2. Academic Validation
  3. Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity

Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity

  • Bioorg Med Chem Lett. 2009 Apr 1;19(7):1916-20. doi: 10.1016/j.bmcl.2009.02.057.
Jana A Lewis 1,  Sarah A Scott,  Robert Lavieri,  Jason R Buck,  Paige E Selvy,  Sydney L Stoops,  Michelle D Armstrong,  H Alex Brown,  Craig W Lindsley
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
PMID: 19268584 DOI: 10.1016/j.bmcl.2009.02.057
Abstract

This Letter describes the synthesis and structure-activity-relationships (SAR) of isoform-selective PLD inhibitors. By virtue of the installation of alternative halogenated piperidinyl benzimidazolone privileged structures, in combination with a key (S)-methyl group, novel PLD inhibitors with low nM potency and unprecedented levels of PLD1 isoform selectivity (approximately 1700-fold) over PLD2 were developed.

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