| 摘要 |
A carboxamide derivative of the Formula (I) useful in the treatment and/prevention of anxiety, mania, depression, panic disorders and/or aggression, disorders associated with subarachnoid haemorrhage or neural shock, the effects associated with withdrawal from substances of abuse such as cocaine, nicotine, alcohol and benzadiazepines, disorders treatable and/or preventable with anti-convulsive agents, such as epilepsy including post traumatic epilepsy, Parkinson's disease, psychosis, migraine, cerebral ischaemia, Alzheimer's disease and other degenerative diseases such as Huntington's chorea, schizophrenia, obsessive compulsive disorders, neurological deficits associated with AIDS, sleep disorders (including circadian rhythm disorders, insomnia and narcolepsy), tics (e.g. Giles de la Tourette's syndrome), traumatic brain injury, tinnitus, neuralgia, especially trigeminal neuralgia, neuropathic pain, dental pain, cancer pain, inappropriate neuronal activity resulting in neurodysthesias in diseases such as diabetes, multiple sclerosis (MS) and motor neuron disease, ataxias, muscular rigidity (spasticity), temporomandibular joint dysfunction and amyotrophic lateral sclerosis (ALS). The processes for making compounds of Formula (I) are described. Wherein; R1 is hydrogen, C1-6alkyl (optionally substituted by hydroxy or C1-4alkoxy), C1-6alkenyl, C1-6alkynyl, C1-6alkyICO-, formyl, CF3CO- or C1-6alkyISO2-; R2 is hydrogen or up to three substituents selected from halogen, NO2, CN, N3, CF3O-, CF3S-, CF3CO-, trifluoromethyldiazirinyl, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6perfluoroalkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl-, C1-6alkyIO-, C1-6alkyICO-, C3-6cycloalkyI0-, C3-6cycloalkyICO-, C3-6cycloalkylC l-4alkyl 0-, C 3-6cycloalkyl-C1-4alkyICO-, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C1-4alkyl-, C1-6alkyIS-, C1-6alkylSO2-, (C1-4alkyl)2NSO2-, (C1-4alkyl)NHSO2-, (C1-4alkyl)2NCO-, (C1-4alkyl)NHCO- or CONH2; or -NR5R6 where R5 is hydrogen or C1-4alkyl, and R6 is hydrogen, C1-4alkyl, formyl, -CO2C1-4alkyl or -COC1-4alkyl; or two R -groups together form a carbocyclic ring that is saturated or unsaturated and un-substituted or substituted by -OH or =O; and the two R3 groups and the two R4 groups are each independently hydrogen or C1-6alkyl or the two R3 groups and/or the two R4 groups together form a C3-6spiroalkyl group provided that at least one R3 or R4 group is not hydrogen; provided that the compound is not 1-methyl-6-benzoylamino-l,2,3,4tetrahydroisoquinoline, or 1,2-dimethyl-6-benzoylamino-1,2,3,4tetrahydroisoquinoline.
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