Design of a novel pyrrolidine scaffold utilized in the discovery of potent and selective human β 3 adrenergic receptor agonists

GJ Morriello, HR Wendt, A Bansal, J Di Salvo…

Index: Morriello, Gregori J.; Wendt, Harvey R.; Bansal, Alka; Salvo, Jerry Di; Feighner, Scott; He, Jiafang; Hurley, Amanda L.; Hreniuk, Donna L.; Salituro, Gino M.; Reddy, Marat Vijay; Galloway, Sheila M.; McGettigan, Katherine K.; Laws, George; McKnight, Crystal; Doss, George A.; Tsou, Nancy N.; Black, Regina M.; Morris, Judy; Ball, Richard G.; Sanfiz, Anthony T.; Streckfuss, Eric; Struthers, Mary; Edmondson, Scott D. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 6 p. 1865 - 1870

Full Text: HTML

Citation Number: 7

Abstract

A novel class of human β3-adrenergic receptor agonists was designed in effort to improve selectivity and metabolic stability versus previous disclosed β3-AR agonists. As observed, many of the β3-AR agonists seem to need the acyclic ethanolamine core for agonist activity. We have synthesized derivatives that constrained this moiety by introduction of a pyrrolidine. This unique modification maintains human β3 functional potency with improved selectivity ...