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

页码：265 / 270

页数：6

共 22 条

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