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ID: ALA2380211

Journal: Bioorg Med Chem Lett

Title: Conformational restriction in a series of GPR119 agonists: differences in pharmacology between mouse and human.

Authors: Scott JS, Brocklehurst KJ, Brown HS, Clarke DS, Coe H, Groombridge SD, Laber D, MacFaul PA, McKerrecher D, Schofield P.

Abstract: A series of conformationally restricted GPR119 agonists were prepared based around a 3,8-diazabicyclo[3.2.1]octane scaffold. Examples were found to have markedly different pharmacology in mouse and human despite similar levels of binding to the receptor. This highlights the large effects on GPCR phamacology that can result from small structural changes in the ligand, together with inter-species differences between receptors.

CiteXplore: 23628336

DOI: 10.1016/j.bmcl.2013.04.006