New modifications to the area of pyrazole-naphthyl urea based p38 MAP kinase inhibitors that bind to the adenine/ATP site.
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.
Moss
Neil
N
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceutical, Inc., 900 Ridgebury Road, Ridgefield, CT 0687, USA. nmoss@rdg.boehringeringleheim.com
Breitfelder
Steffen
S
Betageri
Raj
R
Cirillo
Pier F
PF
Fadra
Tazmeen
T
Hickey
Eugene R
ER
Kirrane
Thomas
T
Kroe
Rachel R
RR
Madwed
Jeffrey
J
Nelson
Richard M
RM
Pargellis
Christopher A
CA
Qian
Kevin C
KC
Regan
John
J
Swinamer
Alan
A
Torcellini
Carol
C
D000225:Adenine / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; D000225:Adenine