Abstract
A series of 1, 2, 4-oxadiazole derivatives have been designed and synthesized, and 25 compounds were evaluated their abilities by the assay of cAMP concentration in GPR119-transfected HEK293T cells. All compounds showed acceptable agonistic effects on GPR119. Among these compounds, 4p exhibited the best agonistic effects with the EC50 of 20.6 nm, which was comparable to that of positive control GPR119 agonist GSK1292263. The agonistic activity of these 1,2,4-oxadiazole derivatives led to the establishment of a structure-activity relationship.
Keywords:
GPCR; GPR119; SAR study; agonistic activity; cAMP.
© 2016 John Wiley & Sons A/S.
Publication types
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Letter
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclic AMP / metabolism
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Drug Design
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Drug Evaluation, Preclinical
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HEK293 Cells
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Humans
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / metabolism
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Mesylates / chemistry
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Mesylates / metabolism
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Oxadiazoles / chemical synthesis
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Oxadiazoles / chemistry*
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Oxadiazoles / metabolism
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Protein Binding
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Receptors, G-Protein-Coupled / agonists*
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Structure-Activity Relationship
Substances
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(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonate
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GPR119 protein, human
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Hypoglycemic Agents
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Mesylates
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Oxadiazoles
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Receptors, G-Protein-Coupled
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Cyclic AMP