Pyrroles and other heterocycles as inhibitors of p38 kinase.
Investigation of furans, pyrroles and pyrazolones identified 3-pyridyl-2,5-diaryl-pyrroles as potent, orally bioavailable inhibitors of p38 kinase. 3-(4-pyridyl-2-(4-fluoro-phenyl)-5-(4-methylsulfinylphenyl)-pyrrol e (L-167307) reduces secondary paw swelling in the rat adjuvant arthritis model: ID50 = 7.4 mg/kg/b.i.d.
de Laszlo
S E
SE
Department of Medicinal Chemistry, Merck Research Laboratory, Rahway, NJ 07065, USA.
Visco
D
D
Agarwal
L
L
Chang
L
L
Chin
J
J
Croft
G
G
Forsyth
A
A
Fletcher
D
D
Frantz
B
B
Hacker
C
C
Hanlon
W
W
Harper
C
C
Kostura
M
M
Li
B
B
Luell
S
S
MacCoss
M
M
Mantlo
N
N
O'Neill
E A
EA
Orevillo
C
C
Pang
M
M
Parsons
J
J
Rolando
A
A
Sahly
Y
Y
Sidler
K
K
O'Keefe
S J
SJ
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D011720:Pyrazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005663:Furans; D011720:Pyrazoles; D011758:Pyrroles; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases