Abstract
Conformationally constrained spirocycles (17-23) and (31-36) were synthesised. In vitro data revealed that these compounds are CCR1 antagonists with sub-nanomolar potency. In a functional assay 22, 23 and 36 inhibited CCR1 mediated chemotaxis with an IC50 value of 2, 2.6 and 68nM, respectively.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Caco-2 Cells
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Cell Line
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Chemotaxis / drug effects
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Humans
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Microsomes, Liver / metabolism
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Piperidines / chemistry
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Protein Binding
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Rats
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Receptors, CCR1 / antagonists & inhibitors*
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Receptors, CCR1 / metabolism
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Spiro Compounds / chemistry*
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Spiro Compounds / metabolism
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Spiro Compounds / pharmacology
Substances
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Piperidines
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Receptors, CCR1
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Spiro Compounds
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piperidine