Abstract
A series of dual CCR3/H(1) antagonists based on a bispiperidine scaffold were discovered. Introduction of an acidic group overcame hERG liability. Bioavailability was optimised by modulation of physico-chemical properties and physical form to deliver a compound suitable for clinical evaluation.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Drug Discovery*
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Drug Interactions
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Histamine H1 Antagonists / chemistry*
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Histamine H1 Antagonists / pharmacokinetics
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Molecular Structure
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Piperidines / chemistry
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Rats
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Receptors, CCR3 / antagonists & inhibitors*
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Risk Factors
Substances
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CCR3 protein, human
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Ether-A-Go-Go Potassium Channels
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Histamine H1 Antagonists
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KCNH1 protein, human
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Piperidines
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Receptors, CCR3
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piperidine