286371-44-6Relevant articles and documents
Preparation method of VEGFR inhibitor tevozanib
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Paragraph 0037; 0047-0055, (2022/03/27)
The invention relates to a preparation method of a VEGFR (vascular endothelial growth factor receptor) inhibitor tevozanib. Compared with the prior art, according to the preparation method, the compound shown in the formula 1 and the compound shown in the formula 2 are selected to react, the reaction reagent compound shown in the formula 3 is prepared firstly, then the reaction reagent compound shown in the formula 3 and the hydroxyl of the compound shown in the formula 4 are subjected to the substitution reaction, the reaction site of the reaction is single, the yield is excellent, and reaction purification is convenient; the method provided by the invention has the advantages of simple operation process, low purification cost and high overall yield, and is suitable for industrial large-scale production of bulk pharmaceutical chemicals, and the process steps for synthesizing and preparing the tevozanib are simplified.
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.
Preparation method for Tivozanib
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Paragraph 0024, (2017/08/29)
The invention belongs to the technical field of the biological medicine, and particularly relates to a preparation method for Tivozanib. The preparation method comprises the following steps: firstly using N-[2-chlorine-4-hydroxy-phenyl]-N'-(5-methyl-3-isoxazolyl)-urea and 4-chlorine-6,7-dimethoxy quinolin as raw materials, reacting under the alkaline condition to obtain an intermediate product 4-[(4-amino-3-chlorophenol)-oxy]-6,7-dimethoxy quinolin, and reacting with 3-amino-5-methylisoxazole and N,N'-carbonyldiimidazole, to obtain a target product of the Tivozanib. Compared with the prior art, the preparation method has the beneficial effect. The used raw materials in the preparation process are easily obtained, the prepared Tivozanib has high purity (more than 99.65%) and the most of the contained impurities are the raw materials in the preparation process. the ingredients are clear relatively, and there are less harmful by-products.
