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Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the
Robert Lavieri1, Sarah A Scott, Jana A Lewis
1Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
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.
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