Piperazine ,1-(2-methylphenyl)-Hydrochloride

Some type of inverse agonists, cannabinoid receptor 1 (CB1) has been shown to be an anti-obesity appetite suppressant drug candidate. However, the first generation of CB1 inverse agonist rimonabant (SR141716A) is indicated taranabant otenabant and are centrally acting, with a high degree of psychiatric side effects. Therefore, the discovery of CB1 inverse agonists can be separated with a chemical backbone of these promising for the development of peripheral CB1 inverse agonist effective with fewer side effects. We generated a new CB1 inverse agonists (4- (bis (4-fluorophenyl) methyl) piperazin-1-yl) (cyclohexyl) methanone (LDK1229), from the class of the analogs of benzhydryl piperazine. This compound selectively binds to more than CB1 receptor cannabinoid type 2, with a Ki of 220 nM. CB1 comparable binding was also observed analogues of 1- [bis (4-fluorophenyl) methyl] -4-cinnamyl piperazine (LDK1203) and 1- [bis (4-fluorophenyl) methyl] -4-piperazine tosyl (LDK1222) represented by the substitution on the piperazine ring, where the piperazine and LDK1203 LDK1222 are each substituted with an alkyl shift and a tosyl group. LDK1229 has a comparable efficacy SR141716A antagonize the baseline activity of the G protein coupling CB1, as indicated by a reduction of guanosine 5'-O- (3-thio) triphosphate binding. In accordance with the inverse agonist behavior, increased CB1 location of the cell surface after treatment with LDK1229 was also observed. Although reception and mutation analysis showed that LDK1229 shapes similar interactions with the case of receptor SR141716A the benzhydryl piperazine skeleton structurally inverse agonists of first generation CB1 receptors. It offers new opportunities for the development of novel CB1 inverse agonists by optimizing the molecular properties, such as the polar surface and hydrophilic properties to reduce SR141716A observed with the core activity.