Discovery of novel FMS kinase inhibitors as anti-inflammatory agents.
The optimization of the arylamide lead 2 resulted in identification of a highly potent series of 2,4-disubstituted arylamides. Compound 8 (FMS kinase IC(50)=0.0008 microM) served as a proof-of-concept candidate in a collagen-induced model of arthritis in mice.
Illig
Carl R
CR
Johnson & Johnson Pharmaceutical Research & Development, Welsh & McKean Roads, Spring House, PA 19477, USA.
Chen
Jinsheng
J
Wall
Mark J
MJ
Wilson
Kenneth J
KJ
Ballentine
Shelley K
SK
Rudolph
M Jonathan
MJ
DesJarlais
Renee L
RL
Chen
Yanmin
Y
Schubert
Carsten
C
Petrounia
Ioanna
I
Crysler
Carl S
CS
Molloy
Christopher J
CJ
Chaikin
Margery A
MA
Manthey
Carl L
CL
Player
Mark R
MR
Tomczuk
Bruce E
BE
Meegalla
Sanath K
SK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D003094:Collagen; D016186:Receptor, Macrophage Colony-Stimulating Factor