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

Authors
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
Citation
Cp. Dorn et al., 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, BIOORG MED, 11(2), 2001, pp. 259-264
Citations number
32
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
2
Year of publication
2001
Pages
259 - 264
Database
ISI
SICI code
0960-894X(20010122)11:2<259:AOTHCR>2.0.ZU;2-L
Abstract
Screening of the Merck sample collection for compounds with CCR5 receptor b inding afforded (2S)-2-(3,4-dichlorophenyl)- 1-[N-(methyl)-N-(phenylsulfony l)amino]-4,4'-piperidin-1'-yl)]butane S-oxide (4) as a potent lead structur e having an IC50 binding affinity of 35 nM. Herein, we describe the discove ry of this lead structure and our initial structure-activity relationship s tudies directed toward the requirement for and optimization of the 1-amino fragment. (C) 2001 Published by Elsevier Science Ltd.