1344668-98-9Relevant academic research and scientific papers
1,7-naphthyridine 1-oxides as novel potent and selective inhibitors of p38 mitogen activated protein kinase
Lumeras, Wenceslao,Vidal, Laura,Vidal, Bernat,Balagué, Cristina,Orellana, Adelina,Maldonado, M?nica,Dom?nguez, Mar?a,Segarra, V?ctor,Caturla, Francisco
, p. 7899 - 7910 (2012/01/05)
The design, synthesis, and ability to inhibit p38 MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNF production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked selectivity against other related kinases. After an extensive SAR exercise, several compounds from this series were identified as very potent p38 inhibitors. In vivo efficacy of some derivatives was demonstrated to reduce TNF levels in an acute murine model of inflammation (ED50 = 0.5 mg/kg in LPS-induced TNF production when dosed orally 1.5 h prior to LPS administration). The oral efficacy was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally (ED 50 1 mg/kg).
