Document Detail


Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists.
MedLine Citation:
PMID:  18595693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of aniline-substituted tetrahydroquinoline C5a receptor antagonists were discovered. A functionality requirement of ortho substitution on the aniline was revealed. Secondary anilines, in general, outperformed tertiary analogs in inhibition of C5a-induced calcium mobilization. Further enhancement of activity was realized in the presence of an ortho hydroxyalkyl side chain. The functional IC(50) of selected analogs was optimized to the single-digit nanomolar level.
Authors:
Yong Gong; J Kent Barbay; Mieke Buntinx; Jian Li; Jean Van Wauwe; Concha Claes; Guy Van Lommen; Pamela J Hornby; Wei He
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Publication Detail:
Type:  Journal Article     Date:  2008-06-20
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  18     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-11-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  3852-5     Citation Subset:  IM    
Affiliation:
Johnson & Johnson Pharmaceutical Research and Development, Spring House, PA 19477-0776, USA. ygong@prdus.jnj.com
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MeSH Terms
Descriptor/Qualifier:
Aniline Compounds / chemistry*
Binding Sites
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Inhibitory Concentration 50
Ligands
Models, Chemical
Molecular Conformation
Molecular Structure
Quinolines / chemistry*
Receptor, Anaphylatoxin C5a / antagonists & inhibitors*
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Aniline Compounds; 0/Ligands; 0/Quinolines; 0/Receptor, Anaphylatoxin C5a; 62-53-3/aniline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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