1,6-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase inhibitors

Shawn Maddaford, Paul Renton, Joanne Speed, Subhash C. Annedi, Jailall Ramnauth, Suman Rakhit, John Andrews, Gabriela Mladenova, Lisa Majuta, Frank Porreca

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


A series of 1,6-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). By varying the basic amine side chain at the 1-position of the indole ring, several potent and selective inhibitors of human neuronal NOS were identified. In general compounds with bulkier side chains displayed increased selectivity for nNOS over eNOS and iNOS isoforms. One of the compounds, (R)-8 was shown to reduce tactile hyperesthesia (allodynia) after oral administration (30 mg/kg) in an in vivo rat model of dural inflammation relevant to migraine pain.

Original languageEnglish (US)
Pages (from-to)5234-5238
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number18
StatePublished - Sep 15 2011


  • 1,6-Disubstitued indole derivatives
  • Nitric oxide
  • Nitric oxide synthase
  • Nitric oxide synthase inhibitors
  • Selective neuronal nitric oxide synthase inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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