5,6-diaryl-pyrazine-2-amide derivatives as CB1 antagonists.

摘要

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts, prodrugs, solvates and crystalline forms thereof, in which R¹ and R² independently represent: a C_1-6alkyl group; an optionally substituted (amino)C_1-4alkyl-group; an optionally substituted non-aromatic C_3-15carbocyclic group; a (C_3-12cycloalkyl)C_1-3alkyl-group; a group -(CH₂)_r(phenyl)_s in which r is 0, 1, 2, 3 or 4, s is 1 when r is 0 otherwise s is 1 or 2 and the phenyl groups are optionally independently substituted by Z; naphthyl; anthracenyl; an optionally substituted saturated 5 to 8 membered heterocyclic group containing one nitrogen and optionally one of the following: oxygen, sulphur or an additional nitrogen; 1-adamantylmethyl; a group -(CH₂)_t Het in which t is 0, 1, 2, 3 or 4, and the alkylene chain is optionally substituted and Het represents an optionally substituted aromatic heterocycle; or R¹ represents H and R² is as defined above; or R¹ and R² together with the nitrogen atom to which they are attached represent a saturated optionally substituted 5 to 8 membered heterocyclic group as defined above; X is CO or SO₂; Y is absent or represents NH optionally substitututed by a C_1-3alkyl group; R³ and R⁴ independently represent phenyl, thienyl or pyridyl substituted by Z; Z represents a C_1-3alkyl group, a C_1-3alkoxy group, hydroxy, halo, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, trifluoromethylsulphonyl, nitro, amino, mono or di C_1-3alkylamino, mono or di C_1-3alkylamido, C_1-3alkylsulphonyl, C_1-3alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C_1-3alkyl carbamoyl, sulphamoyl and acetyl; and R⁵ is H, a C_1-3alkyl group, a C_1-3alkoxymethyl group, trifluoromethyl, a hydroxyC_1-3alkyl group, C_1-3alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C_1-3alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula -CONHNR^aR^b; with the provisos; and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.