Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors

doi:10.1016/j.bmc.2018.04.059

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors
	Guolin Wu 1; Haijun Chen 1; Wenhui Zhou 2,4; Bihua Zeng 1; Wenhui Mo 1; Kejie Zhu 1; Rong Liu 2; Jia Zhou 5; Ceshi Chen 2
	2018
发表期刊	Bioorganic & Medicinal Chemistry
期号	26 页码:3321–3344
摘要	Recent studies revealed that MALT1 is a promising therapeutic target for the treatment of ABC-DLBCL.Among several reported MALT1 inhibitors, MI-2 as an irreversible inhibitor represents a new class ofABC-DLBCL therapeutics. Due to its inherent potential cross-reactivity, further structure–activity rela-tionship (SAR) study is imperative. In this work, five focused compound libraries based on the chemicalstructure of MI-2 are designed and synthesized. The systematic SARs revealed that the side chain of2-methoxyethoxy has little impact on the activity and can be replaced by other functionalized groups,providing new MI-2 analogues with retained or enhanced potency. Compounds 81–83 with terminalhydroxyl group as side chain displayed enhanced activities against MALT1. Replacement of triazole corewith pyrazole is also tolerant, while structural modifications on other sites are detrimental. Thesefindings will facilitate further development of small-molecule MALT1 inhibitors.
关键词	Malt1 Mi-2 Analogues Structure–activity Relationships Cancer Therapeutics
DOI	10.1016/j.bmc.2018.04.059
语种	英语
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12355
专题	科研部门_肿瘤生物学（陈策实）
通讯作者	Ceshi Chen
作者单位	1.College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology Kunming, Yunnan 650223, China 3.University of Science and Technology of China, Hefei, Anhui 230027, China 4.Hubei Key Laboratory of Embryonic Stem Cell Research, Biomedical Research Institute, Hubei University of Medicine, Shiyan, Hubei 442000, China 5.Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA
推荐引用方式 GB/T 7714	Guolin Wu,Haijun Chen,Wenhui Zhou,等. Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors[J]. Bioorganic & Medicinal Chemistry,2018(26):3321–3344.
APA	Guolin Wu.,Haijun Chen.,Wenhui Zhou.,Bihua Zeng.,Wenhui Mo.,...&Ceshi Chen.(2018).Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors.Bioorganic & Medicinal Chemistry(26),3321–3344.
MLA	Guolin Wu,et al."Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors".Bioorganic & Medicinal Chemistry .26(2018):3321–3344.

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