Tethered dimer inhibitors of NAD synthetase: Parallel synthesis of an aryl-substituted SAR library

Sadanandan E. Velu, Chi Hao Luan, Lawrence J. DeLucas, Christie G. Brouillette, Wayne J. Brouillette*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    13 Scopus citations

    Abstract

    We previously reported that tethered dimers containing indoles on one end and a permanent positive charge on the other, using a 6-9 carbon polymethylene tether, provided NAD synthetase inhibitors with impressive antibacterial activities against Gram-positives. Here, we report that the phenyl ring is a good substitute for indole, and we utilize solution-phase parallel synthesis to explore structure-activity relationships for substituents on that ring. General conclusions are that nonpolar substituents are more effective than polar ones and that different positional isomers often have very different enzyme inhibition activities. This latter observation reveals that enzyme activity is sensitive to minor structural changes and suggests that nonspecific detergent actions are not important for the observed effects.

    Original languageEnglish (US)
    Pages (from-to)898-904
    Number of pages7
    JournalJournal of Combinatorial Chemistry
    Volume7
    Issue number6
    DOIs
    StatePublished - Nov 2005

    ASJC Scopus subject areas

    • Chemistry(all)

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