215656-53-4Relevant academic research and scientific papers
Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors
Wei, Manman,Peng, Xia,Xing, Li,Dai, Yang,Huang, Ruimin,Geng, Meiyu,Zhang, Ao,Ai, Jing,Song, Zilan
, p. 9 - 28 (2018/05/28)
Starting from the phase II clinical FGFR inhibitor lucitanib (2), we conducted a medicinal chemistry approach by opening the central quinoline skeleton coupled with a scaffold hopping process thus leading to a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives. Compound 25a was identified to show selective and equally high potency against FGFR1/2 and VEGFR2 with IC50 values less than 5.0 nM. Significant antiproliferative effects on both FGFR1/2 and VEGFR2 aberrant cancer cells were observed. In the SNU-16 xenograft model, compound 25a showed tumor growth inhibition rates of 25.0% and 81.0% at doses of 10 mg/kg and 50 mg/kg, respectively, with 5% and 10%body weight loss. In view of the synergistic potential of FGFs and VEGFs in tumor angiogenesis observed in preclinical studies, the FGFR/VEGFR2 dual inhibitor 25a may achieve better clinical benefits.
Antithrombotic agents
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, (2008/06/13)
The invention relates to novel compounds of formula (I), and their pharmaceutically acceptable salts, as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula (I), and the use of the compounds of formula (I) as thrombin inhibitors.
