1262849-76-2

Upstream product

• 28144-70-9 anthranilic acid amide 
• 25016-01-7 5-bromo-2-methoxybenzaldehyde 
• 2476-35-9 5-bromo-2-methoxybenzoic acid 
• 62910-63-8 5-bromo-2-methoxybenzoyl chloride 
• 461422-05-9 C₁₅H₁₁BrN₂O₂ 
• 1262849-75-1 2-(5-bromo-2-methoxyphenyl)-4-hydroxyquinazoline 

Downstream Products

• 421581-49-9 4-bromo-2-(4-chloroquinazolin-2-yl)phenol 
• 1146162-26-6 (S)-tert-butyl 3-(2-(5-bromo-2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate 
• 1146162-65-3 1-tert-butyl 3-ethyl (3R,4S)-4-(2-(5-bromo-2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1,3-dicarboxylate 
• 1146162-75-5 2-(4-((3S,4R)-4-(2-hydroxypropan-2-yl)pyrrolidin-3-ylamino)quinazolin-2-yl)-4-(1H-pyrazol-3-yl)phenol 
• 1146162-51-7 (S)-4-(1H-pyrazol-4-yl)-2-(4-(pyrrolidin-3-ylamino)quinazolin-2-yl)phenol 

Relevant academic research and scientific papers

Design, Synthesis and Biological Evaluation of the Quinazoline Derivatives as L858R/T790M/C797S Triple Mutant Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Inhibition of the epidermal growth factor receptor (EGFR) has been proved to be one of the most promising strategies for the treatment of non-small cell lung cancers. A series of 2-aryl-4-amino substituted quinazoline derivatives were designed and synthesized with the purpose to overcome L858R/T790M/C797S (CTL) triple mutant drug resistance and the biological activity for inhibition of CTL kinases and EGFR wild type (WT) were evaluated. Three compounds (20, 24 and 27) showed excellent inhibitory activities against EGFR kinases triple mutant CTL (IC5050: WT/CTL >10000). Cell line evaluation showed that the most potent compound 27 was significantly potent against H1975-EGFR L858R/T790M (IC50=3.3μM) and H1975-EGFR L858R/T790M/C797S (IC50=1.2μM). Compound 27 also exhibited good microsomes stabilities in human, rat and mouse liver species, but low bioavailability. This work would be very useful for discovering new quinazoline derivatives as tyrosine kinase inhibitors targeting triple mutant L858R/T790M/C797S.

Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2

Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl)phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2-(quinazolin-2-yl) phenol 46 (IC50 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of kinases and with promising in vitro ADMET properties. Off-target activity at hERG ion channels shown by the core scaffold was successfully reduced by the addition of peripheral polar substitution. In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533).