| 摘要 |
600416 Disclosed are 5-bicycloheteroarylalkyl-3-phenyl-1,2,4-triazole derivatives as represented by the general formula (I), wherein: HET-1 is a heteroaromatic group of formula II containing from 2 to 4 nitrogen atoms, and which is preferably selected from [1,2,4]triazolo[1,5-a]pyridine, [1,2,4]triazolo[1,5-a]pyrimidine or [1,2,4]triazolo[1,5-a]pyrazine, and which may be optionally substituted; Q is phenyl, optionally substituted with one to five substituents, or a monocyclic 5-membered or 6-membered heteroaromatic group containing 1 or 2 heteroatoms; L is a linker selected from S-CH2, CH2-S, ethylene, ethenylene or ethynylene; R1 is selected from H, alkyl, alkylcycloalkyl, hydroxyalkyl, CH2CN, CH2C(O)NH2, arylalkyl or alkylheterocycloalkyl; and tautomers, pharmaceutically acceptable salts and polymorphic forms thereof. Important compounds include 8-methoxy-5-methyl-2-(5-phenyl-2H-[1,2,4]triazol-3-ylsulfanylmethyl)-[1,2,4]triazolo[1,5-a]pyridine, 8-methyl-2-[2-(2-methyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyridine, 5,7-dimethyl-2-[2-(2-methyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine, 5,8-dimethyl-2-[2-(2-methyl-5-phenyl-2H-[1,2,4]triazol-3-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyrazine, 3-{ 5-[2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-ethyl]-3-phenyl-[1,2,4]triazol-1-yl} -propionitrile and 3-{ 5-[2-(5,8-dimethyl-[1,2 ,4]triazolo[1,5-a]pyrazin-2-yl)-ethyl]-3-phenyl-[1,2,4]triazol-1-yl} -propylamine. Also disclosed is a pharmaceutical composition comprising a therapeutically effective amount of a compound as defined above, and one or more pharmaceutically acceptable carriers, diluents and excipients, for the treatment of a neurodegenerative or psychiatric disorder, alone or in combination with one or more neuroleptic agents such as sertindole, olanzapine, risperidone, quetiapine, aripiprazole, haloperidol, clozapine, ziprasidone and osanetant, including disorders such as Alzheimer's disease, multi-infarct dementia, alcoholic dementia or other drug-related dementia, dementia associated with intracranial tumors or cerebral trauma, dementia associated with Huntington's disease or Parkinson's disease, or AIDS related dementia, delirium, amnestic disorder, post-traumatic stress disorder, mental retardation, learning disorders, attention-deficit/hyperactivity disorder, age-related cognitive decline, schizophrenia etc. etc..
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