Abstract
GPR120 is an attractive target for the treatment of type 2 diabetes. In this study, a series of biphenyl derivatives were designed, synthesized by hybrid design. The selected compound 6a exhibited potent GPR120 agonist activity (EC50 = 93 nM) and high selectivity over GPR40. The results of oral glucose tolerance test (OGTT) demonstrated that 6a exhibited significant glucose-lowering effect in glucose-loaded ICR male mice. Analysis of the structure-activity relationship is also presented. Compound 6a deserves further biological evaluation and structural modifications.
Keywords:
Agonist biphenyl derivatives; GPR120; OGTT; Type 2 diabetes.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biphenyl Compounds / administration & dosage
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology*
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Biphenyl Compounds / therapeutic use
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Blood Glucose / analysis
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Diabetes Mellitus, Experimental / blood
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Type 2 / blood
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Diabetes Mellitus, Type 2 / drug therapy
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Dose-Response Relationship, Drug
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Drug Discovery*
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Glucose Tolerance Test
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / pharmacology*
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Hypoglycemic Agents / therapeutic use
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Male
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Mice, Inbred ICR
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Receptors, G-Protein-Coupled / agonists*
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Structure-Activity Relationship
Substances
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Biphenyl Compounds
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Blood Glucose
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FFAR4 protein, mouse
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Hypoglycemic Agents
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Receptors, G-Protein-Coupled