Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 1: Discovery and initial structure-activity relationships for 1-amino-2-phenyl-4-(piperidin-1-yl)butanes

被引：88

作者：

Dorn, CP

Finke, PE

Oates, B

Budhu, RJ

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)00637-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Screening of the Merck sample collection for compounds with CCR5 receptor binding afforded (2S)-2-(3,4-dichlorophenyl)- 1-[N-(methyl)-N-(phenylsulfonyl)amino]-4,4'-piperidin-1'-yl)]butane S-oxide (4) as a potent lead structure having an IC50 binding affinity of 35 nM. Herein, we describe the discovery of this lead structure and our initial structure-activity relationship studies directed toward the requirement for and optimization of the 1-amino fragment. (C) 2001 Published by Elsevier Science Ltd.

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页码：259 / 264

页数：6

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