16499-57-3

Basic information

• Product Name: 7-Fluoro-4-quinazolone
• Synonyms: 7-FLUOROQUINAZOLIN-4-OL;BUTTPARK 76\07-32;7-Fluoro-4-quinazolone;7-Fluoroquinazolin-4(3H)one;4(3H)-Quinazolinone, 7-fluoro-;7-fluoro-4(3H)-quinazolinone(SALTDATA: FREE);7-Fluoroquinazolin-4-one;7-Fluoroquinazolin-4(1H)-one, 7-Fluoroquinazolin-4-ol, 3,4-Dihydro-7-fluoro-4-oxoquinazoline
• CAS NO: 16499-57-3
• Molecular Formula: C₈H₅FN₂O
• Molecular Weight: 164.1365032
• Product Categories: API intermediates;Fused Ring Systems
• Mol File: 16499-57-3.mol

Chemical Properties

• Melting Point: 246.0 to 250.0 °C
• Boiling Point: 293.3 °C at 760 mmHg
• Flash Point: 131.2 °C
• Appearance: /
• Density: 1.44 g/cm³
• Vapor Pressure: 0.00174mmHg at 25°C
• Refractive Index: 1.642
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 0.51±0.20(Predicted)
• CAS DataBase Reference: 7-Fluoro-4-quinazolone(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Fluoro-4-quinazolone(16499-57-3)
• EPA Substance Registry System: 7-Fluoro-4-quinazolone(16499-57-3)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 16499-57-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
7-Fluoro-4-quinazolone is used as a key intermediate in the preparation of the aurora kinase inhibitor AZD1152 (A808100) for its role in inhibiting PARP-1 activity. This makes it a valuable component in the development of cancer therapeutics, as PARP inhibitors have shown promise in treating various types of cancer by exploiting the DNA repair mechanisms of cancer cells.
Additionally, 7-Fluoro-4-quinazolone's PARP-1 inhibitory activity suggests its potential use in the development of other cancer treatments that target this enzyme, which plays a crucial role in DNA repair and is often dysregulated in cancer cells. This makes it a promising candidate for further research and development in oncology.

InChI:InChI=1/C8H5FN2O/c9-5-1-2-6-7(3-5)10-4-11-8(6)12/h1-4H,(H,10,11,12)

Upstream product

• 446-32-2 4-fluoroanthranilic acid 
• 3473-63-0 formamidine acetic acid 
• 6313-33-3 formamidine hydrochloride 
• 77287-34-4 formamide 
• 117324-05-7 2-amino-4-fluoro-benzoic acid ethyl ester 
• 463-52-5 formamidine 
• 2475-81-2 methyl 4-fluoroanthranilate 
• 64-18-6 formic acid 
• 106754-80-7 4-fluoro-2-nitrobenzamide 
• 394-01-4 4-fluoro-2-nitrobenzoic acid 
• 67-56-1 methanol 
• 119023-25-5 4-fluoroanthranilamide 
• 162012-66-0 7-fluoro-4-[(3-methylphenyl)-amino]-6-nitroquinazoline 

Downstream Products

• 16499-62-0 4-chloro-7-fluoroquinazoline 
• 162012-69-3 7-fluoro-6-nitro-3H-quinazolin-4-one 
• 196194-86-2 7-(2-methoxyethoxy)-3,4-dihydroquinazolin-4-one 
• 557770-89-5 4-(3-phenylpropylamino)-7-(2-chloroethoxy)quinazoline 
• 557770-88-4 2-(5-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-2H-pyrazol-3-yl)-N-(2,3-difluorophenyl)acetamide 
• 722544-46-9 2-(5-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-2H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide 
• 557770-93-1 N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(2-hydroxymethyl)pyrrolidin-1-yl]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 
• 722544-51-6 N-(3-fluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 
• 722544-37-8 di-tert-butyl {(2R)-1-[3-({4-[(5-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl phosphate 
• 722544-50-5 di-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate 
• 957881-03-7 2-{ethyl[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)proplyl]amino}ethyl dihydrogen phosphate 
• 557770-90-8 4-chloro-7-(3-chloropropoxy)quinazoline 
• 557770-91-9 2-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)acetic acid 
• 199327-54-3 4-chloro-7-(2-methoxyethoxy)quinazoline 

Relevant articles and documents

Synthesis and Biological Evaluation of Quinazolonethiazoles as New Potential Conquerors towards Pseudomonas Aeruginosa

Novel quinazolonthiazoles were designed and synthesized as new potential antimicrobial agents by facile multi-step procedure from o-aminobenzoic acids and 2-acetylthiazole. A series of biological evaluation showed that compound 7d was the most effective quinazolonethiazole with superior activity to reference drugs chloramphenicol and norfloxacin. This active molecule displayed unobvious bacterial resistance against P. aeruginosa, the low toxicity to normal hepatocytes, suitable pharmacokinetics and drug-likeness. The preliminary biological interaction suggested that quinazolonethiazole 7d might induce bacterial death by disturbing the membrane permeability, whilst preventing bacteria from growth by integrating into DNA and binding with topoisomerase IV. These findings provided significant background for the further development of quinazolonethiazoles as new potential drugs in combating drug-resistant pathogens.

Discovery of 4-aminoquinazoline - Urea derivatives as Aurora kinase inhibitors with antiproliferative activity

Two series of 20 novel 4-aminoquinazoline - urea derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activity against six human cancer cell lines (K562, U937, A549, NCI-H661, HT29 and LoVo) using the MTT-based assay. Most compounds showed significant antiproliferative activities against four solid tumor cell lines, but no or poor activities against two leukemia cell lines. Furthermore, the target compounds were screened for Aurora A/B kinases inhibitory activity. Among them, 7c, 7d, 8c, and 8d are more potent against Aurora A kinase than ZM447439. Docking study of compounds 7d and ZM447439 revealed that they bound strongly to the ATP-binding sites of Aurora A and B. Thus, they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting Aurora kinases.

Identification of Unique Quinazolone Thiazoles as Novel Structural Scaffolds for Potential Gram-Negative Bacterial Conquerors

A class of quinazolone thiazoles was identified as new structural scaffolds for potential antibacterial conquerors to tackle dreadful resistance. Some prepared compounds exhibited favorable bacteriostatic efficiencies on tested bacteria, and the most representative 5j featuring the 4-trifluoromethylphenyl group possessed superior performances against Escherichia coli and Pseudomonas aeruginosa to norfloxacin. Further studies revealed that 5j with inappreciable hemolysis could hinder the formation of bacterial biofilms and trigger reactive oxygen species generation, which could take responsibility for emerging low resistance. Subsequent paralleled exploration discovered that 5j not only disintegrated outer and inner membranes to induce leakage of cytoplasmic contents but also broke the metabolism by suppressing dehydrogenase. Meanwhile, derivative 5j could intercalate into DNA to exert powerful antibacterial properties. Moreover, compound 5j gave synergistic effects against some Gram-negative bacteria in combination with norfloxacin. These findings indicated that this novel structural type of quinazolone thiazoles showed therapeutic foreground in struggling with Gram-negative bacterial infections.

Synthesis and biological evaluation of a new class of quinazolinone azoles as potential antimicrobial agents and their interactions with calf thymus DNA and human serum albumin

A series of novel quinazolinone azoles were synthesized and characterized by NMR, IR, MS and HRMS spectra. Bioactive assays showed that some target compounds exhibited significant antimicrobial potency. Especially, nitroimidazole derivative 3a displayed comparable or even superior antibacterial efficacies (MIC = 0.03-0.05 μmol mL-1) in contrast with norfloxacin (MIC = 0.01-0.05 μmol mL-1) and chloromycin (MIC = 0.02-0.10 μmol mL-1). The preliminary interactive investigations of compound 3a with calf thymus DNA by UV-vis spectroscopy revealed that compound 3a could bind to DNA to form compound 3a-DNA complex by an intercalative mode and further block DNA replication to exert powerful antibacterial and antifungal activities. Hydrogen bonds and van der Waals forces played important roles in the association of compound 3a-HSA.

Development of a Robust Scale-Up Synthetic Route for BPR1K871: A Clinical Candidate for the Treatment of Acute Myeloid Leukemia and Solid Tumors

Herein, a robust and scalable procedure for the synthesis of multikinase inhibitor BPR1K871 (1, a quinazoline compound bearing a substituted thiazoline side chain), which is a clinical candidate for the treatment of acute myeloid leukemia and solid tumors, is reported. The previously reported medicinal chemistry synthetic route A with seven steps had encountered several issues during scale-up syntheses such as low yields (7.7% overall yield), the formation of inseparable impurities, particularly in the chlorination step, use of hazardous reagents (NaH/DMF), and laborious column chromatography steps for the purification of the products. A step-by-step approach to overcome the above issues was planned and implemented through two similar routes (B1 and B2) on a gram scale and finally through route B3 on a kilogram scale to synthesize 1. The final optimized synthetic route B3 does not require column chromatography purification steps. It is one step shorter than the original route A and avoided hazardous reagents for the alkylation reaction in step 2. Furthermore, the highlights of the new route B3 include liquid-liquid continuous extraction of compound 13 in step 2, the use of POCl3 instead of SOCl2 to minimize the formation of impurities in the chlorination step 3, and telescoped synthesis of key Boc-protected amino intermediate 15 from 13, in high purity. Using the scale-up route B3, the final product 1 (3.09 kg, yield of 16.5% over six steps with an HPLC purity of 97.8%) was obtained in a single batch for preclinical testing and facilitated clinical testing of 1, which is underway.

Design, synthesis, and evaluation of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides as antitumor agents

In our continuing search for novel small-molecule anticancer agents, we designed and synthesized a series of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5), focusing on the modification of substitution in the quinazolin-4(3H)-one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5l displayed cytotoxicity up to 213-fold more potent than 5-fluorouracil and 87-fold more potent than PAC-1, the first procaspase-activating compound. Structure–activity relationship analysis revealed that substitution of either electron-withdrawing or electron-releasing groups at positions 6 or 7 on the quinazolin-4(3H)-4-one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound 5l was found to activate the caspase activity by 291% in comparison to PAC-1, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase-3 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for 5l provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent.

Design, synthesis and biological evaluation of new bivalent quinazoline analogues as IAP antagonists

We recently reported the biological evaluations of monovalent IAP antagonist 7 with good potency (MDA-MB-231, IC50 = 19 nM). In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized bivalent analogues based on quinazoline structure of 7. Optimization of cellular potency and CYP inhibition led to the identification of 27, which showed dramatic increase of over 100-fold (IC50 = 0.14 nM) and caused substantial tumor regressions in MDA-MB-231 xenograft model. These results strongly support 27 as a promising bivalent antagonist for the development of an effective anti-tumor approaches.

Self-catalyzed phototandem perfluoroalkylation/cyclization of unactivated alkenes: Synthesis of perfluoroalkyl-substituted quinazolinones

A novel visible-light-induced radical tandem trifluoromethylation/cyclization of unactivated alkenes with sodium perfluoroalkanesulfinates (Rf = CF3, C3F7, C4F9, C6F13, C8F17) under air atmosphere has been developed. A range of quinazolinones containing unactivated alkene moiety and sodium perfluoroalkanesulfinates were compatible with this transformation, leading to a variety of perfluoroalkyl-substituted quinazoline alkaloids. Remarkably, the experiment can be carried out without any metal catalyst, strong oxidant, or external photosensitizer.

Photoinduced homolytic decarboxylative acylation/cyclization of unactivated alkenes with α-keto acid under external oxidant and photocatalyst free conditions: access to quinazolinone derivatives

A novel and green strategy for the synthesis of acylated quinazolinone derivativesviaphoto-induced decarboxylative cascade radical acylation/cyclization of quinazolinone bearing unactivated alkenes has been developed. The protocol provides a novel route to access acyl radicals from α-keto acids through a self-catalyzed energy transfer process. Most importantly, the reaction proceeded smoothly without any external photocatalyst, additive or oxidant, and could be easily scaled-up in flow conditions with sunlight irradiation.

Photo-Triggered Self-Induced Homolytic Dechlorinative Sulfonylation/Cyclization of Unactivated Alkenes: Synthesis of Quinazolinones Containing a Sulfonyl Group

A self-photocatalyzed sulfonylation/cyclization of quinazolinones containing unactivated alkenes with various sulfonyl chlorides was developed. The protocol provides access to sulfonyl radicals via energy transfer from the quinazolinone skeleton to the sulfonyl chloride. Notably, the transformations proceeded without any external photocatalysts, additives, or oxidants, providing an alternative method for fabricating sulfonylated compounds.