Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction

doi:10.1002/ardp.201900376

	Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction
	Xiao, Donghuai 1; Wang, Yu-jie 5; Wang, Han-lin 2,3,5; Zhou, Yu-bo 5; Li, Jia 2,3,4,5; Lu, Wei 1; Jin, Jiyu 1
刊名	ARCHIV DER PHARMAZIE
	2020-04-28
页码	10
关键词	antitumor arylboronic acid lenalidomide Suzuki cross-coupling
ISSN号	0365-6233
DOI	10.1002/ardp.201900376
通讯作者	Li, Jia(jli@simm.ac.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn) ; Jin, Jiyu(jyjin@chem.ecnu.edu.cn)
英文摘要	Lenalidomide is a cereblon modulator known for its antitumor, anti-inflammatory, and immunomodulatory properties in clinical applications. Recently, some reported lenalidomide analogs could exhibit a significant bioactivity through various modifications in the isoindolinone ring. In this study, we designed and synthesized a series of novel lenalidomide analogs on the basis of the installation of a methylene chain at the C-4 position of isoindolinone via the Suzuki cross-coupling reaction. These new compounds were further evaluated for their in vitro antiproliferative activities against two tumor cell lines (MM.1S and Mino). Specifically, compound 4c displayed the strongest antiproliferative activity against the MM.1S (IC50 = 0.27 +/- 0.03 mu M) and Mino (IC50 = 5.65 +/- 0.58 mu M) tumor cell lines. In summary, we have developed a new synthetic strategy for C-4 derivatization of lenalidomide, providing a bioactive scaffold that could be used to discover further potential antitumor lead compounds in pharmaceutical research.
资助项目	National Natural Science Foundation of China[81125023] ; Shanghai Science and Technology Council[16DZ2280100]
WOS关键词	THALIDOMIDE ANALOGS ; POTENT INHIBITORS ; CEREBLON ; DEGRADATION ; DEXAMETHASONE ; MODULATION ; ACTIVATION ; EFFICACY ; THERAPY ; TARGET
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000528856700001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280490]
专题	中国科学院上海药物研究所
通讯作者	Li, Jia; Lu, Wei; Jin, Jiyu
作者单位	1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod Qingdao, Qingdao, Peoples R China 5.Chinese Acad Sci, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Xiao, Donghuai,Wang, Yu-jie,Wang, Han-lin,et al. Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction[J]. ARCHIV DER PHARMAZIE,2020:10.
APA	Xiao, Donghuai.,Wang, Yu-jie.,Wang, Han-lin.,Zhou, Yu-bo.,Li, Jia.,...&Jin, Jiyu.(2020).Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction.ARCHIV DER PHARMAZIE,10.
MLA	Xiao, Donghuai,et al."Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction".ARCHIV DER PHARMAZIE (2020):10.