Design, synthesis and pharmacological evaluation of new acyl sulfonamides as potent and selective Bcl-2 inhibitors

doi:10.1016/j.bmc.2017.12.001

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	Design, synthesis and pharmacological evaluation of new acyl sulfonamides as potent and selective Bcl-2 inhibitors
	Liu, Xiaohua 2,3; Zhang, Yu 4; Huang, Wenjing 4; Tan, Wenfu 4; Zhang, Ao1,2,3
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2018-01-15
卷号	26 期号:2 页码:443-454
关键词	Bcl-2 Bcl-xL Sulfonamide Navitoclax Apoptosis
ISSN号	0968-0896
DOI	10.1016/j.bmc.2017.12.001
文献子类	Article
英文摘要	The antiapoptotic protein Bcl-2, overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, we report a different structural modification approach on ABT-263 by merging the piperazinyl-phenyl fragment into a bicyclic framework leading to a series of novel analogues, among which tetrahydroisoquinoline 13 was nearly equally potent against Bcl-2 as ABT-263. Further SAR in the P4-interaction pocket affored the difluoroazetidine substituted analogue 55, which retained good Bcl-2 activity with improved Bcl-2/Bcl-xL selectivity. (C) 2017 Elsevier Ltd. All rights reserved.
资助项目	Chinese NSF[81773565] ; Chinese NSF[81773767] ; Chinese NSF[81430080] ; National Program on Key Basic Research Project of China[2015CB910603-004] ; Chinese Academy of Sciences[GJHZ1622] ; Chinese Academy of Sciences[160621] ; Shanghai Commission of Science and Technology[16XD1404600] ; Shanghai Commission of Science and Technology[14431900400] ; CAS Key Laboratory of Receptor Research of SIMM[SIMM1606YKF-08] ; CAS Key Laboratory of Receptor Research of SIMM[SIMM1606YZZ-06]
WOS关键词	FAMILY ; ANTAGONISTS ; DISCOVERIES ; PROTEINS ; DOCKING
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000419073800012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272283]
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	Tan, Wenfu; Zhang, Ao
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, SIMM, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, State Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Xiaohua,Zhang, Yu,Huang, Wenjing,et al. Design, synthesis and pharmacological evaluation of new acyl sulfonamides as potent and selective Bcl-2 inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2018,26(2):443-454.
APA	Liu, Xiaohua,Zhang, Yu,Huang, Wenjing,Tan, Wenfu,&Zhang, Ao.(2018).Design, synthesis and pharmacological evaluation of new acyl sulfonamides as potent and selective Bcl-2 inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,26(2),443-454.
MLA	Liu, Xiaohua,et al."Design, synthesis and pharmacological evaluation of new acyl sulfonamides as potent and selective Bcl-2 inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 26.2(2018):443-454.