Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties.
Herein we report investigations into the p38alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation.
Mader
Mary
M
Eli Lilly and Co., Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. mader_mary@lilly.com
de Dios
Alfonso
A
Shih
Chuan
C
Bonjouklian
Rosanne
R
Li
Tiechao
T
White
Wesley
W
López de Uralde
Beatriz
B
Sánchez-Martinez
Concepción
C
del Prado
Miriam
M
Jaramillo
Carlos
C
de Diego
Eugenio
E
Martín Cabrejas
Luisa M
LM
Dominguez
Carmen
C
Montero
Carlos
C
Shepherd
Timothy
T
Dally
Robert
R
Toth
John E
JE
Chatterjee
Arindam
A
Pleite
Sehila
S
Blanco-Urgoiti
Jaime
J
Perez
Leticia
L
Barberis
Mario
M
Lorite
María José
MJ
Jambrina
Enrique
E
Nevill
C Richard
CR
Lee
Paul A
PA
Schultz
Richard C
RC
Wolos
Jeffrey A
JA
Li
Li C
LC
Campbell
Robert M
RM
Anderson
Bryan D
BD
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D066246:ErbB Receptors; D048308:Mitogen-Activated Protein Kinase 14