| 摘要 |
4-(Fluorinated alkyl or fluorinated cycloalkylalkyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide derivatives (I) are new. Benzothiadiazine derivatives of formula (I) (including optical isomers where appropriate) and their acid or base addition salts are new. R fmono- or polyfluoroalkyl or mono- or polyfluoro-cycloalkylalkyl; R 1H, alkylaminocarbonyl or alkyl (optionally substituted by one or more halo); R 2H, halo, cycloalkyl or alkyl (optionally substituted by one or more halo); R 3 - R 6H, halo, NO 2, CN, alkylsulfonyl, OH, alkoxy, alkyl (optionally substituted by one or more halo) or NH 2 (optionally substituted by 1 or 2 alkyl); Alkyl moieties have 1-6C and cycloalkyl moieties 3-7C; provided that R 3 = H when R 6 is other than H. Independent claims are also included for: (A) new benzothiadiazine derivatives of formula (VI); and (B) the preparation of (I). [Image] [Image] ACTIVITY : Nootropic; Tranquilizer; Antidepressant; Neuroprotective; Antiparkinsonian; Anticonvulsant; Neuroleptic. In object recognition tests in 17 month old rats, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide (Ia) at oral doses of 0.1 mg/kg significant reduced age-associated loss of memory. MECHANISM OF ACTION : alpha -Amino-5-methyl-4-isoxazole-propionic acid (AMPA) receptor modulator. In tests in Xenopus ovocytes, (Ia) strongly potentiated the excitative effect of AMPA, showing EC2X and EC5X values of 6.7 mu M and 14.5 mu M respectively for increasing the AMPA-inducedionic current. |
