Details

Autor(en) / Beteiligte

• Revesz, Laszlo
• Blum, Ernst
• Di Padova, Franco E.
• Buhl, Thomas
• Feifel, Roland
• Gram, Hermann
• Hiestand, Peter
• Manning, Ute
• Rucklin, Gerard

Titel

Novel p38 inhibitors with potent oral efficacy in several models of rheumatoid arthritis

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2004-07, Vol.14 (13), p.3595-3599

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2004

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• A pilot library of trisubstituted oxazoles, thiazoles, imidazoles (1,2,4- and 2,4,5-substituted) and imidazo[1,2- b]pyridines was prepared and evaluated in vitro and in vivo as p38α inhibitors. Four structures–– 32, 37, 45 and 59––were identified as potent inhibitors of p38α with high oral efficacy in three models of rheumatoid arthritis. A library of trisubstituted oxazoles, thiazoles, imidazoles (1,2,4- and 2,4,5-substituted) and imidazo[1,2- b]pyridines was prepared and evaluated in vitro as p38α inhibitors and in vivo in several models of rheumatoid arthritis. Four structures–– 32, 37, 45 and 59––were identified as potent inhibitors of p38α with high efficacy in the LPS induced TNFα release model in the mouse, the adjuvant induced arthritis and the collagen induced arthritis in the rat with ED 50s between 1.0 and 9.5 mg/kg p.o.