Patent EA-004053-B1 (EA)
Title: Benzothiadiazine derivatives, preparation method, pharmaceutical compositions and use
Inventor: PIROTTE BERNARD
IPC: C07D285/24
Filed: 2000-11-28
Abstract: 1. Compound of formula (I) : wherein : X is atom of fluorine, bromine or iodine, or methyl group, R1 or R2, each being similar of different are hydrogen atom or linear or branched group (C1-C6) alkyl, its isomers, if exist, and their its addition salts with pharmaceutically acceptable acid. 2. Compound of formula (1) according to claim 1, which is 7-bromo-4-ethyl-2, 3-dihydro-4H-1,2,4-benzothiadiazine 1,1-dioxide. 3. Compound of formula (I) according to claim 1, which is 4-ethyl-7-iodo-2, 3-dihydro-4H-1,2,4-benzothiadiazine 1,1-dioxide. 4. Method of preparing of compounds of formula (I), characterized by reaction: wherein X has the same value, that in formula (I), with ethylorthoformiate, with the resulting compound of formula (III): wherein X corresponds to over mentioned definitions, then reaction of said product is held: - with reducing agent, with resulting compound of formula (Ia), which is particular case of compound of formula (I): wherein X corresponds to over mentioned definitions, and then if necessary this product is reacted with di(tert-butyl)bicarbonate, with resulting formula (IV): wherein X corresponds to over mentioned definitions and BOC means tert-butoxicarbonyl group, and then this product is reacted with formula (V): R`2-Y2 (V) wherein R`2 is linear or branched group (C1-C6)alkyl, Y2 is removable group, such as halogen atom or tosylate, mesylate or trifluoromethanesulfonate group, with receiving, after removing of protective group, of compound of formula (Ib), which is particular case of compounds of formula (I): wherein X and R`2 corresponds to over mentioned values, - or with compound of formula (VI) R`1-Y`1 (VI) wherein R`1 means linear or branched group (C1-C6)alkyl, and Y1 means removable group, such as halogen atom or tosylate, mesylate or trifluoromethanesulfonate group, with receiving, after recovery of compound of formula (Ic), which is particular case of compounds of formula (I): wherein X and R`2 corresponds to over mentioned values, then, if necessary this product is reacted with compound of formula (V), and with the resulting compound of formula (Id), which is particular case of compounds of formula (I): wherein X, R`1 and R`2 corresponds to over mentioned values, and these compounds with formulas (Ia), (Ib), (Ic) and (Id) are whole of compounds of formula (I), which, if necessary are cleaned by standard cleaning method, and transforming them, if necessary, in additional salts with pharmaceutically acceptable salts. 5. Pharmaceutical compositions, comprising as an acting substance, a compound according to any of claims 1-3, independently, or in combination with one or more inert, non-toxic, pharmaceutically acceptable carriers. 6. Use of pharmaceutical compositions according to claim 5 as medical preparations, as modulators AMPA. 7. Use of pharmaceutical compositions according to claim 6, as medical preparations, as mnemocognition amplifier. 8. Use of pharmaceutical compositions according to claim 6, as medical preparations while treating schizophrenia.