Discovery of a novel series of cyclic urea as potent CCR5 antagonists

A novel series of cyclic urea-based CCR5 antagonists was designed aiming to resolve instability issue in the fasted simulated intestinal fluid (FSIF) associated with the acyclic urea moiety in 1. This class of CCR5 compounds demonstrated high antiviral activities against HIV-1 infection in both HOS...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-11, Vol.21 (21), p.6381-6385
Main Authors: Duan, Maosheng, Kazmierski, Wieslaw M., Tallant, Matt, Jun, Jung Ho, Edelstein, Mark, Ferris, Rob, Todd, Dan, Wheelan, Pat, Xiong, Zhiping
Format: Article
Language:English
Subjects:
Antagonist
antagonists
Anti-HIV Agents - chemistry
Anti-HIV Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
antiviral properties
Biological and medical sciences
CCR5
CCR5 Receptor Antagonists
chemistry
Chemokine
Cyclic urea
Drug Discovery
HIV infections
HIV-1
HIV-1 - drug effects
Human immunodeficiency virus 1
Medical sciences
Pharmacokinetics
Pharmacology. Drug treatments
urea
Urea - chemistry
Urea - pharmacology
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Summary:A novel series of cyclic urea-based CCR5 antagonists was designed aiming to resolve instability issue in the fasted simulated intestinal fluid (FSIF) associated with the acyclic urea moiety in 1. This class of CCR5 compounds demonstrated high antiviral activities against HIV-1 infection in both HOS and PBL assays. Further evaluation of these compounds indicated that 16- R not only substantially enhanced its stability, but also exhibited excellent pharmacokinetics properties.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2011.08.096