228559-74-8Relevant articles and documents
Discovery of 2-(4-Chloro-3-(trifluoromethyl)phenyl)- N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)acetamide (CHMFL-KIT-64) as a Novel Orally Available Potent Inhibitor against Broad-Spectrum Mutants of c-KIT Kinase for Gastrointestinal Stromal Tumors
Liu, Qingsong,Wu, Yun,Wang, Beilei,Wang, Junjie,Qi, Shuang,Zou, Fengming,Qi, Ziping,Liu, Feiyang,Liu, Qingwang,Chen, Cheng,Hu, Chen,Hu, Zhenquan,Wang, Aoli,Wang, Li,Wang, Wenchao,Ren, Tao,Cai, Yujiao,Bai, Mingfeng,Liu, Jing
, p. 6083 - 6101 (2019/08/02)
Starting from our previously developed c-KIT kinase inhibitor CHMFL-KIT-8140, through a type II kinase inhibitor binding element hybrid design approach, we discovered a novel c-KIT kinase inhibitor compound 18 (CHMFL-KIT-64), which is potent against c-KIT wt and a broad spectrum of drug-resistant mutants with improved bioavailability. 18 exhibits single-digit nM potency against c-KIT kinase and c-KIT T670I mutants in the biochemical assay and displays great potencies against most of the gain-of-function mutations in the juxtamembrane domain, drug-resistant mutations in the ATP binding pocket (except V654A), and activation loops (except D816V). In addition, 18 exhibits a good in vivo pharmacokinetic (PK) profile in different species including mice, rats, and dogs. It also displays good in vivo antitumor efficacy in the c-KIT T670I, D820G, and Y823D mutant-mediated mice models as well as in the c-KIT wt patient primary cells which are known to be imatinib-resistant. The potent activity against a broad spectrum of clinically important c-KIT mutants combining the good in vivo PK/pharmacodynamic properties of 18 indicates that it might be a new potential therapeutic candidate for gastrointestinal stromal tumors.
Tyrosine kinase inhibitor and application thereof
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Paragraph 0038; 0039, (2018/09/08)
The invention discloses a tyrosine kinase inhibitor. A chemical name of the tyrosine kinase inhibitor is 1-(2-chloro-4-((6,7-dimethoxyquinoline-4-yl)oxy)phenyl)-3-(4-fluorophenyl)carbamide and a structure is shown as a formula (I). Meanwhile, the inventio
URACIL DERIVATIVES AS AXL AND C-MET KINASE INHIBITORS
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Page/Page column 89, (2013/06/05)
The present invention provides compounds of Formula I, or pharmaceutically acceptable salt forms thereof, wherein Ra, Rb, Rc, Rd, D, W, R1a, R1b, R1c,Y, R3, X, E and G are as defined herein, methods of treatment and uses thereof.
