New modifications to the area of pyrazole-naphthyl urea based p38 MAP kinase inhibitors that bind to the adenine/ATP site

Neil Moss; Steffen Breitfelder; Raj Betageri; Pier F Cirillo; Tazmeen Fadra; Eugene R Hickey; Thomas Kirrane; Rachel R Kroe; Jeffrey Madwed; Richard M Nelson; Christopher A Pargellis; Kevin C Qian; John Regan; Alan Swinamer; Carol Torcellini

doi:10.1016/j.bmcl.2007.05.042

New modifications to the area of pyrazole-naphthyl urea based p38 MAP kinase inhibitors that bind to the adenine/ATP site

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4242-7. doi: 10.1016/j.bmcl.2007.05.042. Epub 2007 May 18.

Authors

Neil Moss¹, Steffen Breitfelder, Raj Betageri, Pier F Cirillo, Tazmeen Fadra, Eugene R Hickey, Thomas Kirrane, Rachel R Kroe, Jeffrey Madwed, Richard M Nelson, Christopher A Pargellis, Kevin C Qian, John Regan, Alan Swinamer, Carol Torcellini

Affiliation

¹ Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceutical, Inc., 900 Ridgebury Road, Ridgefield, CT 0687, USA. [email protected]

PMID: 17560108
DOI: 10.1016/j.bmcl.2007.05.042

Abstract

Discovery of the pyrazole-naphthyl urea class of p38 MAP kinase inhibitors typified by the clinical candidate BIRB 796 has encouraged further exploration of this particular scaffold. Modification to the part of the inhibitor that occupies the adenine/ATP binding site has resulted in a new way to obtain potent inhibitors that possess favorable in vitro and in vivo properties.

MeSH terms

Adenine / metabolism*
Binding Sites
Humans
Models, Molecular
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / metabolism
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Protein Kinase Inhibitors
p38 Mitogen-Activated Protein Kinases
Adenine