Discovery of AMG 369, a thiazolo[5,4-b]pyridine agonist of S1P1 and S1P5
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)ben
Cee, Victor J.,Frohn, Mike,Brian A. Lanman,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,Buerli, Roland W.
p. 107 - 112
(2011/04/15)
Development of a suitable physical form for a sphingosine-1-phosphate receptor agonist
AMG 369 (1), a novel S1P1 agonist, was selected for clinical development for the treatment of multiple sclerosis. Form B of the zwitterionic molecule was initially identified as a potential development form. However, because of the instability