172462-88-3

Basic information

• Product Name: 4(1H)-Quinazolinone, 8-hydroxy-2-(4-nitrophenyl)- (9CI)
• Synonyms: 4(1H)-Quinazolinone, 8-hydroxy-2-(4-nitrophenyl)- (9CI)
• CAS NO: 172462-88-3
• Molecular Formula: C₁₄H₉N₃O₄
• Molecular Weight: 0
• Mol File: 172462-88-3.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 4(1H)-Quinazolinone, 8-hydroxy-2-(4-nitrophenyl)- (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 4(1H)-Quinazolinone, 8-hydroxy-2-(4-nitrophenyl)- (9CI)(172462-88-3)
• EPA Substance Registry System: 4(1H)-Quinazolinone, 8-hydroxy-2-(4-nitrophenyl)- (9CI)(172462-88-3)

Safety Data

• Hazardous Substances Data: 172462-88-3(Hazardous Substances Data)

Upstream product

• 181135-49-9 8-methoxy-2-(4-nitrophenyl)quinazolin-4-one 
• 106782-78-9 3-methoxy-2-aminobenzamide 
• 122-04-3 4-nitro-benzoyl chloride 
• 3177-80-8 2-amino-3-methoxybenzoic acid 
• 220115-16-2 3-methoxy-2-(4-nitrobenzamido)benzamide 

Relevant articles and documents

Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases

Tankyrases (TNKSs), members of the PARP (Poly(ADP-ribose)polymerases) superfamily of enzymes, have gained interest as therapeutic drug targets, especially as they are involved in the regulation of Wnt signalling. A series of 2-arylquinazolin-4-ones with varying substituents at the 8-position was synthesised. An 8-methyl group (compared to 8-H, 8-OMe, 8-OH), together with a 4′-hydrophobic or electron-withdrawing group, provided the most potency and selectivity towards TNKSs. Co-crystal structures of selected compounds with TNKS-2 revealed that the protein around the 8-position is more hydrophobic in TNKS-2 compared to PARP-1/2, rationalising the selectivity. The NAD+-binding site contains a hydrophobic cavity which accommodates the 2-aryl group; in TNKS-2, this has a tunnel to the exterior but the cavity is closed in PARP-1. 8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one was identified as a potent and selective inhibitor of TNKSs and Wnt signalling. This compound and analogues could serve as molecular probes to study proliferative signalling and for development of inhibitors of TNKSs as drugs.

Quinazolinone compounds

Phosphate derivatives are disclosed of quinazolinone compounds having structural formula (I) or a pharmaceutically acceptable salt thereof, wherein X' represent hydroxyl, alkyl, alkoxy, or O-Z where Z is a phosphate or phosphate derivative; Y' represents

Novel benzimidazole and quinazolinone inhibitors of the DNA repair enzyme Poly(ADP-ribose)polymerase

Two novel series of inhibitors of the DNA repair enzyme poly(ADP-ribose)polymerase (PARP) were synthesized and evaluated for biological activity. In the benzimidazole-4-carboxamide series, the carbamoyl function was restricted into the putative biologically active conformation via an intramolecular hydrogen bond, while for quinazolin-4-[3H]-ones this was achieved by incorporation of the group into a heterocyclic ring. For both series of compounds, syntheses involved acylation of substituted anthranilic acid derivatives, followed by acid- or base-catalysed cyclization. 8-Hydroxyquinazolin-4-[3H]-ones were prepared from the corresponding 8-methoxy compounds by dealkylation with boron tribromide. PARP inhibitory activity was determined in permeabilized L1210 murine leukaemia cells, in comparison with the established inhibitor 3-hydroxybenzamide (IC50 = 8.3 μM). For both series, inhibitory activity varied with the nature of the 2-substituent, with benzimidazole-4-carboxamides proving approximately tenfold more potent than the previously prepared benzoxazole-4-carboxamides. 2-Arylbenzimidazoles were especially active, and 2-(4-methoxyphenyl)benzimidazole-4-carboxamide (IC50 = 60 nM) is the most potent PARP inhibitor reported to date. In the quinazolinone series, a 2-(4-nitrophenyl) substituent, and either an 8-methyl or 8-hydroxy group conferred potent inhibitory activity, with IC50 values of 0.13 and 0.23 μM, respectively, being observed.