1158183-67-5

Basic information

• Product Name: 2-[2-oxo-2H-6-(p-tolyloxy)acenaphthylen-1-ylidene]-malononitrile
• Synonyms: 2-[2-oxo-2H-6-(p-tolyloxy)acenaphthylen-1-ylidene]-malononitrile
• CAS NO: 1158183-67-5
• Molecular Weight: 336.349
• Mol File: 1158183-67-5.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 2-[2-oxo-2H-6-(p-tolyloxy)acenaphthylen-1-ylidene]-malononitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[2-oxo-2H-6-(p-tolyloxy)acenaphthylen-1-ylidene]-malononitrile(1158183-67-5)
• EPA Substance Registry System: 2-[2-oxo-2H-6-(p-tolyloxy)acenaphthylen-1-ylidene]-malononitrile(1158183-67-5)

Safety Data

• Hazardous Substances Data: 1158183-67-5(Hazardous Substances Data)

Upstream product

• 1158183-77-7 5-(p-tolyloxy)acenaphthenequinone 
• 109-77-3 malononitrile 
• 26254-35-3 5-bromoacenaphthylene-1,2-dione 
• 82-86-0 acenaphthene quinone 

Downstream Products

• 1158183-49-3 3-(p-tolyloxy)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile 
• 1158183-52-8 4-(p-methylphenoxy)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile 

Relevant articles and documents

ACENAPHTHO HETEROCYCLE COMPOUNDS, CYCLODEXTRIN INCLUSION COMPOUNDS AND COMPLEXES, AND USES IN THE MANUFACTURES OF BH3 PROTEIN ANALOGUE, BCL-2 FAMILY PROTEIN INHIBITORS THEREOF

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.

Probing the difference between BH3 groove of Mcl-1 and Bcl-2 protein: Implications for dual inhibitors design

Based on our previous discovery of a dual inhibitor of Mcl-1 and Bcl-2, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (1, S1), and guided by structure insight of 1 complex with Mcl-1 and Bcl-2, we exploited the spatial orientation of BH3 groove of the two proteins by a series of analogues of 1. These analogues contain substitutes with various steric hindrance designed to explore the width and length of the p2 pocket. The structure-activity relationships (SARs) studies together with docking studies and cell-based assays proved that the p2 pocket of Mcl-1 is relatively wider and shorter than that of Bcl-2. A novel dual inhibitor 6 was obtained based on these new findings that it exhibited nanomalar affinities toward Mcl-1 and Bcl-2, as well as nanomalar cytotoxicity activity against multiple cancer cell lines.