Abstract
The synthesis and structure-activity-relationships (SARs) of novel 2-(pyridine-2-yl)-1H-benzimidazole glucokinase activators are described. Systematic modification of benzimidazole lead 5a identified from a high-throughput screening led to the discovery of a potent and metabolically stable glucokinase activator 16p(R) with greater structural diversity from GKAs reported to date. The compound also demonstrated acute oral glucose lowering efficacy in rat OGTT model.
MeSH terms
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Allosteric Site
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Animals
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / pharmacology
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Binding Sites
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Chemistry, Pharmaceutical / methods
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Diabetes Mellitus, Experimental / drug therapy
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Drug Design
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Enzyme Activation
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Glucokinase / metabolism*
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Glucose Tolerance Test
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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / pharmacology
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Models, Chemical
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Molecular Conformation
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Rats
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Structure-Activity Relationship
Substances
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Benzimidazoles
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Hypoglycemic Agents
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benzimidazole
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Glucokinase