Discovery and Development of Thiazolo[3,2-a]pyrimidinone Derivatives as General Inhibitors of Bcl-2 Family Proteins

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	Discovery and Development of Thiazolo[3,2-a]pyrimidinone Derivatives as General Inhibitors of Bcl-2 Family Proteins
	Zhou BC(周炳城) ; Li X(李勋) ; Li Y(李嫣) ; Xu YC(许耀春) ; Zhang ZX(张征西) ; Zhou M(周蜜) ; Zhang XL(张兴龙) ; Liu Z(刘真) ; Zhou JH(周佳海) ; Cao CY(曹春阳) ; Yu B(俞飚) ; Wang RX(王任小)
刊名	ChemMedChem
	2011
卷号	6 期号:5 页码:904-921
ISSN号	1860-7179
其他题名	噻唑并(3,2-α)嘧啶酮作为Bcl-2家族蛋白通用抑制剂的发现和发展
通讯作者	俞飚 ; 王任小
英文摘要	A class of compounds with a common thiazolo[3,2-a]pyrimidinone motif has been developed as general inhibitors of Bcl-2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization-based competitive binding assay. Its binding to the Bcl-x(L) protein was further confirmed by (15)N-HSQC NMR experiments. Structural modifications on the lead compound were guided by the outcomes of molecular modeling studies. Among the 42 compounds obtained, a number of them exhibited much improved binding affinities to Bcl-2 family proteins as compared to the lead compound. The most potent compound, BCL-LZH-40, inhibited the binding of BH3 peptides to Bcl-x(L), Bcl-2, and Mcl-1 with inhibition constants (K(i)) of 17, 534, and 200 nm, respectively.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1002/cmdc.201000484
语种	英语
WOS记录号	WOS:000289860900019
公开日期	2013-02-25
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/19141]
专题	上海有机化学研究所_生命有机化学国家重点实验室
推荐引用方式 GB/T 7714	Zhou BC,Li X,Li Y,et al. Discovery and Development of Thiazolo[3,2-a]pyrimidinone Derivatives as General Inhibitors of Bcl-2 Family Proteins[J]. ChemMedChem,2011,6(5):904-921.
APA	周炳城.,李勋.,李嫣.,许耀春.,张征西.,...&王任小.(2011).Discovery and Development of Thiazolo[3,2-a]pyrimidinone Derivatives as General Inhibitors of Bcl-2 Family Proteins.ChemMedChem,6(5),904-921.
MLA	周炳城,et al."Discovery and Development of Thiazolo[3,2-a]pyrimidinone Derivatives as General Inhibitors of Bcl-2 Family Proteins".ChemMedChem 6.5(2011):904-921.