Antagonists of the human CCR5 receptor as anti-HIV-1 agents.: Part 2:: Structure-activity relationships for substituted 2-aryl-1-[N-(methyl)-N-(phenylsulfonyl) amino]-4-(piperidin-1-yl)butanes

被引：72
|
作者：
Finke, PE
Meurer, LC
Oates, B
Mills, SG
MacCoss, M
Malkowitz, L
Springer, MS
Daugherty, BL
Gould, SL
DeMartino, JA
Siciliano, SJ
Carella, A
Carver, G
Holmes, K
Danzeisen, R
Hazuda, D
Kessler, J
Lineberger, J
Miller, M
Schleif, WA
Emini, EA
机构：
[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA
[3] Merck Res Labs, Dept Antiviral Res, W Point, PA 19486 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 02期
关键词：
D O I：
10.1016/S0960-894X(00)00639-9
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
(2S)-2-(3,4-Dichlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (3) has been identified as a potent CCR5 antagonist lead structure having an IC50 = 35 nM. Herein, we describe the structure-activity relationship studies directed toward the requirement for and optimization of the C-2 phenyl fragment. The phenyl was found to be important for CCR5 antagonism and substitution was limited to small moieties at the 3-position (13 and 16. X=H, 3-F, 3-Cl, 3-Me). (C) 2001 Published by Elsevier Science Ltd.
引用
收藏
页码：265 / 270
页数：6
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