Sar Of 4-Hydroxypiperidine And Hydroxyalkyl Substituted Heterocycles As Novel P38 Map Kinase Inhibitors
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS(2000)
Abstract
The 4-hydroxypiyeridine 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 SE 203580, 11 did not inhibit human cytochrome P450 isoenzymes. (C) 2000 Elsevier Science Ltd. All rights reserved.
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Key words
map kinase
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