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

Authors
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
Citation
Pe. Finke et al., 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, BIOORG MED, 11(2), 2001, pp. 265-270
Citations number
21
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
2
Year of publication
2001
Pages
265 - 270
Database
ISI
SICI code
0960-894X(20010122)11:2<265:AOTHCR>2.0.ZU;2-M
Abstract
(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 directe d toward the requirement for and optimization of the C-2 phenyl fragment. T he phenyl was found to be important for CCR5 antagonism and substitution wa s 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.