1158183-65-3Relevant academic research and scientific papers
ACENAPHTHO HETEROCYCLE COMPOUNDS, CYCLODEXTRIN INCLUSION COMPOUNDS AND COMPLEXES, AND USES IN THE MANUFACTURES OF BH3 PROTEIN ANALOGUE, BCL-2 FAMILY PROTEIN INHIBITORS THEREOF
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Page/Page column 7, (2011/10/10)
The present invention relates to acenaphtho heterocyclic compounds, cyclodextrin inclusion compounds and complexes thereof, and their uses in manufacturing the inhibitors of BH3 analogue, Bcl-2 family proteins. The acenaphtho heterocyclic compounds are obtained by introducing oxo-, thio-, carbonyl, ester or acyl in the 3-, 4- and 6-position of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile, or further substituting 9-cyano with carboxyl, ester or amide. The compounds can simulate BH3-only protein, competitively binding and antagonizing Bcl-2, Bcl-XL and Mcl-1 proteins in vitro or intracellularly, to induce cell apoptosis. The cyclodextrin inclusion compounds and complexes can improve the effects. Therefore, they can all be used in the manufacture of anticancer compounds.
3-Thiomorpholin-8-oxo-8 h -acenaphtho[1,2- b ]pyrrole-9-carbonitrile (S1) based molecules as potent, dual inhibitors of B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1): Structure-based design and structure-activity relationship studies
Zhang, Zhichao,Wu, Guiye,Xie, Feibo,Song, Ting,Chang, Xilong
, p. 1101 - 1105 (2011/04/25)
We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure-activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-1, from which a novel dual inhibitor 3-(4-aminophenylthio)-8-oxo-8H- acenaphtho[1,2-b]pyrrole-9-carbonitrile (6h) was obtained, which showed significant enhanced IC50 value against Mcl-1 (5 nM), greater Mcl-1/Bak disruption potential, and accordingly a 10-fold increased cytotoxicity over 3.
ACENAPHTHO HETEROCYCLE COMPOUNDS, CYCLODEXTRIN INCLUSION COMPOUNDS AND COMPLEXES, AND USES IN THE MANUFACTURES OF BH3 PROTEIN ANALOGUE, BCL-2 FAMILY PROTEIN INHIBITORS THEREOF
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Page/Page column 4-5, (2011/10/19)
The present invention relates to acenaphtho heterocyclic compounds, cyclodextrin inclusion compounds and complexes thereof, and their uses in manufacturing the inhibitors of BH3 analogue, Bcl-2 family proteins. The acenaphtho heterocyclic compounds are ob
