1269662-90-9

Basic information

• Product Name: N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine
• Synonyms: N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine
• CAS NO: 1269662-90-9
• Molecular Weight: 332.765
• Mol File: 1269662-90-9.mol
• Article Data: 8

Chemical Properties

• CAS DataBase Reference: N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine(CAS DataBase Reference)
• NIST Chemistry Reference: N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine(1269662-90-9)
• EPA Substance Registry System: N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine(1269662-90-9)

Safety Data

• Hazardous Substances Data: 1269662-90-9(Hazardous Substances Data)

Upstream product

• 19013-10-6 ethyl 4-hydroxy-3-nitrobenzoate 
• 1222172-51-1 ethyl 5-acetamido-2-amino-4-ethoxybenzoate 
• 780821-04-7 ethyl 3-acetamido-4-ethoxybenzoate 
• 198704-99-3 ethyl 3-acetamido-4-hydroxybenzoate 
• 162012-70-6 4-chloro-7-fluoro-6-nitroquinazoline 
• 162012-69-3 7-fluoro-6-nitro-3H-quinazolin-4-one 
• 367-21-5 3-chloro-4-fluorophenylamine 
• 162012-67-1 N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 
• 89-77-0 2-Amino-4-chlorobenzoic acid 
• 1360430-70-1 N-(3-chloro-4-fluorophenyl)-7-ethoxy-6-nitroquinazoline-4-amine 
• 936954-09-5 7-ethoxy-6-nitroquinazolin-4(1H)-one 
• 53449-14-2 7-Chloro-6-nitro-quinazolin-4-one 
• 31374-18-2 7-chloroquinazolin-4(1H)-one 
• 936954-10-8 4-chloro-7-ethoxy-6-nitroquinazoline 

Downstream Products

• 1360430-60-9 N-(4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)-3-(dimethylamino)propanamide 
• 1360430-61-0 N-(4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)-3-piperidin-1-ylpropanamide 
• 1360430-62-1 N-(4-((3-chloro-4-fluorophenyl)amino)-7-ethoxyquinazolin-6-yl)-3-morpholinopropanamide 
• 1360430-59-6 N-(4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)acrylamide 
• 1360430-71-2 3-chloro-N-(4-(3-Chloro-4-fluoroanilino)-7-ethoxyquinazolin-6-yl)propanamide 

Relevant articles and documents

Synthesis, reactivity, and biological activity of gold(i) complexes modified with thiourea-functionalized tyrosine kinase inhibitors

Thiourea-modified 3-chloro-4-fluoroanilino-quinazoline derivatives have been studied as potential receptor-targeted carrier ligands in linear gold(I) complexes. The molecules mimic the epidermal growth factor receptor (EGFR) tyrosine kinase-targeted inhibitor gefitinib. Thiourea groups were either directly attached to quinazoline-C6 (compounds 4, 5, and 7) or linked to this position via a flexible ethylamino chain (compound 9). Compound 7 acts as a thiourea-S/quinazoline-N1 mixed-donor ligand, giving the unexpected dinuclear complex [{Au(μ-7-S,N)}2]X2 (X = Cl-, SCN-) (12a,b) (X-ray crystallography, electrospray mass spectrometry). Derivative 9 forms a stable linear complex, [Au(PEt3)(9-S)](NO3) (13). The biological activity of the carrier ligands and corresponding gold(I) complexes was studied in NCI-H460 and NCI-H1975 lung cancer cells. Compound 9 partially overcomes resistance to gefitinib in NCI-H1975, a lung cancer cell line characterized by a L858R/T790M mutation in EGFR (IC50 values of 1.7 and 30 μM, respectively). The corresponding gold complex (13) maintains activity in the low-micromolar concentration range similar to the metal-free carrier. Compound 9 and the corresponding [Au(PEt3)] complex, 13, inhibit EGFR kinase-mediated phosphorylation with sub-micromolar IC50 values similar to those observed for gefitinib under the same assay conditions. Potential mechanisms of action and reactions in biological media of this new type of hybrid agent, as well as shortcomings of the current design are discussed.

Balancing reactivity and antitumor activity: heteroarylthioacetamide derivatives as potent and time-dependent inhibitors of EGFR

Second- and third-generation inhibitors of EGFR possess an acrylamide group which alkylates Cys797, allowing to overcome resistance due to insurgence of T790M mutation. Less reactive warheads, yet capable to bind the target cysteine, may be useful to design newer and safer inhibitors. In the present work, we synthesized a 2-chloro-N-(4-(phenylamino)quinazolin-6-yl)acetamide (8) derivative as a prototype of EGFR inhibitor potentially able to react with Cys797 by nucleophilic substitution. We then tuned the reactivity of the acetamide fragment by replacing the chlorine leaving group with (hetero)-aromatic thiols or carboxylate esters. Among the synthesized derivatives, the 2-((1H-imidazol-2-yl)thio)acetamide 16, while showing negligible reactivity with cysteine in solution, caused long-lasting inhibition of wild-type EGFR autophosphorylation in A549 cells, resulted able to bind recombinant EGFR L858R/T790M in a time-dependent manner, and inhibited both EGFR autophosphorylation and proliferation in gefitinib-resistant H1975 lung cancer cells (expressing EGFR L858R/T790M mutant) at low micromolar concentration.

Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors

We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies.