267243-68-5

Usage

Uses

Used in Pharmaceutical Industry:
N4-(3-chloro-4-fluorophenyl)-7-(3-Morpholinopropoxy)quinazoline-4,6-diaMine is used as a drug candidate for the development of novel therapeutic agents. Its ability to inhibit certain enzymes and receptors makes it a valuable asset in the discovery and design of new drugs for the treatment of various diseases and conditions.
Used in Medicinal Chemistry Research:
N4-(3-chloro-4-fluorophenyl)-7-(3-Morpholinopropoxy)quinazoline-4,6-diaMine serves as a key compound in medicinal chemistry research, where its unique structure and properties are investigated for potential applications in drug discovery. Researchers explore its interactions with biological targets and evaluate its efficacy and safety in preclinical studies to advance the development of new pharmaceuticals.
Used in Drug Design and Optimization:
N4-(3-chloro-4-fluorophenyl)-7-(3-Morpholinopropoxy)quinazoline-4,6-diaMine is utilized in the process of drug design and optimization, where its chemical structure is modified and fine-tuned to enhance its pharmacological properties, selectivity, and potency. This process involves the synthesis of analogs and derivatives to identify the most effective and safe compounds for further development as drug candidates.

Upstream product

• 4441-30-9 3-morpholin-4-ylpropan-1-ol 
• 367-21-5 3-chloro-4-fluorophenylamine 
• 865-47-4 potassium tert-butylate 
• 162012-69-3 7-fluoro-6-nitro-3H-quinazolin-4-one 
• 446-32-2 4-fluoroanthranilic acid 
• 125422-83-5 4 (3-bromopropyl)-morpholine 
• 16499-57-3 7-fluoro-3H-quinazolin-4-one 
• 162012-67-1 N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 
• 162012-70-6 4-chloro-7-fluoro-6-nitroquinazoline 
• 267243-64-1 (3-chloro-4-fluorophenyl)-[7-(3-morpholino-4-yl-propoxy)-6-nitroquinazolin-4-yl]-amine 

Downstream Products

• 267243-28-7 canertinib 
• 267243-64-1 (3-chloro-4-fluorophenyl)-[7-(3-morpholino-4-yl-propoxy)-6-nitroquinazolin-4-yl]-amine 

Relevant academic research and scientific papers

Quinazoline derivative, preparation method and pharmaceutical application thereof

The invention discloses a quinazoline derivative, a preparation method and pharmaceutical application thereof. The invention provides the quinazoline derivative which is a compound shown as formula Iin the specification, and also provides a pharmaceutical

Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors

A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC50 = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study. The overall attractive profile of 6g made it an interesting compound for further development.

6-Oxooxazolidine–quinazolines as noncovalent inhibitors with the potential to target mutant forms of EGFR

Despite the remarkable benefits of gefitinib, the clinical efficacy is eventually diminished due to the acquired point mutations in the EGFR (T790M). To address this unmet medical need, we demonstrated a strategy to prepare a hybrid analogue consisting of the oxooxazolidine ring and the quinazoline scaffold and provided alternative noncovalent inhibitors targeting mutant forms of EGFR. Most of the derivatives displayed moderate to good anti-proliferative activity against gefitinib-resistant NCI-H1975. Some of them exhibited potent EGFR kinase inhibitory activities, especially on EGFRT790Mand EGFRL858Rkinases. SAR studies led to the identification of a hit 9a that can target both of the most common EGFR mutants: L858R and T790M. Also, 9a displayed weaker inhibitory against cancer cell lines with low level of EGFR expression and good chemical stability under different pH conditions. The work presented herein showed the potential for developing noncovalent inhibitors targeting EGFR mutants.

QUINAZOLINE DERIVATIVE, PREPARATION METHOD THEREFOR, INTERMEDIATE, COMPOSITION AND APPLICATION THEREOF

Disclosed are as represented by Formula (I) a quinazoline derivative and a pharmaceutical acceptable salt thereof, or, an enantiomer, a non-enantiomer, a tautomer, a racemate, a solvate, a metabolic precursor, or a prodrug of both. Also disclosed are a pr

Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase

Irreversible HER/erbB inhibitors selectively inhibit HER-family kinases by targeting a unique cysteine residue located within the ATP-binding pocket. Sequence alignment reveals that this rare cysteine is also present in ten other protein kinases including all five Tec-family members. We demonstrate that the Tec-family kinase Bmx is potently inhibited by irreversible modification at Cys496 by clinical stage EGFR inhibitors such as CI-1033. This cross-reactivity may have significant clinical implications.

Method for the simplified production of (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-nitro-quinazoline-4-yl]-amine or (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-amino-quinazoline-4-yl]-amine

The invention concerns a one-pot reaction for the preparation of (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-nitroquinazolin-4-yl]-amine (I) or of (3-chloro-4-fluorophenyl)-[7-(3-morpholino-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)

METHOD FOR THE SIMPLIFIED PRODUCTION OF (3-CHLORO-4-FLOUROPHENYL)-[7-(3-MORPHOLIN-4-YL-PROPOXY)-6-NITRO-QUINAZOLINE-4YL]-AMINE OR (3-CHLORO-4-FLUOROPHENYL)-[7-(3-MORPHOLIN-4-YL-PROPOXY)-6-AMINO-QUINAZOLINE-4-YL]-AMINE

The invention concerns a one-pot reaction for the preparation of (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-nitroquinazolin-4-yl]-amine (I) or of (3-chloro-4-fluorophenyl)-[7-(3-morpholino-4-yl-propoxy)-6-aminoquinazolin-4-yl]-amine (VII)

Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4- (phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions

4-Anilinoquinazoline- and 4-anilinopyrido[3,2-d]pyrimidine-6-acrylamides substituted with solubilizing 7-alkylamine or 7-alkoxyamine side chains were prepared by reaction of the corresponding 6-amines with acrylic acid or acrylic acid anhydrides. In the pyrido[3,2-d]pyrimidine series, the intermediate 6-amino-7-alkylamines were prepared from 7-bromo-6- fluoropyrido[3,2-d]pyrimidine via Stille coupling with the appropriate stannane under palladium-(0) catalysis. This proved a versatile method for the introduction of cationic solubilizing side chains. The compounds were evaluated for their inhibition of phosphorylation of the isolated EGFR enzyme and for inhibition of EGF-stimulated autophosphorylation of EGFR in A431 cells and of heregulin-stimulated autophosphorylation of erbB2 in MDA-MB 453 cells. Quinazoline analogues with 7-alkoxyamine solubilizing groups were potent irreversible inhibitors of the isolated EGFR enzyme, with IC50([app]) values from 2 to 4 nM, and potently inhibited both EGFR and erbB2 autophosphorylation in cells. 7-Alkylamino- and 7- alkoxyaminopyrido[3,2-d]pyrimidines were also irreversible inhibitors with equal or superior potency against the isolated enzyme but were less effective in the cellular autophosphorylation assays. Both quinazoline- and pyrido[3,2- d]pyrimidine-6-acrylamides bound at the ATP site alkylating cysteine 773, as shown by electrospray ionization mass spectrometry, and had similar rates of absorptive and secretory transport in Caco-2 cells. A comparison of two 7- propoxymorpholide analogues showed that the pyrido[3,2-d]pyrimidine-6- acrylamide had greater amide instability and higher acrylamide reactivity, being converted to glutathione adducts in cells more rapidly than the corresponding quinazoline. This difference may contribute to the observed lower cellular potency of the pyrido[3,2-d]pyrimidine-6-acrylamides. Selected compounds showed high in vivo activity against A431 xenografts on oral dosing, with the quinazolines being superior to the pyrido[3,2-d]pyrimidines. Overall, the quinazolines proved superior to previous analogues in terms of aqueous solubility, potency, and in vivo antitumor activity, and one example (CI 1033) has been selected for clinical evaluation.