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Conformational restriction in a series of GPR119 agonists: Differences in pharmacology between mouse and human |
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| Authors: | James S. Scott Katy J. Brocklehurst Hayley S. Brown David S. Clarke Helen Coe Sam D. Groombridge David Laber Philip A. MacFaul Darren McKerrecher Paul Schofield |
| Affiliation: | Cardiovascular & Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK |
| 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. |
| Keywords: | G-protein coupled receptors GPR119 agonists Pharmacology Partial agonists |
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