Abstract
Design and optimization of a novel series of imidazo[1,2-b]pyridazine PDE10a inhibitors are described. Compound 31 displays excellent pharmacokinetic properties and was also evaluated as an insulin secretagogue in vitro and in vivo.
Keywords:
Brain penetration; GPCR; GSIS; Insulin secretagogues; PDE10a inhibitor; Type 2 diabetes.
Copyright © 2016 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Binding Sites
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Drug Design*
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Glucose Tolerance Test
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Half-Life
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacokinetics
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Insulin / metabolism
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Molecular Docking Simulation
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Phosphodiesterase Inhibitors / chemical synthesis
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Phosphodiesterase Inhibitors / chemistry*
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Phosphodiesterase Inhibitors / pharmacokinetics
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Phosphoric Diester Hydrolases / chemistry*
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Phosphoric Diester Hydrolases / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacokinetics
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
Substances
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Imidazoles
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Insulin
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Phosphodiesterase Inhibitors
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Pyridines
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imidazopyridine
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PDE10A protein, human
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Phosphoric Diester Hydrolases