Abstract:So far,as reported in literature,there are two kinds of CDK7 inhibitors,one is cyclin-dependent protein kinase inhibition factor(CKI),and the other is small molecular compounds.During small molecular compounds, 3-(1H-indol-2-yl)- 1H -indazole has the most activation both in vivo and vitro and is deep researched.when it is nitrile group substituted in the indazole 6- position,it has the best activation,the IC50 is only 11nM.In our project, 3-(1H-indol-2-yl)-1H-indazole was kept as primary backbone,replaced 4-C in the indole ring with N,and the substituted side chains were systematically revised according to the drug design principle as:bioisosterism,ring analogs and the others.In this way,several kinds of target compounds were designed and synthesized as the CDK7 inhibitor.
Keywords：CDK7 inhibitor;antitumor;computer simulation;indazole-4azaindole
