| Summary: | 碩士 === 中國醫藥學院 === 藥物化學研究所 === 90 === In order to search novel compounds with potent antiplatelet and antiangiogenesis activities, 3-(4-methylphenyl)-1H-indazole (6) was used as the key intermediate and its derivatives were synthesized.
In the presence of triethylamine, 1-(N-morpholino)cyclohexene was reacted with 4-methylbenzoyl chloride. Followed by hydrolysis using dil. hydrochloric acid, 2-oxocyclohexyl 4-methylphenyl ketone (4) was obtained. 3-(4-Methylphenyl)-4,5,6,7-tetrahydro-1H-indazole (5) was gained after reaction of compound 4 and hydrazine. The product, 3-(4-methyl phenyl)-1H-indazole (6), was obtained after compound 5 was oxygenated by catalytic dehydrogenation on Pd/C. Finally, benzylation of compound 6 with various substituted benzyl chloride produced the derivatives, 1-(substituted benzyl)-3-(4-methylphenyl)-1H-indazoles (7、9、11、13、15、16、18) and 2-(substituted benzyl)-3-(4-methyl phenyl)-2H-indazoles (8、10、12、14、17、19 - 21).
Compound 6 and its related compounds were evaluated for their biological activities. Most of N2-substituted derivatives (8、10、12、14、17、19、20、21) showed more prominent antiplatelet activity than N1-substituted derivatives (9、11、13、15、16). Among these N2-substituted derivatives, 2-(4-chlorobenzyl)-3-(4-methylphenyl)-2H-indazole (8), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2H-indazole (14) and 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2H-indazole (19) showed significant antiangiogenesis and worthy for further investigation.
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