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

14 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

  • General Chemistry

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