Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

Iain R. Greig, Gemma L. Baillie, Mostafa Abdelrahman, Laurent Trembleau, Ruth A. Ross

Research output: Contribution to journalArticle

9 Citations (Scopus)
7 Downloads (Pure)

Abstract

Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes, for which pharmacokinetic properties have not been reported, but are expected to be sub-optimal. In this study, we show a novel series of indole sulfonamides which have greatly improved metabolic stability and permeability compared to the most widely-studied CB1 PAM (Org27569). Compound 6c (ABD1075) had potency of 3 nM and showed excellent oral exposure and CNS penetration, making it a highly versatile tool for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.
2009 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)4403-4407
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume26
Issue number18
Early online date6 Aug 2016
DOIs
Publication statusPublished - 15 Sep 2016

    Fingerprint

Keywords

  • cannabinoid
  • negative allosteric modulator
  • CB1NAM
  • indole sulfonamide

Cite this