Document Detail


Discovery of novel pyridyl carboxamides as potent CCR5 antagonists and optimization of their pharmacokinetic profile in rats.
MedLine Citation:
PMID:  21920742     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A novel series of pyridyl carboxamide-based CCR5 inhibitors was designed, synthesized, and demonstrated to be highly potent against HIV-1 infection in both HOS and PBL assays. Attempts to evaluate this series of compounds in a rat PK model revealed its instability in rat plasma. A hypothesis for this liability was proposed, and strategies to overcome this issue were pursued, leading to discovery of highly potent 40 and 41, which featured dramatically improved rat PK profiles.
Authors:
Maosheng Duan; Wieslaw M Kazmierski; Pek Y Chong; Felix Deanda; Mark Edelstein; Rob Ferris; Jennifer Peckham; Pat Wheelan; Zhiping Xiong; Huichang Zhang; Rena Nishizawa; Yoshikazu Takaoka
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-23
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  -     ISSN:  1464-3405     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-9-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Infectious Disease Medicine Discovery & Development, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27706, USA.
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