Benzo[d]thiazol-2(3H)-ones as new potent selective CB2 agonists with anti-inflammatory properties

Eur J Med Chem. 2019 Mar 1:165:347-362. doi: 10.1016/j.ejmech.2018.12.008. Epub 2018 Dec 13.

Abstract

The high distribution of CB2 receptors in immune cells suggests their important role in the control of inflammation. Growing evidence offers this receptor as an attractive therapeutic target: selective CB2 agonists are able to modulate inflammation without triggering psychotropic effects. In this work, we report a new series of selective CB2 agonists based on a benzo[d]thiazol-2(3H)-one scaffold. This drug design project led to the discovery of compound 9, as a very potent CB2 agonist (Ki = 13.5 nM) with a good selectivity versus CB1. This compound showed no cytotoxicity, acceptable ADME-Tox parameters and demonstrates the ability to counteract colon inflammatory process in vivo.

Keywords: CB(2) agonist; Colon inflammatory; Inflammation.

MeSH terms

  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Benzothiazoles / chemistry
  • Benzothiazoles / pharmacology*
  • Cannabinoid Receptor Agonists / chemistry
  • Cannabinoid Receptor Agonists / pharmacology
  • Colon / pathology
  • Humans
  • Inflammation / drug therapy*
  • Receptor, Cannabinoid, CB2 / agonists*
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Benzothiazoles
  • Cannabinoid Receptor Agonists
  • Receptor, Cannabinoid, CB2