412311-88-7Relevant articles and documents
Design, synthesis, and evaluation of conformationally restricted acetanilides as potent and selective β3 adrenergic receptor agonists for the treatment of overactive bladder
Moyes, Christopher R.,Berger, Richard,Goble, Stephen D.,Harper, Bart,Shen, Dong-Ming,Wang, Liping,Bansal, Alka,Brown, Patricia N.,Chen, Airu S.,Dingley, Karen H.,Di Salvo, Jerry,Fitzmaurice, Aileen,Gichuru, Loise N.,Hurley, Amanda L.,Jochnowitz, Nina,Miller, Randall R.,Mistry, Shruty,Nagabukuro, Hiroshi,Salituro, Gino M.,Sanfiz, Anthony,Stevenson, Andra S.,Villa, Katherine,Zamlynny, Beata,Struthers, Mary,Weber, Ann E.,Edmondson, Scott D.
, p. 1437 - 1453 (2014/03/21)
A series of conformationally restricted acetanilides were synthesized and evaluated as β3-adrenergic receptor agonists (β3-AR) for the treatment of overactive bladder (OAB). Optimization studies identified a five-membered ring as the preferred conformational lock of the acetanilide. Further optimization of both the aromatic and thiazole regions led to compounds such as 19 and 29, which have a good balance of potency and selectivity. These compounds have significantly reduced intrinsic clearance compared to our initial series of pyridylethanolamine β3-AR agonists and thus have improved unbound drug exposures. Both analogues demonstrated dose dependent β3-AR mediated responses in a rat bladder hyperactivity model.
