Journal : Eur J Med Chem
Title : Benzo[d]thiazol-2(3H)-ones as new potent selective CB<sub>2</sub> agonists with anti-inflammatory properties.
Year : 2019
Volume : 165
First Page : 347
Last Page : 362
Authors : Leleu-Chavain N, Baudelet D, Heloire VM, Rocha DE, Renault N, Barczyk A, Djouina M, Body-Malapel M, Carato P, Millet R.
Abstract : The high distribution of CB<sub>2</sub> receptors in immune cells suggests their important role in the control of inflammation. Growing evidence offers this receptor as an attractive therapeutic target: selective CB<sub>2</sub> agonists are able to modulate inflammation without triggering psychotropic effects. In this work, we report a new series of selective CB<sub>2</sub> 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 CB<sub>2</sub> agonist (K<sub>i</sub> = 13.5 nM) with a good selectivity versus CB<sub>1</sub>. This compound showed no cytotoxicity, acceptable ADME-Tox parameters and demonstrates the ability to counteract colon inflammatory process in vivo.
