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  • Title: Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 1,3,8-triazaspiro[4,5]decan-4-one privileged structure that engenders PLD2 selectivity.
    Author: Lavieri R, Scott SA, Lewis JA, Selvy PE, Armstrong MD, Alex Brown H, Lindsley CW.
    Journal: Bioorg Med Chem Lett; 2009 Apr 15; 19(8):2240-3. PubMed ID: 19299128.
    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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