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

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. [Display omitted] •A series of novel benzo[d]thiazol-2(3H)-ones was designed and synthesized.•Compound 9 has shown CB2 affinity in the nanomolar range, no cytotoxicity, and acceptable ADME-Tox parameters.•Compound 9 has demonstrated the ability to counteract colon inflammatory process in vivo.