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)
6 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

Cannabinoid Receptors
Pulse amplitude modulation
Pharmacokinetics
Cannabinoids
Sulfonamides
Modulators
Permeability
Modulation
Therapeutics
indole
5-chloro-3-ethyl-1H-indole-2-carboxylic acid (2-(4-piperidin-1-yl-phenyl)ethyl)amide

Keywords

  • cannabinoid
  • negative allosteric modulator
  • CB1NAM
  • indole sulfonamide

Cite this

Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators. / Greig, Iain R.; Baillie, Gemma L.; Abdelrahman, Mostafa; Trembleau, Laurent; Ross, Ruth A.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 26, No. 18, 15.09.2016, p. 4403-4407.

Research output: Contribution to journalArticle

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AU - Baillie, Gemma L.

AU - Abdelrahman, Mostafa

AU - Trembleau, Laurent

AU - Ross, Ruth A.

N1 - This Letter was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Scottish Universities Life Sciences Alliance (SULSA) in 2011

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AB - 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.

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