4-(Fluorinated alkyl or fluorinated cycloalkylalkyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-diox ide derivatives (I) are new. - Benzothiadiazine derivatives of formula (I) (including optical isomers where appropriate) and their acid or base addition salts are new. - Rf = mono- or polyfluoroalkyl or mono- or polyfluoro-cycloalkylalkyl; - R1 = H, alkylaminocarbonyl or alkyl (optionally substituted by one or more halo); - R2 = H, halo, cycloalkyl or alkyl (optionally substituted by one or more halo); - R3 - R6 = H, halo, NO2, CN, alkylsulfonyl, OH, alkoxy, alkyl (optionally substituted by one or more halo) or NH2 (optionally substituted by 1 or 2 alkyl); - Alkyl moieties have 1-6C and cycloalkyl moieties 3-7C; - provided that R3 = H when R6 is other than H. - Independent claims are also included for: - (A) new benzothiadiazine derivatives of formula (VI); and - (B) the preparation of (I). - ACTIVITY - Nootropic; Tranquilizer; Antidepressant; Neuroprotective; Antiparkinsonian; Anticonvu lsant; Neuroleptic. - In object recognition tests in 17 month old rats, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazin e-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.
NEW FLUORINATED BENZOTHIADIAZINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.