| 摘要 |
Disclosed are 1,1,1,3,3,3-hexafluoropropan-2-yl 4-benzyl-piperazine-1-carboxylate derivatives of the general formula (I), wherein L3 is -CH2-; R7 is phenyl, wherein R7 is substituted by two moieties independently selected from Rh; Ra and Rb are independently selected, for each occurrence, from the group consisting of hydrogen and alkyl; wherein alkyl may optionally be substituted by one or more substituents selected from fluorine, cyano, oxo, and hydroxyl; or Ra and Rb, when they occur together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring which may have an additional heteroatom selected from O, S, or N; wherein the 4-6 membered heterocyclic ring may optionally be substituted by one or more substituents selected from the group consisting of fluorine, cyano, oxo, and hydroxyl; Rh is selected from the group consisting of: halogen, cyano, alkyl (optionally substituted by one, two or three halogens), and RaRbN-; or a pharmaceutically acceptable salt or stereoisomer thereof. Representative compounds of formula (I) include 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-fluoro-4-morpholinobenzyl)piperazine-1-carboxylate, 1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[2-(morpholin-4-yl)-3-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate, 1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[2-chloro-6-(pyrrolidin-1-yl)phenyl]methyl]piperazine-1-carboxylate, 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(4-bromo-2-(piperidin-1-yl)benzyl)piperazine-1-carboxylate, and 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(azetidin-1-yl)-4-chlorobenzyl)piperazine-1-carboxylate. Also disclosed is a pharmaceutically acceptable composition comprising a compound as defined above, or a stereoisomer or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, for the treatment of pain, cancer, obesity or for the treatment or amelioration of Downs syndrome or Alzheimer’s disease. |
