Abstract
This Letter describes the synthesis and structure-activity relationships (SAR) of isoform-selective PLD inhibitors. By virtue of the installation of a 1,3,8-triazaspiro[4,5]decan-4-one privileged structure, PLD inhibitors with nanomolar potency and an unprecedented 40-fold selectivity for PLD2 over PLD1 were developed. Interestingly, SAR for this diverged from our earlier efforts, and dual PLD1/2 inhibitors were also discovered within this series.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Dose-Response Relationship, Drug
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Phospholipase D / antagonists & inhibitors*
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Phospholipase D / metabolism
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Isoenzymes
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phospholipase D2
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Phospholipase D
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phospholipase D1