Abstract
A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Benzopyrans / chemical synthesis*
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Benzopyrans / pharmacology
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Bradykinin B1 Receptor Antagonists*
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Carrageenan / pharmacology
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Chemistry, Pharmaceutical / methods
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Chronic Pain / drug therapy
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Drug Design
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Humans
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Hyperalgesia / drug therapy
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Inhibitory Concentration 50
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Kinetics
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Models, Chemical
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Rabbits
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / metabolism
Substances
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5-chlorochromenone
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Benzopyrans
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Bradykinin B1 Receptor Antagonists
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Tumor Necrosis Factor-alpha
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Carrageenan