Abstract
Substituted azaquinazolinones were identified as antagonists of the GHSr-1A receptor for the treatment of type II diabetes and obesity. Optimisation for potency and LogD lead to the identification of orally bioavailable, potent antagonists with improved selectivity over hERG.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Aza Compounds / chemical synthesis*
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Aza Compounds / pharmacokinetics
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Aza Compounds / pharmacology
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Biological Availability
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Diabetes Mellitus, Type 2 / drug therapy
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Diabetes Mellitus, Type 2 / metabolism
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Drug Design
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Hydrophobic and Hydrophilic Interactions
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology
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Kinetics
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Male
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Obesity / drug therapy
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Obesity / metabolism
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Quinazolinones / chemical synthesis*
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Quinazolinones / pharmacokinetics
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Quinazolinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Ghrelin / antagonists & inhibitors*
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Receptors, Ghrelin / metabolism
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Structure-Activity Relationship
Substances
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Aza Compounds
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Ether-A-Go-Go Potassium Channels
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Hypoglycemic Agents
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Quinazolinones
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Receptors, Ghrelin