@article{7e420ce8529b4e82a607e00b43c36249,
title = "Synthesis and structure–activity relationship studies of MI-2 analogues as MALT1 inhibitors",
abstract = "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 of ABC-DLBCL therapeutics. Due to its inherent potential cross-reactivity, further structure–activity relationship (SAR) study is imperative. In this work, five focused compound libraries based on the chemical structure of MI-2 are designed and synthesized. The systematic SARs revealed that the side chain of 2-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 terminal hydroxyl group as side chain displayed enhanced activities against MALT1. Replacement of triazole core with pyrazole is also tolerant, while structural modifications on other sites are detrimental. These findings will facilitate further development of small-molecule MALT1 inhibitors.",
keywords = "Cancer therapeutics, MALT1, MI-2 analogues, Structure–activity relationships",
author = "Guolin Wu and Haixia Wang and Wenhui Zhou and Bihua Zeng and Wenhui Mo and Kejie Zhu and Rong Liu and Jia Zhou and Ceshi Chen and Haijun Chen",
note = "Funding Information: This study was supported by grants from “Personalized Medicines–Molecular Signature-based Drug Discovery and Development”, a Strategic Priority Research Program of the Chinese Academy of Sciences ( XDA12010303 to C. Chen), the National Nature Science Foundation of China ( 81325016 and U1602221 to C. Chen, 81322038 , 81272930 and U1502222 to R. Liu, 81402781 to H. Chen), the Yunnan Applied Basic Research Key Projects ( 2015FA027 to R. Liu), the West Light Foundation of the Chinese Academy of Sciences (to R. Liu), the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to R. Liu), Scientific Research Foundation for Returned Overseas Chinese Scholars (to H. Chen). Funding Information: This study was supported by grants from ?Personalized Medicines?Molecular Signature-based Drug Discovery and Development?, a Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12010303 to C. Chen), the National Nature Science Foundation of China (81325016 and U1602221 to C. Chen, 81322038, 81272930 and U1502222 to R. Liu, 81402781 to H. Chen), the Yunnan Applied Basic Research Key Projects (2015FA027 to R. Liu), the West Light Foundation of the Chinese Academy of Sciences (to R. Liu), the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to R. Liu), Scientific Research Foundation for Returned Overseas Chinese Scholars (to H. Chen). Funding Information: This study was supported by grants from “Personalized Medicines–Molecular Signature-based Drug Discovery and Development” a Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12010303 to C. Chen), the National Nature Science Foundation of China (81325016 and U1602221 to C. Chen, 81322038, 81272930 and U1502222 to R. Liu, 81402781 to H. Chen), the Yunnan Applied Basic Research Key Projects (2015FA027 to R. Liu), the West Light Foundation of the Chinese Academy of Sciences (to R. Liu), the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to R. Liu), Scientific Research Foundation for Returned Overseas Chinese Scholars (to H. Chen). Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2018",
month = jul,
day = "23",
doi = "10.1016/j.bmc.2018.04.059",
language = "English (US)",
volume = "26",
pages = "3321--3344",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "12",
}