172462-89-4

Basic information

• Product Name: 4(1H)-Quinazolinone, 8-methoxy-2-phenyl- (9CI)
• Synonyms: 4(1H)-Quinazolinone, 8-methoxy-2-phenyl- (9CI);8-METHOXY-2-PHENYLQUINAZOLIN-4(3H)-ONE
• CAS NO: 172462-89-4
• Molecular Formula: C₁₅H₁₂N₂O₂
• Molecular Weight: 252.27
• Mol File: 172462-89-4.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 4(1H)-Quinazolinone, 8-methoxy-2-phenyl- (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 4(1H)-Quinazolinone, 8-methoxy-2-phenyl- (9CI)(172462-89-4)
• EPA Substance Registry System: 4(1H)-Quinazolinone, 8-methoxy-2-phenyl- (9CI)(172462-89-4)

Safety Data

• Hazardous Substances Data: 172462-89-4(Hazardous Substances Data)

Upstream product

• 172462-99-6 2-benzamido-3-methoxybenzamide 
• 106782-78-9 3-methoxy-2-aminobenzamide 
• 98-88-4 benzoyl chloride 
• 3177-80-8 2-amino-3-methoxybenzoic acid 
• 90-04-0 2-methoxy-phenylamine 
• 5395-00-6 N-(2-methoxyphenyl)benzamide 
• 709030-49-9 4-(N,N-dimethylamino)-8-methoxy-2-phenylquinazoline 

Relevant articles and documents

Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors

Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly selective Aurora A inhibitors is difficult because Aurora A and B share high homology and differ only by three residues in their ATP-binding pockets. Through structure-based drug design, we designed and synthesized a series of novel quinazolin-4-amine derivatives. These derivatives act as selective Aurora A kinase inhibitors by exploiting the structural differences between Aurora A and B. The selectivities of most compounds were improved (the best up to >757-fold) when comparing with the lead compound (3-fold). In vitro biochemical and cellular assays revealed that compound 6 potently inhibited Aurora A kinase and most human tumor cells. Furthermore, compound 6 effectively suppressed carcinoma, such as triple-negative breast cancers (TNBC) in an animal model. Therefore, compound 6 might serve as a promising anticancer drug. Moreover, through molecular dynamic (MD) analysis, we have identified that a salt bridge formed in Aurora B is key contributor for the isoform selectivity of the inhibitor. This salt bridge has not been previously detected in the reported crystal structure of Aurora B. These results might provide a crucial basis for the further development of highly potent inhibitors with high selectivity for Aurora A.

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.

TANKYRASE INHIBITORS

The present invention relates to a compound of formula I wherein X is C(R6) or N, Y is C or N, and ring A, ring B, R1 and R2 have the meanings defined herein, provided that when ring B is carbocyclic, X is C(R6); or a pharmaceutically acceptable salt or solvate thereof. The compounds are tankyrase-1 and tankyrase-2 inhibitors and are useful in the treatment of a number of conditions, including cancer.

Macrocylic Inhibitors of Hepatitis C Virus

Compounds of the formula I: and N-oxides, salts, and stereoisomers thereof wherein A is OR1, NHS(═O)pR2; wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl;R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl;p is independently 1 or 2;n is 3, 4, 5 or 6; — denotes an optional double bond;L is N or CRz; Rz is H or forms a double bond with the asterisked carbon;Rq is H or when L is CRz, Rq can also be C1-C6alkyl;Rr is quinazolinyl, optionally substituted with one two or three substituents each independently selected from C1-C6 alkyl, C1-C6alkoxy, hydroxyl, halo, haloC1-C6alkyl, amino, mono- or dialkylamino, mono- or dialkylaminocarbonyl, C1-C6alkyl-carbonylamino, C0-C3alkylenecarbocyclyl and C0-C3 alkyleneheterocyclyl;R5 is hydrogen, C1-C6alkyl, C1-C6alkoxyC1-C6alkyl or C3-C7cycloalkyl;R6 is hydrogen, C1-C6alkyl, C1-C6alkoxy, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl, hydroxy, bromo, chloro or fluoro have utility in the treatment or prophylaxis of flaviviral infections such as HCV

MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS

Inhibitors of HCV replication of formula (I), and the N-oxides, salts, and stereoisomers thereof, wherein each dashed line represents an optional double bond; X is Ν, CH and where X bears a double bond it is C; R1a and R1b are hydrogen, C3-7cycloalkyl, aryl, Het, C1-6alkoxy, C1-6alkyl optionally substituted with halo, C1-6alkoxy, cyano, polyhaloC11-6alkoxy, C3-7cycloalkyl, aryl, or with Het; or R1a and R1b together with the nitrogen to which they are attached form a 4 to 6 membered heterocyclic ring which may be optionally substituted; L is a direct bond, -O- , -O-C1-4alkanediyl-, -O-CO-, -O-C(=O)-ΝR5a - or -O -C(=O)-NR5a-C1-4alkanediyl-; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl, amino, mono- or diC1-6alkylamino; R4 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from O, S and N, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents; and Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S , being optionally condensed with a benzene ring, and wherein Het may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS

Inhibitors of HCV replication of formula (I), the N-oxides, salts, and stereochemically isomeric forms thereof, wherein each dashed line (represented by -------) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted on any carbon or nitrogen ring atom with one, two, three, or four substituents; L is a direct bond, -O-. -O-C1-4alkanediyl-, -O-C(=O)-, -O-C(=O)-NR4a- or -O-C(=O)-NR4aC1-4alkanediyl-; R2 is hydrogen, -OR5, -C(O)OR5, -C(=O)R6, -C(=O)NR4aR4b, -C(=O)NHR4c,-NR4aR4b, -NHR4c, -NR4aSOpNR4aR4b, -NR4aSOpR7, or B(OR5)2; R3 is hydrogen, and where X is C or CH, R3 may also be C1-6alkyl; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents ; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

The Synthesis of 8-Hydroxyquinazoline Derivatives and Their Acid-Base Interactions

The reaction of N-(2-R1-oxyphenyl)benzimidoyl chlorides with cyanamide derivatives in the presence of titanium tetrachloride as a catalyst has yielded some new 4-amino-8-R1-oxy-2-phenylquinazolines. pK a values have been determined for these compounds and the influence of substituents at the basicity of the parent system has been discussed. Some investigations on the methyl-quinazolinyl ether cleavage in different medium have been done yielding the appropriate hydroxyquinazoline derivatives. In those cases when the deprotection of 4-amino-8-methoxy-2-phenylquinazoline was carried in aqueous acidic solutions, the formation of the hydrolysis products 3,4-dihydro-2-phenyl-4-quinazolone derivatives was observed as well.

Methods, compounds and compositions for treating gout

This invention relates to methods of preventing, treating or lessening verity of gout by administration of PARP inhibitors.

Resistance-modifying agents. 5.1 Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP)

Clinical studies concerning the role of poly(ADP-ribose) polymerase (PARP) in the repair of drug- and radiation-induced DNA damage have been impeded by the poor solubility, lack of potency, and limited specificity of currently available inhibitors. A seri

Benzamide analogs useful as PARP (ADP-ribosyltransferase, ADPRT) DNA repair enzyme inhibitors

A range of 3-oxybenzamide compounds and related quinazolinone compounds are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. The compounds disclosed include 3-benzyloxybenzamides, 3-oxybenzamides in which a chain of 5 or more methylene groups terminate in a halogen atom or in a purin-9-yl moiety, certain benzoxazole-4-carboxamide compounds and certain quinazolinone compounds. In formula X and Y together may form a bride -X-Y- that represents the grouping (a), (b) or (c )wherein R5 is H, alkyl, aryl or aralkyl.