2. Academic Validation
  3. Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

  • Bioorg Med Chem Lett. 2016 Sep 15;26(18):4403-4407. doi: 10.1016/j.bmcl.2016.08.018.
Iain R Greig 1,  Gemma L Baillie 2,  Mostafa Abdelrahman 3,  Laurent Trembleau 4,  Ruth A Ross 2
Affiliations

Affiliations

  • 1 Kosterlitz Centre for Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. Electronic address: i.greig@abdn.ac.uk.
  • 2 Kosterlitz Centre for Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK; Department of Pharmacology and Toxicology, University of Toronto and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5S 1A8, Canada.
  • 3 Laboratory of Supramolecular Chemistry, School of Natural and Computing Sciences, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt.
  • 4 Laboratory of Supramolecular Chemistry, School of Natural and Computing Sciences, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK.
PMID: 27542310 DOI: 10.1016/j.bmcl.2016.08.018
Abstract

Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.

Keywords

CB1 NAM; Cannabinoid; Indole sulfonamide; Negative allosteric modulator.

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