SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors

Authors
Revesz, L Di Padova, FE Buhl, T Feifel, R Gram, H Hiestand, P Manning, U Zimmerlin, AG
Citation
L. Revesz et al., SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors, BIOORG MED, 10(11), 2000, pp. 1261-1264
Citations number
18
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
11
Year of publication
2000
Pages
1261 - 1264
Database
ISI
SICI code
0960-894X(20000605)10:11<1261:SO4AHS>2.0.ZU;2-L
Abstract
The 4-hydroxypiyeridine substituent was found to confer high p38 selectivit y devoid of COX-1 affinity, when attached to a series of pyridinyl substitu ted heterocycles. Pyridinyloxazole 11 showed a promising in vivo profile wi th 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.