Structure-based optimization of aminopyridines as PKCθ inhibitors

The identification of a novel series of PKCθ inhibitors and subsequent optimization using docking based on a crystal structure of PKCθ is described. SAR was rapidly generated around an amino pyridine-ketone hit; (6-aminopyridin-2-yl)(2-aminopyridin-3-yl)methanone 2 leading to compound 21 which signi...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 22; no. 14; pp. 4645 - 4649
Main Authors Jimenez, Juan-Miguel, Davis, Christopher, Boyall, Dean, Fraysse, Damien, Knegtel, Ronald, Settimo, Luca, Young, Stephen, Bolton, Claire, Chiu, Peter, Curnock, Adam, Rasmussen, Richele, Tanner, Adam, Ager, Ian
Format Journal Article
LanguageEnglish
Published Amsterdam Elsevier Ltd 15.07.2012
Elsevier
Subjects
Aminopyridine
Aminopyridines - chemistry
Aminopyridines - pharmacology
Animals
Biological and medical sciences
crystal structure
interleukin-2
Kinase
Medical sciences
Mice
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
PKCθ
Protein Kinase C - antagonists & inhibitors
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
SEB-IL2
Structure-Activity Relationship
T cell receptor
SEB-IL2
T cell receptor
PKCθ
Kinase
Aminopyridine
Protein kinase C
Enzyme
Transferases
T-Lymphocyte
Inhibitor
Optimization
Pyridine derivatives
Online AccessGet full text

Cover

More Information
Summary:The identification of a novel series of PKCθ inhibitors and subsequent optimization using docking based on a crystal structure of PKCθ is described. SAR was rapidly generated around an amino pyridine-ketone hit; (6-aminopyridin-2-yl)(2-aminopyridin-3-yl)methanone 2 leading to compound 21 which significantly inhibits production of IL-2 in a mouse SEB-IL2 model.
Bibliography:http://dx.doi.org/10.1016/j.bmcl.2012.05.114
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.05.114