Synthesis of N2-(substituted benzyl)-3-(4-methylphenyl)indazoles as novel anti-angiogenic agents.
To search for novel compounds with potent anti-angiogenic activity, a series of N(1)-(substituted benzyl)-3-(4-methylphenyl)-1H-indazoles (16, 18, 20, 22, 24, 26, 28, 30, 32) and N(2)-(substituted benzyl)-3-(4-methylphenyl)-2H-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)-1H-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-1H-indazol-3-yl)benzoate (YD-3). Among these tested compounds, 2-(4-chlorobenzyl)-3-(4-methylphenyl)-2H-indazole (19), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2H-indazole (25), and 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2H-indazole (31) showed significant anti-angiogenic activity and are worthy of further investigation.
Huang
Li-Jiau
LJ
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
Shih
Mei-Ling
ML
Chen
Hua-Sin
HS
Pan
Shiow-Lin
SL
Teng
Che-Ming
CM
Lee
Fang-Yu
FY
Kuo
Sheng-Chu
SC
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013057:Spectrum Analysis / Q000379:methods
D020533:Angiogenesis Inhibitors; D007093:Imidazoles