| abstract |
The present invention relates to acenaphtho heterocyclic compounds, their inclusion compounds and complexes with cyclodextrin and their uses in the manufacture of protein inhibitors of the Bcl-2 family, analogs of BH3. The heterocyclic acenaphtho compounds are obtained by introducing oxo-, thio-, carbonyl, ester or acyl groups at positions 3-, 4- and 6- of the 8-oxo-8H-acenaphto [1,2-b] pyrrole-9- carbonitrile or the subsequent substitution of the 9-cyano group with carboxyl, ester or amide. The compounds can simulate BH3-only protein, bind competitively and antagonize Bcl-2, Bcl-XL and Mcl-in vitro proteins or intracellularly, to induce cell apoptosis. Inclusion compounds and cyclodextrin complexes can improve the effects. Therefore, they can be used in the manufacture of antineoplastic compounds. |