| 摘要 |
602312 The disclosure relates to heterocyclic derivatives as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water. Conditions which may be treated by the compounds of the disclosure include: Kennedy’s disease, duodenal cancer with or without Helicobacter pylori infections, colorectal cancer, Zolliger-Ellison syndrome, gastric cancer with or without Helicobacter pylori infections, pathogenic psychotic conditions, schizophrenia, infertility, neoplasia, inflammatory host responses, cancer, malign metastasis, melanoma, psoriasis, impaired humoral and cell-mediated immune responses, leukocyte adhesion and migration processes in the endothelium, impaired food intake, impaired sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance or impaired regulation of body fluids, multiple sclerosis, the Guillain-Barré syndrome and chronic inflammatory demyelinizing polyradiculoneuropathy Compounds of the disclosure include: 3-(2,2,2-Trifluoroethoxy)-1-(1H-benzo[d]imidazol-5-yl)-5-(2,3-difluorophenyl)-4-methyl-1H-pyrrol-2(5H)-one, 3-(2,2,3,3-Tetrafluoropropoxy)-1-(1H-benzo[d]imidazol-5-yl)-5-(2,3-difluoro-phenyl)-4-methyl-1H-pyrrol-2(5H)-one, 1-(1 H-Benzo[d]imidazol-6-yl)-3-methoxy-4-methyl-5-(4-(1-methylpiperidin-4-yl)phenyl)-1H-pyrrol-2(5H)-one, 1-(1H-Benzo[d]imidazol-6-yl)-5-(4-(cyclohexyloxy)phenyl)-3-methoxy-4-methyl-1H-pyrrol-2(5H)-one, 1-(1H-Benzo[d]imidazol-6-yl)-5-(2,3-difluorophenyl)-3-methoxy-4-propyl-1H-pyrrol-2(5H)-one And 1-(1 H-Benzo[d]imidazol-6-yl)-5-cyclohexyl-3-methoxy-4-methyl-1H-pyrrol-2(5H)-one |
