205259-37-6

Basic information

• Product Name: 6,7-Difluoroquinazolin-4-ol
• Synonyms: 6,7-Difluoroquinazolin-4-ol;6,7-DIFLUOROQUINAZOLIN-4(3H)-ONE;6,7-Difluoro-1H-quinazolin-4-one
• CAS NO: 205259-37-6
• Molecular Formula: C₈H₄F₂N₂O
• Molecular Weight: 182.1269664
• Mol File: 205259-37-6.mol

Chemical Properties

• Melting Point: 257 °C
• Boiling Point: 309.2±52.0 °C(Predicted)
• Appearance: /
• Density: 1.55±0.1 g/cm3(Predicted)
• PKA: -0.40±0.20(Predicted)
• CAS DataBase Reference: 6,7-Difluoroquinazolin-4-ol(CAS DataBase Reference)
• NIST Chemistry Reference: 6,7-Difluoroquinazolin-4-ol(205259-37-6)
• EPA Substance Registry System: 6,7-Difluoroquinazolin-4-ol(205259-37-6)

Safety Data

• Hazardous Substances Data: 205259-37-6(Hazardous Substances Data)

Upstream product

• 83506-93-8 2-amino-4,5-difluorobenzoic acid 
• 6313-33-3 formamidine hydrochloride 
• 211374-80-0 2-amino-4,5-difluorobenzamide 
• 149-73-5 trimethyl orthoformate 
• 77287-34-4 formamide 
• 110-89-4 piperidine 
• 290-87-9 1,3,5-Triazine 
• 3473-63-0 formamidine acetic acid 
• 122-51-0 orthoformic acid triethyl ester 

Downstream Products

• 625080-60-6 4-chloro-6,7-difluoroquinazoline 
• 625080-61-7 4-benzylamino-6,7-difluoroquinazoline 
• 610798-31-7 N-(3-ethynylphenyl)-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazolin-4-amine 
• 722544-77-6 7-(benzyloxy)-6-fluoroquinazolin-4(1H)-one 

Relevant articles and documents

Enrichment of novel quinazoline derivatives with high antitumor activity in mitochondria tracked by its self-fluorescence

In novel synthetic 28 4-arylamino-6-fluoro quinazoline derivatives, compound 3a displayed the most remarkable inhibitory activities against tumor cells (IC50 values ranging between 0.71 and 2.30 μM) in vitro. Importantly, 3a obviously inhibited the proliferation and metastasis of A549 cells in a zebrafish xenograft model, while also mediated cell apoptosis and G0/G1-phase cell cycle arrest in A549 cells. Interestingly, 3a had excellent fluorescence at 439 nm (λex = 375 nm) in DMSO and at 428 nm (λex = 372 nm) in 0.5% DMSO-phosphate buffer, and the self-fluorescent characteristic revealed 3a itself accumulates in the mitochondria of A549 cells, which suggested the antitumor process of 3a may involve the mitochondrial apoptotic pathway. The hypothesis was verified by the increase of the intracellular reactive oxygen species, the decrease of mitochondrial membrane potential, the release of cytochrome C from the mitochondria into the cytoplasm, and the cascade activation of caspase-9 and caspase-3 when A549 cells were treated with 3a. This work has great implications for further development of anticancer agents that can be enriched in mitochondria and can be tracked in real-time in biological systems due to the ideal fluorescence.

Visible-Light Photosynthesis of CHF2/CClF2/CBrF2-Substituted Ring-fused Quinazolinones in Dimethyl Carbonate

With eco-friendly and sustainable CO2-derived dimethyl carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2/CClF2/CBrF2-substituted ring-fused quinazolinones.

Preparation method of erlotinib (by machine translation)

2 -4 Difluoro 5 - 2 -dihydroquinazoline -4 ketone and a chlorination reagent are subjected to a condensation reaction in a solvent system; and the obtained 5 - [(6 ethynylphenyl) amino] 7 -3 difluoro quinazoline and diethylene glycol are subjected to an etherification reaction in a base reagent and a solvent system to obtain the erlotinib diecainide obtained by carrying out a cyclization 4 - reaction -4 - in an alkali reagent and a solvent system at a high temperature and carrying 4 - out -6 a 7 - cyclization reaction 3 - in a solvent system at a high temperature and carrying out a cyclization reaction in a 4 - solvent system 3 - at a high temperature.6 7 . The impurity is less and controllable, the next reaction can be directly carried out, the operation is simplified, the good yield can be obtained in each step, the process flow is simplified, and the safety and the environment protection are guaranteed. (by machine translation)

Quinazoline derivative and application of quinazoline derivative to preparation of anti-tumor medicine

The invention discloses a quinazoline derivative and application of the quinazoline derivative to preparation of anti-tumor medicine. The chemical structure of the derivative is shown as the formula in the specification; in the formula, the R1 and the R2 respectively and independently represent hydrogen, halogen, ethynyl, propylene-1-yl or halogenated benzyloxy; R3 represents fluorine, piperazinyl, 1-methyl piperazine, morpholinyl, 1-(2-methoxy ethyl) piperazinyl, 1-(2-diethylaminoethyl) piperazinyl or 1-acryloyl piperazinyl. The compound provided by the invention has the obvious proliferation inhibition effects on human colon cancer cells, human non-small cell lung cancer cells, human skin squamous carcinoma cells and EGFR T790M/L858R double mutation containing human lung cancer cells, and can be used for preparing anti-tumor medicine.

Morpholinylquinazolines

The invention relates to compounds of the formulae (I), (II) and (III) in which R1, R2, R3, R4, Y, W1, W2, L, A, Alk, Cyc, Ar, Het1, Het2, Hal and n have the meaning indicated in claim 1, and/or physiologically acceptable salts, tautomers and stereo-isomers thereof, including mixtures thereof in all ratios. The compounds of the formula (I) can be used for the inhibition of serine/threonine protein kinases and for the sensitisation of cancer cells to anticancer agents and/or ionising radiation. The invention also relates to the use of the compounds of the formula (I) in the prophylaxis, therapy or progress control of cancer, tumours, metastases or angiogenesis disorders, in combination with radiotherapy and/or an anticancer agent. The invention furthermore relates to a process for the preparation of the compounds of the formula (I) by reaction of compounds of the formulae (II) and (III) and optionally conversion of a base or acid of the compounds of the formula (I) into one of their salts.

Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors

We have demonstrated that quinazolin-4(3H)-one, a nicotinamide (NI) mimic with PARP-1 inhibitory activity in the high micromolar range (IC50 = 5.75 μM) could be transformed into highly active derivatives with only marginal increase in molecular weight. Convenient one to two synthetic steps allowed us to explore extensive SAR at the 2-, and 5- through 8-positions of the quinazolin-4(3H)-one scaffold. Substitutions at the 2- and 8-positions were found to be most favorable for improved PARP-1 inhibition. The amino group at 8-position resulted in compound 22 with an IC50 value of 0.76 μM. Combination of the 8-amino substituent with an additional methyl substituent at the 2-position provided the most potent compound 31 [8-amino-2-methylquinazolin- 4(3H)-one, IC50 = 0.4 μM] in the present study. Compound 31 inhibited the proliferation of Brca1-deficient cells with an IC50 value of 49.0 μM and displayed >10-fold selectivity over wild type counterparts. Binding models of these derivatives within the active site of PARP-1 have further supported the SAR data and will be useful for future lead optimization efforts.

QUINAZOLINE DERIVATIVES AS RAF KINASE MODULATORS AND METHODS OF USE THEREOF

Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O)t; Ra is O or S.

COMPOUNDS USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS

The present invention relates to compounds useful as Chemokine Receptor antagonists. Compounds of general formula (I) are provided or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compounds and compositions for the inhibition of Chemokine Receptors and also for the treatment of various diseases, conditions, or disorders, including acute or chronic inflammatory disease, cancer, and osteolytic bone disorders.

ALKYLQUINOLINE AND ALKYLQUINAZOLINE KINASE MODULATORS

The invention is directed to alkylquinoline and alkylquinazoline compounds of Formula I: wherein R1, R2, R3, B, Z, G, Q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

Structure-activity relationships of 6-fluoroquinazolines: Dual-Acting compounds with inhibitory activities toward both TNF-α production and T cell proliferation

We synthesized various 6-fluoro-7-(1-piperazino)quinazolines based on the structure of 1 and evaluated their inhibitory activities toward both TNF-α production and T cell proliferation responses. Among these compounds, 7a, having the 3,4-(methylenedioxy)phenyl moiety at the C(4)-position of the quinazoline ring, showed both inhibitory activities. Furthermore, the oral treatment with 7a exhibited an anti-inflammatory effect in rats with adjuvant arthritis as well as an inhibitory activity toward LPS-induced TNF-α production.