162012-69-3

Basic information

• Product Name: 7-Fluoro-6-nitro-4-hydroxyquinazoline
• Synonyms: 4(1H)-QUINAZOLINONE, 7-FLUORO-6-NITRO-;7-FLUORO-6-NITRO-4-HYDROXY-QUINAZOLINE;7-FLUORO-6-NITRO QUINAZOLINONE;7-Fluoro-6-Nitro-4(H)-Quinazoline;6-Nitro-7-Fluoro-4-HydroxyQuinazoline;7-fluoro-6-nitroquinazolin-4(1H)-one;7-Fluoro-6-nitro-1H-quina...;7-fluoro-6-nitroquinazolin-4-ol
• CAS NO: 162012-69-3
• Molecular Formula: C₈H₄FN₃O₃
• Molecular Weight: 209.13
• EINECS: 1308068-626-2
• Product Categories: Intermediate
• Mol File: 162012-69-3.mol

Chemical Properties

• Melting Point: 282-285 °C(Solv: acetic acid (64-19-7))
• Boiling Point: 407.6 °C at 760 mmHg
• Flash Point: 200.3 °C
• Appearance: /
• Density: 1.75 g/cm³
• Vapor Pressure: 7.46E-07mmHg at 25°C
• Refractive Index: 1.713
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: -2.69±0.20(Predicted)
• CAS DataBase Reference: 7-Fluoro-6-nitro-4-hydroxyquinazoline(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Fluoro-6-nitro-4-hydroxyquinazoline(162012-69-3)
• EPA Substance Registry System: 7-Fluoro-6-nitro-4-hydroxyquinazoline(162012-69-3)

Safety Data

• Statements: 36
• Safety Statements: 26
• Hazardous Substances Data: 162012-69-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
7-Fluoro-6-nitro-4-hydroxyquinazoline is used as an intermediate in the synthesis of kinase inhibitors, specifically targeting the ATP binding site of the tyrosine kinase activity associated with the epidermal growth factor receptor (EGFR). This application is significant because the inhibition of EGFR tyrosine kinase activity has been shown to be effective in treating various types of cancer, including non-small cell lung cancer, head and neck cancer, and colorectal cancer.
The compound's role in the development of kinase inhibitors is crucial, as these inhibitors can modulate cellular signaling pathways involved in cell proliferation, differentiation, and survival. By targeting the ATP binding site, these inhibitors can disrupt the enzymatic activity of the kinase, thereby potentially slowing down or stopping the progression of cancer cells.

InChI:InChI=1/C8H4FN3O3/c9-5-2-6-4(1-7(5)12(14)15)8(13)11-3-10-6/h1-3H,(H,10,11,13)

Upstream product

• 16499-57-3 7-fluoro-3H-quinazolin-4-one 
• 1194097-41-0 2-amino-4-fluoro-5-nitrobenzoic acid 
• 77287-34-4 formamide 
• 446-32-2 4-fluoroanthranilic acid 
• 16499-57-3 7-fluoro-3,4-dihydroquinazolin-4-one 

Downstream Products

• 162012-70-6 4-chloro-7-fluoro-6-nitroquinazoline 
• 848006-02-0 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline 
• 863488-66-8 4-(3-bromophenylamino)-7-methylpiperazine-6-aminoquinazoline 
• 863488-64-6 4-(3-bromophenylamino)-7-methylpiperazine-6-nitroquinazoline 
• 863488-63-5 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-methylpiperazine-6-nitroquinazoline 
• 863488-65-7 4-(3,4-dichloro-6-fluorophenylamino)-7-methylpiperazine-6-aminoquinazoline 
• 174709-17-2 4-[(3-bromophenyl)amino]-7-fluoro-6-nitro-quinazoline 
• 724707-59-9 4-(7-fluoro-6-nitro-4-oxo-4H-quinazolin-3-ylmethyl)benzoic Acid Tert-butyl Ester 
• 267243-68-5 (3-CHLORO-4-FLUOROPHENYL)-[7-(3-MORPHOLIN-4-YL-PROPOXY)-6-AMINO-QUINAZOLINE-4-YL]-AMINE 
• 267243-64-1 (3-chloro-4-fluorophenyl)-[7-(3-morpholino-4-yl-propoxy)-6-nitroquinazolin-4-yl]-amine 
• 55496-69-0 4-chloro-7-methoxy-6-nitroquinazoline 
• 1353644-75-3 N-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-7-methoxy-6-nitroquinazolin-4-amine 
• 897025-61-5 N⁴-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-7-methoxyquinazoline-4,6-diamine 
• 1353644-76-4 C₃₀H₂₃FN₆O₃ 

Relevant articles and documents

Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing oxazole or imidazole as potential EGFR inhibitors

Six series of quinazoline derivatives bearing oxazole or imidazole (8a-f, 9a-f, 10a-d, 11a-f, 12a-d and 13a-i) were designed, synthesized and their IC50 values evaluated against three cancer cell lines (A549, MCF-7 and PC-3). Most of the thirty-five target compounds showed excellent antiproliferative activity against one or several cancer cell lines. Compound 12a showed the best activity against A549, MCF-7 and PC-3 cancer cell lines, with IC50 values of 1.90 ± 0.13 μM, 2.23 ± 0.28 μM and 2.03 ± 0.14 μM, respectively. Four selected compounds (8a, 9d, 10a and 12a) were further evaluated for the inhibitory activity against EGFR kinase. AnnexinV-FITC, propidium iodide (PI) double staining and acridine orange single staining results indicated that compound 12a could induce apoptosis of human lung cancer A549 cells.

Studying the Conformation of a Receptor Tyrosine Kinase in Solution by Inhibitor-Based Spin Labeling

The synthesis of a spin label based on PD168393, a covalent inhibitor of a major anticancer drug target, the epidermal growth factor receptor (EGFR), is reported. The label facilitates the analysis of the EGFR structure in solution by pulsed electron paramagnetic resonance (EPR) spectroscopy. For various EGFR constructs, including near-full-length EGFR, we determined defined distance distributions between the two spin labels bound to the ATP binding sites of the EGFR dimer. The distances are in excellent agreement with an asymmetric dimer of the EGFR. Based on crystal structures, this dimer had previously been proposed to reflect the active conformation of the receptor but structural data demonstrating its existence in solution have been lacking. More generally, our study provides proof-of-concept that inhibitor-based spin labeling enables the convenient introduction of site-specific spin labels into kinases for which covalent or tight-binding small-molecule modulators are available.

Structure-based virtual screening of Src kinase inhibitors

Src is an important target in multiple processes associated with tumor growth and development, including proliferation, neovascularization, and metastasis. In this study, hit identification was performed by virtual screening of commercial and in-house compound libraries. Docking studies for the hits were performed, and scoring functions were used to evaluate the docking results and to rank ligand-binding affinities. Subsequently, hit optimization for potent and selective candidate Src inhibitors was performed through focused library design and docking analyses. Consequently, we report that a novel compound '43' with an IC50 value of 89 nM, representing (S)-N-(4-(5-chlorobenzo[d][1,3]dioxol-4-ylamino)-7-(2-methoxyethoxy)quin azolin-6-yl)pyrrolidine-2-carboxamide, is highly selective for Src in comparison to EGFR (IC50 ratio > 80-fold) and VEGFR-2 (IC50 ratio > 110-fold). Compound 43 exerted anti-proliferative effects on Src-expressing PC3 human prostate cancer and A431 human epidermoid carcinoma cells, with calculated IC50 values of 1.52 and 0.78 μM, respectively. Moreover, compound 43 (0.1 μM) suppressed the phosphorylation of extracellular signal-regulated kinases and p90 ribosomal S6 kinase, downstream molecules of Src, in a time-dependent manner, in both PC3 and A431 cell lines. The docking structure of compound 43 with Src disclosed that the chlorobenzodioxole moiety and pyrrolidine ring of C-6 quinazoline appeared to fit tightly into the hydrophobic pocket of Src. Additionally, the pyrrolidine NH forms a hydrogen bond with the carboxyl group of Asp348. These results confirm the successful application of virtual screening studies in the lead discovery process, and suggest that our novel compound 43 can be an effective Src inhibitor candidate for further lead optimization.

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.

Novel protein inhibitor and preparation method and application thereof

The invention provides a novel protein inhibitor and a preparation method and application thereof, and specifically provides a compound as shown in a formula I, wherein definitions of all groups are described in the specification. The compound has good Bcl-2 family protein inhibition activity and can be used for preparing a series of medicines for treating diseases related to Bcl-2 family proteinactivity.

Afatinib refined product synthetic method

The invention discloses an afatinib refined product synthetic method, and belongs to the technical field of organic synthesis. The method particularly comprises the following steps that 4-fluoro-2-aminobenzoic acid and formamidine acetate are subjected to a ring-closure reaction to synthesize a compound of the formula I; the compound of the formula I is subjected to a nitration reaction to synthesize a compound of the formul II; the compound of the formula II and 3-chloro-4-fluoroaniline are subjected to dehydration to synthesize a compound of the formula III, the compound of the formula III and 3-hydroxy-tetrahydrofuran synthesize a compound of a formula IV through a nucleophilic substitution reaction; the compound of the formula IV is reduced to generate a compound of the formula V underthe Pd/C catalysis; the compound of the formula V and crotonic acid synthesizes a compound of the formula VI through a dehydration condensation reaction; the compound of the formula VI and dimethylamine finally synthesize the compound of the formula VII, that is to say, an afatinib refined product is obtained. According to the afatinib refined product synthetic method, the reaction process condition is mild, the corrosion risk to reaction equipment is lowered, the reaction process is simplified, operation is easy, the purity of the product is high, and the yield is increased conveniently.

STEFs: Activated Vinylogous Protein-Reactive Electrophiles

Reported here is the synthesis of a class of semi-oxamide vinylogous thioesters, designated STEFs, and the use of these agents as new electrophilic warheads. This work includes preparation of simple probes that contain this reactive motif as well as its installation on a more complex kinase inhibitor scaffold. A key aspect of STEFs is their reactivity towards both thiol and amine groups. Shown here is that amine conjugations in peptidic and proteinogenic samples can be facilitated by initial, fast conjugation to proximal thiol residues. Evidence that both the selectivity and the reactivity can be tuned by the structure of STEFs is provided, and given the unique ability of this functionality to conjugate by an addition-elimination mechanism, STEFs are electrophilic warheads that could find broad use in chemical biology.

Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers

A series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activity against EGFRWT with the IC50 value both less than 2 nM. Among the six compounds, 44 exhibited the strongest activity (0.4 nM) and potently inhibited EGFRL858R/T790M (0.1 μM). Excitingly, the most potent compound 14 showed excellent enzyme inhibitory activity with 6.3 nM and 8.4 nM for both EGFRWT and EGFRT790M/L858R. The result of AO single staining and Annexin V/PI staining showed that the compound 14 and 44 could induce remarkable apoptosis of A549 cells. The compound 14 arrested the cell cycle at the S phase and compound 44 arrested the cell cycle at the G0 phase in A549 cells. These preliminary results demonstrate that compound 14 and 44 may be promising lead compound-targeting EGFR.

A high-purity arab league law for nepal intermediate preparation method

The present invention provides a high purity arab league law for nepal preparation method of the midbody. The method comprises: the 2 - amino - 4 - fluorobenzoic acid cyclization, nitration, [...] 3, - chloro - 4 - fluoro aniline, the reaction route shown in the following chart: . The invention material price is cheap, simple operation, high purity of the product, but also easy to industrial production.

Design, synthesis and antitumor activity of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline

Background: Cancer continues to pose a great problem and burden on society despite new treatment options. While surgery, radiotherapy, and chemotherapy have led to major improvements in patient prognosis, newer treatments are needed to more effectively manage this disease in its advanced stage. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK), which is catalytically active and under tight regulatory control. Dysregulation of its activity is strongly associated with tumorigenesis and cancer patients with altered EGFR activity tend to have a more aggressive disease, associated with a poor clinical prognosis. The family of EGFR has been intensively studied due to its strong influence on the formulation and deterioration of carcinoma. Thus, it is a good strategy that design anticancer agents by inhibiting the EGFR pathway. Methods: We group to obtain the six series compounds (8a-f, 9a-f, 10a-f, 11a-f, 12a-b and 13a-d). Hence we disclosed the design, synthesis and antitumor activity of novel quinazoline analogues against EGFR overexpression cancer cells A549 (human lung cancer), HepG-2 (human liver cancer), MCF-7 (human breast cancer) and PC-3 (human prostate cancer) and as well as the inhibitory on EGFR kinase. Moreover, apoptosis by acridine orange single staining and docking studies were presented in this paper as well. Results: Six series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline (8a-f, 9a-f, 10a-f, 11a-f, 12a-b and 13a-d) were designed, synthesized and evaluated for the half maximal inhibitory concentration (IC50) values against four cancer cell lines (A549, HepG-2, MCF-7 and PC-3). Thirty target compounds showed moderate to excellent (1.49 - 50 μM) cytotoxicity activity against one or several cancer cell lines. The compound 13a showed the best activity against A549, HepG2, MCF-7 and PC-3 cancer cell lines, with the IC50 values of 1.49 ± 0.17 μM, 2.90 ± 0.24 μM, 1.85 ± 0.19 μM, 3.30 ± 0.22 μM, respectively. What’s more, the secondary amines were introduced to the target compounds to improve the water-soluble. The results showed that the compounds were beneficial to the cytotoxicity activity. Furthermore, the results prompted us that this series of compounds may be a kind of potential epidermal growth factor receptor (EGFR) kinase inhibitors. Conclusion: Six series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4tetrahydroquinoline moiety (8a-f, 9a-f, 10a-f, 11a-f, 12a-b and 13a-d) were designed, synthesized and evaluated for the IC50 values of cytotoxicity against four cancer cell lines (A549, HepG-2, MCF-7 and PC-3). Thirty synthesized compounds showed moderate to excellent cytotoxicity activity against the different cancer cells. Especially, the compound 13a exerted antitumor effects in a dosage-dependent manner and the IC50 values of compound 13a were 1.49 μM, 2.90 μM, 1.85 μM and 3.30 μM against A549, HepG-2, MCF-7 and PC-3, respectively. From the antitumor activity data show that the compounds possessed selectivity for A549 and MCF-7 cancer cell lines. It meant that the compounds had better treatment effect on lung cancer and breast cancer. On the whole, the compounds substituted by 1,2,3,4-tetrahydroquinoline at C-4 position of quinazoline and (S)-tetrahydrofuran-3-ol at C-8 position of quinazoline were beneficial to the cytotoxicity activity. From the result of acridine orange (AO) single staining which indicated the compound 13a could induce apoptosis of A549 cells. From the result of Docking Studies, we hypothesized that the C-4 position of quinazoline were substituted by 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline with the equal influence of the cytotoxicity activity. Overall, the results prompted us that this series of compounds may be a kind of potential EGFR kinase inhibitors.