286371-49-1Relevant articles and documents
Discovery of 1,6-naphthyridinone-based MET kinase inhibitor bearing quinoline moiety as promising antitumor drug candidate
Chen, Tao,Fang, Wei-Rong,Huang, Wei,Li, Yun-Man,Liu, Peng-Fei,Zhuo, Lin-Sheng
, (2020/02/29)
A series of 1,6-naphthyridinone-based MET kinase inhibitors bearing quinoline moiety in block A were designed and synthesized based on the structures of Cabozantinib and our reported compound IV. Extensive SAR and DMPK studies led to the identification of 20j, a potent and orally bioavailable MET kinase inhibitor with favorable kinase selectivity. More importantly, 20j exhibited statistically significant tumor growth inhibition (Tumor growth inhibition/TGI of 131%, 4/6 partial regression/PR) in the U-87 MG xeograft model, which is superior to that of Cabozantinib (TGI of 97%, 2/6 PR), and significantly better than that of compound IV (TGI of 15%, 0/6 PR) at the same dose (12.5 mg/kg). Combined with favorable in vitro potency, kinase selectivity, pharmacokinetic profile and in vivo efficacy, the promising antitumor drug candidate 20j has subsequently advanced into preclinical research.
CARBAMATE AND UREA COMPOUNDS AS MULTIKINASE INHIBITORS
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, (2019/07/13)
The present disclosure describes carbamate and urea compounds as novel multikinase inhibitors and methods for preparing them. The pharmaceutical compositions comprising such multikinase inhibitors and methods of using them for treating cancer, infectious diseases, and other disorders associated with kinases are also described.
Quinoline or quinazoline derivatives as well as preparation method and application thereof
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, (2017/04/11)
The invention relates to quinoline or quinazoline derivatives as well as a preparation method and an application thereof, namely, the quinoline or quinazoline derivatives shown as the formula I as well as pharmaceutically acceptable salts and hydrates or prodrugs of the quinoline or quinazoline derivatives. The structure is shown in the specification, wherein A1, A2, R1, R2, R3, R4, R5, R6, X, Y, Z, M, W, Cy1, Cy2, m and n are defined in the specification. The invention further relates to the function of the compounds in the general formula I for inhibiting MET kinase and the application of the compounds as well as the pharmaceutically acceptable salts and hydrates of the compounds in preparation of drugs for treating diseases caused by abnormal high expression of the MET kinase, in particular to the application in preparation of drugs for treating and preventing cancer.