1265828-99-6

Basic information

• Product Name: 2-[2-oxo-2H-6-(4-isopropylphenoxy)acenaphthylen-1-ylidene]-malononitrile
• Synonyms: 2-[2-oxo-2H-6-(4-isopropylphenoxy)acenaphthylen-1-ylidene]-malononitrile
• CAS NO: 1265828-99-6
• Molecular Weight: 364.403
• Mol File: 1265828-99-6.mol

Chemical Properties

• CAS DataBase Reference: 2-[2-oxo-2H-6-(4-isopropylphenoxy)acenaphthylen-1-ylidene]-malononitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[2-oxo-2H-6-(4-isopropylphenoxy)acenaphthylen-1-ylidene]-malononitrile(1265828-99-6)
• EPA Substance Registry System: 2-[2-oxo-2H-6-(4-isopropylphenoxy)acenaphthylen-1-ylidene]-malononitrile(1265828-99-6)

Safety Data

• Hazardous Substances Data: 1265828-99-6(Hazardous Substances Data)

Upstream product

• 1265828-86-1 5‐(4‐isopropylphenoxy)acenaphthylene-1,2‐dione 
• 109-77-3 malononitrile 
• 26254-35-3 5-bromoacenaphthylene-1,2-dione 
• 82-86-0 acenaphthene quinone 

Downstream Products

• 1265829-18-2 3-(4-isopropylphenoxy)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile 
• 1416085-57-8 9-(butylamino)-3-(4-isopropylphenoxy)-8H-acenaphtho[1,2-b]pyrrol-8-one 
• 1416085-58-9 C₂₉H₃₀N₂O₂ 
• 1416085-59-0 3-(4-isopropylphenoxy)-9-(3-phenylpropylamino)-8H-acenaphtho[1,2-b]pyrrol-8-one 

Relevant articles and documents

3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1

Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9- carbonitrile (3, S1), a library of 9-substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure-activity relationship study, and site-directed mutation, compound 6d (3-(4- aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-3-phenyl)propylamine) was identified to span p2-p4 pockets of Mcl-1, Bcl-2 and Bcl-xL, and then exhibited 9- to 35-fold better affinity to the three targets than 3 (IC 50 = 10, 20 and 18 nM, respectively), which led to greater activity in induction of apoptosis in multiple cancer cell lines. Different contribution of p4 pocket to binding Bcl-2 and Mcl-1 was also investigated by plotting the potency and the HAC of the derivatives.

Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach

Based on a known nanomolar Bcl-2 homology domain 3 (BH3) mimetic 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b] pyrrole-9-carbonitrile (S1, MW: 331), we applied a fragment-based approach to obtain BH3 mimetics with improved affinity and improved solubility in a water-ethanol (9:1) cosolvent. After the deconstruction of 1 (S1), we obtained fragment cyanoacetamide (4), which was determined to be a ligand efficiency (LE) hot part. After a rational optimization through fragment evolution beginning with fragment 4, a smaller Mcl-1 inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g, MW: 288) with a 6-fold increase in affinity compared to 1 was obtained, as predicted by our optimization curve and identified by Mcl-1 protein nuclear magnetic resonance (NMR).

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

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.