Abstract
We disclosed a novel series of G-protein coupled receptor 119 (GPR119) agonists based on a bicyclic amine scaffold. Through the optimization of hit compound 1, we discovered that the basic nitrogen atom of bicyclic amine played an important role in GPR119 agonist activity expression and that an indanone in various bicyclic rings was suitable in this series of compounds. The indanone derivative 2 showed the effect of plasma glucose control in oGTT and scGTT in the rodent model.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Amines / chemical synthesis
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Amines / chemistry*
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Amines / pharmacology
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Animals
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Blood Glucose / drug effects
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Blood Glucose / metabolism
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Bridged Bicyclo Compounds / chemistry*
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Glucose Tolerance Test
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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 / pharmacology
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Indans / chemical synthesis*
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Indans / chemistry
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Indans / pharmacology
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Mice
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Mice, Inbred C57BL
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Protein Binding
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Receptors, G-Protein-Coupled / agonists*
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Receptors, G-Protein-Coupled / metabolism
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Structure-Activity Relationship
Substances
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Amines
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Blood Glucose
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Bridged Bicyclo Compounds
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GPR119 protein, human
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Hypoglycemic Agents
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Indans
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Pyrimidines
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Receptors, G-Protein-Coupled
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indacrinone