BCL-2 FAMILY PROTEIN INHIBITORS, THEIR CYCLODEXTRIN INCLUSION COMPOUNDS, COMPLEXES, AND USES IN MANUFACTURE OF BCL-2 FAMILY PROTEIN INHIBITORS THEREOF

摘要

New Bcl-2 family protein inhibitors, their cyclodextrin inclusion compounds, cyclodextrin complexes, and the uses in the manufacture of BH3 analogs, Bcl-2 family protein inhibitors thereof are disclosed. The acenaphthoheterocycle compounds are obtained by introducing oxy-compounds, thio-compounds, carbonyl compounds, ester compounds or acyl compounds on the 3, 4, 6 positions of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile respectively, or the 9-carbonitrile furthermore being substituted to obtain acid, ester, amine or amide compounds, and obtained by reacting the acenaphthylenequinone with the methylene derivatives. They can simulate BH3-only protein, competitively bind and antagonize Bcl-2 and Mcl-1 proteins in vitro or intracellular, thereby inducing cell apoptosis. Furthermore, the cyclodextrin inclusion compounds and complexes can improve the effects. They all can be used in the manufacture of anticancer compounds.