Details

Autor(en) / Beteiligte

• Cee, Victor J
• Frohn, Mike
• Lanman, Brian A
• Golden, Jennifer
• Muller, Kristine
• Neira, Susana
• Pickrell, Alex
• Arnett, Heather
• Buys, Janet
• Gore, Anu
• Fiorino, Mike
• Horner, Michelle
• Itano, Andrea
• Lee, Matt R
• McElvain, Michele
• Middleton, Scot
• Schrag, Michael
• Rivenzon-Segal, Dalia
• Vargas, Hugo M
• Xu, Han
• Xu, Yang
• Zhang, Xuxia
• Siu, Jerry
• Wong, Min
• Bürli, Roland W

Titel

Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P1 and S1P5

Ist Teil von

• ACS medicinal chemistry letters, 2011-02, Vol.2 (2), p.107-112

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2011

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• The optimization of a series of thiazolopyridine S1P1 agonists with limited activity at the S1P3 receptor is reported. These efforts resulted in the discovery of 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo-[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid (5d, AMG 369), a potent dual S1P1/S1P5 agonist with limited activity at S1P3 and no activity at S1P2/S1P4. Dosed orally at 0.1 mg/kg, 5d is shown to reduce blood lymphocyte counts 24 h postdose and delay the onset and reduce the severity of experimental autoimmune encephalomyelitis in rat.