Abstract
A novel series of pyrrolidine heterocycles was prepared and found to show potent inhibitory activity of CCR1 binding and CCL3 mediated chemotaxis of a CCR1-expressing cell line. A potent, optimized triazole lead from this series was found to have acceptable pharmacokinetics and microsomal stability in rat and is suitable for further optimization and development.
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Cell Line
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Chemokine CCL3 / immunology*
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Chemotaxis / drug effects*
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Microsomes, Liver / metabolism
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Pyrrolidines / chemistry*
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Pyrrolidines / metabolism
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Pyrrolidines / pharmacokinetics
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Pyrrolidines / pharmacology*
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Rats
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Receptors, CCR1 / antagonists & inhibitors*
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Receptors, CCR1 / immunology
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Triazoles / chemistry
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Triazoles / metabolism
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Triazoles / pharmacokinetics
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Triazoles / pharmacology
Substances
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Chemokine CCL3
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Pyrrolidines
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Receptors, CCR1
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Triazoles
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pyrrolidine