708-73-6

Usage

InChI:InChI=1/C9H6ClNO2/c1-5-11-8-4-6(10)2-3-7(8)9(12)13-5/h2-4H,1H3

Upstream product

• 108-24-7 acetic anhydride 
• 89-77-0 2-Amino-4-chlorobenzoic acid 
• 823-57-4 2-bromo-5-chloroaniline 
• 827-66-7 N-(2-bromo-5-chlorophenyl)acetamide 
• 78-39-7 Triethyl orthoacetate 
• 66909-52-2 2,4-dichlorobenzoic acid potassium salt 
• 50-84-0 2,4 dichlorobenzoic acid 

Downstream Products

• 7012-88-6 7-chloro-2-methylquinazolin-4(3H)-one 
• 90537-62-5 3-amino-7-chloro-2-methyl-4(3H)-quinazoline 
• 5900-56-1 2-acetylamino-4-chlorobenzoic acid 
• 340734-91-0 7-chloro-2-[2-(4-chloro-phenyl)-vinyl]-benzo[d][1,3]oxazin-4-one 
• 894-49-5 7-chloro-2-methyl-3-o-tolyl-3H-quinazolin-4-one 
• 340735-02-6 7-chloro-2-[2-(2-nitro-phenyl)-vinyl]-benzo[d][1,3]oxazin-4-one 
• 98601-72-0 (2-amino-4-chloro-phenyl)-(2-chloro-phenyl)-methanone 
• 25648-19-5 2-Amino-4-chlorobenzhydrol 
• 35001-99-1 7-chloro-2-methylsulfanyl-4-phenyl-4H-benzo[d][1,3]thiazine 
• 4076-50-0 2-amino-4-chlorobenzophenone 
• 25648-20-8 7-chloro-4-phenyl-1,4-dihydro-benzo[d][1,3]thiazine-2-thione 
• 1073340-43-8 7-chloro-3-(4-[(1-cyclobutyl-4-piperidinyl)oxy]phenyl)-2-methyl-4(3H)-quinazolinone 
• 72889-32-8 4-(7-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)benzoic acid 

Relevant academic research and scientific papers

Pd-Catalyzed Carbonylative Synthesis of 4H-Benzo[d][1,3]Oxazin-4-Ones Using Benzene-1,3,5-Triyl Triformate as the CO Source

A facile synthesis of 4H-benzo[d][1,3]oxazin-4-one derivatives by Pd-catalyzed carbonylative cross-coupling between N-(ortho-bromoaryl)amides and benzene-1,3,5-triyl triformate (TFBen) was developed. This procedure does not require the toxic and flammable gas CO as the carbonyl source and tolerates a wide scope of functional groups. Remarkably, 4H-benzo[d][1,3]oxazin-4-ones incorporated to natural products and drugs can be constructed by this method.

Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases

Aberrant activation of FMS-like tyrosine receptor kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML) in 20–30% of patients. In this study we identified a highly selective (phenylethenyl)quinazoline compound family as novel potent inhibitors of the FLT3-ITD and FLT3-D835Y kinases. Their prominent effects were confirmed by biochemical and cellular proliferation assays followed by mice xenograft studies. Our modelling experiments and the chemical structures of the compounds predict the possibility of covalent inhibition. The most effective compounds triggered apoptosis in FLT3-ITD AML cells but had either weak or no effect in FLT3-independent leukemic and non-leukemic cell lines. Our results strongly suggest that our compounds may become therapeutics in relapsing and refractory AML disease harboring various ITD and tyrosine kinase domain mutations, by their ability to overcome drug resistance.

4H-Benzo[d][1,3]oxazin-4-ones and Dihydro analogs from substituted anthranilic acids and orthoesters

A one-pot route to 2-alkyl and 2-aryl-4H-benzo[d][1,3]oxazin-4-ones (also known as 4H-3,1-benzoxazin-4-ones) has been developed and studied. The method involves the reaction of aryl-substitutedanthranilic acidswithorthoesters inethanol catalyzedby acetic acid. Additionally,wehave also investigated the reaction under microwave conditions. Not all of the substrates were successful in yielding the target heterocycles as some of the reactions failed to undergo the final elimination. This process led to the isolation of (±)-2-alkyl/aryl-2-ethoxy-1,2-dihydro-4H-benzo[d][1,3]oxazin-4-ones. The formation of the dihydro analogs correlated with the electron density on the aromatic ring: Electron-donating groups favored the 4H- benzo[d][1,3]oxazin-4-ones, while electron-withdrawing groups tended to favor the dihydro product. Substituting a pyridine ring for the benzene ring in the substrate acid suppressed the reaction.

Synthesis and bioactivities evaluation of novel vv-pyridylpyrazole derivatives with 1,2,3-triazole and quinazolin-4(3H)-one substructures

Two series of JV-pyridylpyrazole derivatives containing 1,2,3-triazole and quinazolin-4(3H)-one substructures were designed and synthesized. In total, 18 novel compounds were prepared, and all compounds were characterized by 1H NMR, 13C NMR and elemental

Distinct novel quinazolinone exhibits selective inhibition in MGC-803 cancer cells by dictating mutant p53 function

The mutant p53 proteins and their corresponding cellular response can be manipulated by novel quinazolinone derivatives 4-8 (a-i) in p53 mutant cancer cells. Of the two most potent compounds, 4a exhibited promising broad-spectrum anti-cancer effects, whereas 6c showed selective and exclusive inhibition activity in p53 mutant cancer cell lines but low toxicity to wild-type p53 cancer cell A375 and normal lung fibroblast WI-38 cells. Furthermore, 6c exhibited a more sophisticated mechanism for cell-destructive response by causing S/G2 phase arrest effect and cell size reduction. Compared with the cellular response of 6b and genetic background of cell lines studied, p53 mutation was found to be the key factor and main target for 6c evoked cell-destructive response. Molecular mechanism studies indicated that p53 phosphorylation and acetylation dual-targeting inhibitor 6c exerted anti-cancer activities with a special mechanism in evoking cell apoptosis by arresting mutant p53 function to trigger the deregulation of Cdk2 caused Bim-mediated apoptosis. To the best of our knowledge, 6c is the first quinazolinone derivative to dictate mutant p53 function for apoptotic cell death.

Reactivity of 2-methyl-4H-3,1-benzoxazin-4-ones and 2-methyl-4H-pyrido[2,3- d][1,3]oxazin-4-one under microwave irradiation conditions

The reactivity of variably substituted 2-methyl-4H-3,1-benzoxazin-4-ones and 2-methyl-4H-pyrido[2,3-d][1,3]oxazin-4-one towards carbon and oxygen nucleophiles under microwave irradiation conditions was investigated. Optimization of the reaction conditions of oxazinones with carbon nucleophiles led to the synthesis of a series of 4-hydroxy-quinolin-2-ones and 4-hydroxy-1,8-naphthyridin-2-ones in high yields, whereas reaction with a variety of alcohols proceeded smoothly to the formation of the corresponding N-acetyl-anthranilates and nicotinates.

Quinazolin-4-one derivatives: A novel class of noncompetitive NR2C/D subunit-selective N-methyl-D-aspartate receptor antagonists

We describe a new class of subunit-selective antagonists of N-methyl d-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives is noncompetitive and voltage-independent, suggesting that this family of compounds does not exert action on the agonist binding site of the receptor or block the channel pore. The compounds described here resemble CP-465,022 ((S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl] -6-fluoro-3H-quinazolin-4-one), a noncompetitive antagonist of AMPA-selective glutamate receptors. However, modification of ring substituents resulted in analogues with greater than 100-fold selectivity for recombinant NMDA receptors over AMPA and kainate receptors. Furthermore, within this series of compounds, analogues were identified with 50-fold selectivity for recombinant NR2C/D-containing receptors over NR2A/B containing receptors. These compounds represent a new class of noncompetitive subunit-selective NMDA receptor antagonists.

Atropisomeric quinazolin-4-one derivatives are potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists

Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure-activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.

1H and 13C NMR spectral studies of some 4H-3,1-benzoxazin-4-ones and their 2-acylaminobenzoic acid precursors

The 1H and 13C NMR spectra of twelve 4H-3,1-benzoxazine-4-ones and of their acylaminobenzoic acid precursors are presented. Differentiation between these two series of compounds is best achieved through the characteristic JCH coupling interactions in the high frequency carbonyl region. Some 4H-pyrido[2,3-d][1,3]oxazin-4-ones have also been studied and some earlier literature assignments revised.

Synthesis of 5-chloro-2-methyl-3-(5-methylthiazol-2-yl)-4(3H)-quinazolinone and related compounds with potential biological activity

Eight new 2-methyl-4(3H)-quinazolinones (8a-8d, 9c, 9d, 10c, 10d) with one or two chlorine atoms in the benzene ring and a 5-methyl-1,3-thiazol-2-yl, 4-methyl-1,3-thiazol-2-yl, and 5-ethyl-1,3,4-thiadiazol-2-yl substituent in position 3 of the heterocyclic ring were synthesized and characterized. The two step procedure (Scheme 1) utilizes chlorosubstituted anthranilic acids (3a-3d) and acetic anhydride as the starting materials, with the respective chlorosubstituted 2-methyl-4H-3,1-benzoxazin-4-ones (4a-4d) as the intermediates. The quinazoline derivatives were characterized by their melting points, elemental analyses and the mass, ultraviolet, infrared, and 1H and 13C nmr spectra. The new compounds are expected to be biologically active.