title: Pyrroles and other heterocycles as inhibitors of p38 kinase.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratory, Rahway, NJ 07065, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: de Laszlo
authors.forename: D
authors.initials: D
authors.lastname: Visco
authors.forename: L
authors.initials: L
authors.lastname: Agarwal
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Chin
authors.forename: G
authors.initials: G
authors.lastname: Croft
authors.forename: A
authors.initials: A
authors.lastname: Forsyth
authors.forename: D
authors.initials: D
authors.lastname: Fletcher
authors.forename: B
authors.initials: B
authors.lastname: Frantz
authors.forename: C
authors.initials: C
authors.lastname: Hacker
authors.forename: W
authors.initials: W
authors.lastname: Hanlon
authors.forename: C
authors.initials: C
authors.lastname: Harper
authors.forename: M
authors.initials: M
authors.lastname: Kostura
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Luell
authors.forename: M
authors.initials: M
authors.lastname: MacCoss
authors.forename: N
authors.initials: N
authors.lastname: Mantlo
authors.forename: E A
authors.initials: EA
authors.lastname: O'Neill
authors.forename: C
authors.initials: C
authors.lastname: Orevillo
authors.forename: M
authors.initials: M
authors.lastname: Pang
authors.forename: J
authors.initials: J
authors.lastname: Parsons
authors.forename: A
authors.initials: A
authors.lastname: Rolando
authors.forename: Y
authors.initials: Y
authors.lastname: Sahly
authors.forename: K
authors.initials: K
authors.lastname: Sidler
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Keefe
mesh_terms: 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
chemical_list: 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