Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

doi:10.1016/j.ejmech.2021.113497

	Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation
	Xu, Dandan 1,3; Sun, Deqiao 2,3,4; Wang, Wei 1,3; Peng, Xia 2; Zhan, Zhengsheng 1; Ji, Yinchun 2; Shen, Yanyan 2; Geng, Meiyu 2,3,4; Ai, Jing 2,3,5; Duan, Wenhu 1,3
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2021-08-05
卷号	220 页码:18
关键词	Axl Cancer Inhibitor Pyrrolo[2,3-d]pyrimidine
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2021.113497
通讯作者	Ai, Jing(jai@simm.ac.cn) ; Duan, Wenhu(whduan@simm.ac.cn)
英文摘要	Axl has emerged as an attractive target for cancer therapy due to its strong correlation with tumor growth, metastasis, poor survival, and drug resistance. Herein, we report the design, synthesis and structure-activity relationship (SAR) investigation of a series of pyrrolo[2,3-d]pyrimidine derivatives as new Axl inhibitors. Among them, the most promising compound 13b showed high enzymatic and cellular Axl potencies. Furthermore, 13b possessed preferable pharmacokinetic properties and displayed promising therapeutic effect in BaF3/TEL-Axl xenograft tumor model. Compound 13b may serve as a lead compound for new antitumor drug discovery. (C) 2021 Elsevier Masson SAS. All rights reserved.
资助项目	National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-011-016] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; National Natural Science Foundation of China[21702220] ; National Natural Science Foundation of China[81773762] ; Youth Innovation Promotion Association CAS[2018324] ; Personalized Medicines -Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000] ; Personalized Medicines -Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020103] ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning[2020CXJQ02]
WOS关键词	RECEPTOR TYROSINE KINASE ; TO-MESENCHYMAL TRANSITION ; SMALL-MOLECULE INHIBITOR ; CELL LUNG-CANCER ; C-MET ; THERAPEUTIC TARGET ; PHASE-I ; ANTITUMOR EFFICACY ; DRUG-RESISTANCE ; TAM RECEPTORS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000659148800036
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296964]
专题	中国科学院上海药物研究所
通讯作者	Ai, Jing; Duan, Wenhu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 5.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, 1 Xiangshan Branch Lane, Hangzhou 330106, Peoples R China
推荐引用方式 GB/T 7714	Xu, Dandan,Sun, Deqiao,Wang, Wei,et al. Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,220:18.
APA	Xu, Dandan.,Sun, Deqiao.,Wang, Wei.,Peng, Xia.,Zhan, Zhengsheng.,...&Duan, Wenhu.(2021).Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,220,18.
MLA	Xu, Dandan,et al."Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 220(2021):18.