- VINYL COMPOUNDS AS FGFR AND VEGFR INHIBITORS
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FGFR and VEGFR inhibitors are provided, and compounds represented by formula (1) or formula (II) as FGFR and VEGFR inhibitors, pharmaceutically acceptable salts or tautomers thereof are specifically disclosed.
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Paragraph 0208; 0209
(2018/06/23)
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- Discovery of 3-(5′-Substituted)-Benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors: Design, Synthesis, and Biological Evaluation
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Fibroblast growth factor receptor (FGFR) represents an attractive oncology target for cancer therapy in view of its critical role in promoting cancer formation and progression, as well as causing resistance to approved therapies. In this article, we describe the identification of the potent pan-FGFR inhibitor (R)-21c (FGFR1-4 IC50 values of 0.9, 2.0, 2.0, and 6.1 nM, respectively). Compound (R)-21c exhibited excellent in vitro inhibitory activity against a panel of FGFR-amplified cell lines. Western blot analysis demonstrated that (R)-21c suppressed FGF/FGFR and downstream signaling pathways at nanomolar concentrations. Moreover, (R)-21c provided nearly complete inhibition of tumor growth (96.9% TGI) in NCI-H1581 (FGFR1-amplified) xenograft mice model at the dose of 10 mg/kg/qd via oral administration.
- Yan, Wei,Wang, Xinyi,Dai, Yang,Zhao, Bin,Yang, Xinying,Fan, Jun,Gao, Yinglei,Meng, Fanwang,Wang, Yuming,Luo, Cheng,Ai, Jing,Geng, Meiyu,Duan, Wenhu
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p. 6690 - 6708
(2016/08/06)
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- A chiral 1 - (3,5- two chloropyridine -4-yl)-ethanol synthesis method
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The invention discloses an asymmetric synthesis method of 1-(3,5-dichloropyridine-4-yl)-ethanol. The asymmetric synthesis method comprises the following steps: (A) under an action of lithium amide, carrying out a reaction of 3,5-dichloropyridine (I) with acetaldehyde to generate (+/-)-1-(3,5-dichloropyridine-4-yl)-ethanol (II); (B) under an action of an oxidant, allowing (+/-)-1-(3,5-dichloropyridine-4-yl)-ethanol (II) to generate 1-(3,5-dichloropyridine-4-yl)-ethyl ketone (III); and (C) in the presence of a chiral ligand, carrying out a reaction of 1-(3,5-dichloropyridine-4-yl)-ethyl ketone with a borane reagent, and thus obtaining the 1-(3,5-dichloropyridine-4-yl)-ethanol (IV) having a single optical isomer. Compared with traditional chiral column separation of (+/-)-1-(3,5-dichloropyridine-4-yl)-ethanol, the method has the prominent advantages that: (1) the reactions are simple, the operation is easy, the total yield is high, and the optical purity is more than 98%; (2) the industrial preparation period is shortened obviously, and equipment requirements are low; and (3) the preparation cost is low, and the method is suitable for industrial production.
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- CRYSTALLINE (R)-(E)-2-(4-(2-(5-(1-(3,5-DICHLOROPYRIDIN-4-YL)ETHOXY)-1H-INDAZOL-3-YL)VINYL)-1H-PYRAZOL-1-YL)ETHANOL
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The present invention provides crystalline (R)-(E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol useful in the treatment of cancer.
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Page/Page column 2
(2012/04/11)
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- VINYL INDAZOLYL COMPOUNDS
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The present invention provides vinyl indazoiyl compounds useful in the treatment of cancer.
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Page/Page column 4
(2010/11/18)
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