Discovery of 1,1-dioxo-1,2,6-thiadiazine-5-carboxamide derivatives as cannabinoid-like molecules with agonist and antagonist activity

A series of new 2-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxylate derivatives have been prepared from monosubstituted sulfamides in order to obtain N-substituted1,1-dioxo-1,2,6-thiadiazine-5-carboxamides as novel cannabinoid derivatives, analogues of Rimonabant (SR141716A). Their potential functional activity on cannabinoid receptors has been evaluated in vitro and in vivo in mice, showing that two compounds (37 and 39) behave as cannabinoid agonists in vitro. Their potency is lower than that of the reference compound, WIN 55,212-2, but their efficacy is similar to that of this cannabinoid agonist, although no in vivo activity is observed. Another derivative (38) behaves as a cannabinoid antagonist both in vitro and in vivo, being its efficacy and potency similar to that of the well-known antagonist SR141716A. (c) 2007 Elsevier Ltd. All rights reserved.