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Conformational restriction in a series of GPR119 agonists: differences in pharmacology between mouse and human.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Jun 01; Vol. 23 (11), pp. 3175-9. Date of Electronic Publication: 2013 Apr 10. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Biological Availability
Bridged Bicyclo Compounds, Heterocyclic chemical synthesis
Bridged Bicyclo Compounds, Heterocyclic pharmacokinetics
Cell Membrane Permeability drug effects
Cyclic AMP metabolism
Dogs
Half-Life
Heterocyclic Compounds, 2-Ring chemical synthesis
Heterocyclic Compounds, 2-Ring pharmacokinetics
Humans
Madin Darby Canine Kidney Cells
Mice
Protein Binding
Pyrimidines chemical synthesis
Pyrimidines pharmacokinetics
Receptors, G-Protein-Coupled metabolism
Structure-Activity Relationship
Bridged Bicyclo Compounds, Heterocyclic chemistry
Heterocyclic Compounds, 2-Ring chemistry
Pyrimidines chemistry
Receptors, G-Protein-Coupled agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 23
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 23628336
- Full Text :
- https://doi.org/10.1016/j.bmcl.2013.04.006