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Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-l-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors

文献类型：期刊论文

作者Wei, Manman2,4,5; Peng, Xia2,3; Xing, Li4,5; Dai, Yang2,3; Huang, Ruimin1,2; Geng, Meiyu2,3; Zhang, Ao1,2,4,5; Ai, Jing2,3; Song, Zilan, I2,4,5
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2018-06-25
卷号154页码:9-28
关键词FGFR VEGFR Synergistic effect Tumor growth inhibition Lucitanib
ISSN号0223-5234
DOI10.1016/j.ejmech.2018.05.005
文献子类Article
英文摘要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. (C) 2018 Elsevier Masson SAS. All rights reserved.
WOS关键词TYROSINE KINASE ; BREAST-CANCER ; SELECTIVE INHIBITOR ; THERAPEUTIC TARGET ; PANCREATIC-CANCER ; SOLID TUMORS ; METASTASIS ; AMPLIFICATION ; ANGIOGENESIS ; DISCOVERY
资助项目National Natural Science Foundation of China[81703327] ; National Natural Science Foundation of China[81773565] ; National Natural Science Foundation of China[81430080] ; National Natural Science Foundation of China[81773762] ; International Cooperative Program of the Chinese Academy of Sciences[GJHZ1622] ; Key Program of the Frontier Science of the Chinese Academy of Sciences[160621] ; Shanghai Commission of Science and Technology[16XD1404600] ; Shanghai Commission of Science and Technology[14431900400] ; "Personalized Medicines - Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000437551600002
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/279697]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物化学研究室
通讯作者Ai, Jing; Song, Zilan, I
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China;
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
3.Chinese Acad Sci, SIMM, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;
4.Chinese Acad Sci, SIMM, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
5.Chinese Acad Sci, SIMM, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Wei, Manman,Peng, Xia,Xing, Li,et al. Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-l-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,154:9-28.
APA Wei, Manman.,Peng, Xia.,Xing, Li.,Dai, Yang.,Huang, Ruimin.,...&Song, Zilan, I.(2018).Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-l-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,154,9-28.
MLA Wei, Manman,et al."Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-l-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 154(2018):9-28.

入库方式： OAI收割

来源：上海药物研究所

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