title: SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors.
abstract: The 4-hydroxypiperidine substituent was found to confer high p38 selectivity devoid of COX-1 affinity, when attached to a series of pyridinyl substituted heterocycles. Pyridinyloxazole 11 showed a promising in vivo profile with bioavailability of 64% and ED50 in rat collagen induced arthritis of 10 mg/kg po bid. In contrast to pyridinylimidazoles such as SB 203580, 11 did not inhibit human cytochrome P450 isoenzymes.
authors.affiliation: Arthritis and Bone Research, Novartis Pharma AG, Switzerland. laszlo.revesz@pharma.novartis.com
authors.forename: L
authors.initials: L
authors.lastname: Revesz
authors.forename: F E
authors.initials: FE
authors.lastname: Di Padova
authors.forename: T
authors.initials: T
authors.lastname: Buhl
authors.forename: R
authors.initials: R
authors.lastname: Feifel
authors.forename: H
authors.initials: H
authors.lastname: Gram
authors.forename: P
authors.initials: P
authors.lastname: Hiestand
authors.forename: U
authors.initials: U
authors.lastname: Manning
authors.forename: A G
authors.initials: AG
authors.lastname: Zimmerlin
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007093:Imidazoles; D010880:Piperidines; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580