Design, synthesis, and evaluation of conformationally restricted acetanilides as potent and selective β3 adrenergic receptor agonists for the treatment of overactive …

CR Moyes, R Berger, SD Goble, B Harper…

Index: 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. Journal of Medicinal Chemistry, 2014 , vol. 57, # 4 p. 1437 - 1453

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Citation Number: 9

Abstract

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. ...