles ( 17, 19, 21, 23, 25, 27, 29, 31, and 33) were synthesized. The structures of these regioisomers were established by IR, UV, and NMR spectral data. 3-(4-Methylphenyl)-1 H-indazole ( 6) and the N 2-substituted derivatives ( 17, 19, 21, 23, 25, 29, 31, 33) were evaluated for their anti-angiogenic activity. Most of them showed more prominent activity than ethyl 4-(1-benzyl-1 H-indazol-3-yl)benzoate ( YD- 3). Among these tested compounds, 2-(4-chlorobenzyl)-3-(4-methylphenyl)-2 H-indazole ( 19), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2 H-indazole ( 25), and 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2 H-indazole ( 31) showed significant anti-angiogenic activity and are worthy of further investigation.