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.
Eli Lilly and Co., Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. mader_mary@lilly.com
Mary
M
Mader
Alfonso
A
de Dios
Chuan
C
Shih
Rosanne
R
Bonjouklian
Tiechao
T
Li
Wesley
W
White
Beatriz
B
López de Uralde
Concepción
C
Sánchez-Martinez
Miriam
M
del Prado
Carlos
C
Jaramillo
Eugenio
E
de Diego
Luisa M
LM
Martín Cabrejas
Carmen
C
Dominguez
Carlos
C
Montero
Timothy
T
Shepherd
Robert
R
Dally
John E
JE
Toth
Arindam
A
Chatterjee
Sehila
S
Pleite
Jaime
J
Blanco-Urgoiti
Leticia
L
Perez
Mario
M
Barberis
María José
MJ
Lorite
Enrique
E
Jambrina
C Richard
CR
Nevill
Paul A
PA
Lee
Richard C
RC
Schultz
Jeffrey A
JA
Wolos
Li C
LC
Li
Robert M
RM
Campbell
Bryan D
BD
Anderson
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