Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors

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	Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors
其他题名	Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors
	Zhao DongMei 1; Li WenYan 1; Shi YuFang 2; Xiong XuQiong 1; Song Shuai 1; Hao ChenZhou 1; Cheng MaoSheng 1; Shen JingKang 2
	2014
发表期刊	CHINESE CHEMICAL LETTERS
ISSN	1001-8417
卷号	25 期号:2 页码:299-304
摘要	Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol (HDL-C) levels and increasing low-density lipoprotein cholesterol (LDL-C) levels. Inhibition of CETP may be a new therapy for treating atherosclerosis. Herein, we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the ZINC/big-n-greasy database, leading to the identification of compound H-10 as a potential CETP inhibitor in vitro. Based on H-10, a series of 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides were designed, synthesized, and evaluated against CETP. Compound 41 was found to have the best activity, resulting in 85.0% inhibition of CETP at 10 mu mol/L. (C) 2013 Mao-Sheng Cheng and Jing-Kang Shen. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
其他摘要	Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol (HDL-C) levels and increasing low-density lipoprotein cholesterol (LDL-C) levels. Inhibition of CETP may be a new therapy for treating atherosclerosis. Herein, we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the ZINC/big-n-greasy database, leading to the identification of compound H-10 as a potential CETP inhibitor in vitro. Based on H-10, a series of 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides were designed, synthesized, and evaluated against CETP. Compound 4l was found to have the best activity, resulting in 85.0% inhibition of CETP at 10 μmol/L.
关键词	CHIRAL N,N-DISUBSTITUTED TRIFLUORO-3-AMINO-2-PROPANOLS POTENT INHIBITORS DISCOVERY TRANSPORT Cholesteryl ester transfer protein CETP inhibitors Pharmacophore Virtual screening Synthesis
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:5059654
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/148147
专题	中国科学院金属研究所
作者单位	1.中国科学院金属研究所 2.Shanghai Pharmaceut Holding Co Ltd, Cent Res Institute, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhao DongMei,Li WenYan,Shi YuFang,et al. Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors[J]. CHINESE CHEMICAL LETTERS,2014,25(2):299-304.
APA	Zhao DongMei.,Li WenYan.,Shi YuFang.,Xiong XuQiong.,Song Shuai.,...&Shen JingKang.(2014).Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors.CHINESE CHEMICAL LETTERS,25(2),299-304.
MLA	Zhao DongMei,et al."Pharmacophore-based design, synthesis, and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides as cholesteryl ester transfer protein (CETP) inhibitors".CHINESE CHEMICAL LETTERS 25.2(2014):299-304.