NOVEL O-(3-AMINO-2-HYDROXYPROPYL)-HYDROXIMIC ACID HALIDES AND PROCESS FOR PREPARING THE SAME

The present invention relates to novel hydroximic acid halides, the preparation of the same, pharmaceutical compositions containing the above novel compounds as active ingredients as well as the use of the said compounds in the therapy of diabetic angiopathy. The novel hydroximic acid derivatives are illustrated by the general formula (I), wherein X is halo, such as fluoro, chloro, bromo and iodo R is hydrogen or C1-5alkyl R is C1-5alkyl, C5-7cycloalkyl or phenyl optionally substituted with hydroxy, or R and R , when taken together with the adjacent nitrogen, form a 5 to 8 membered ring optionally containing additional nitrogen and/or oxygen atom, which ring may also be condensed with a benzene ring R is hydrogen, phenyl, naphthyl or piridyl optionally substituted with one or more halo or alkoxy R is hydrogen or phenyl R is hydrogen or phenyl m is 0, 1 or 2 and n is 0, 1 or 2. PROCEDIMIENTO DE PREPARACION DE NUEVOS HALUROS DEL ACIDO O-(3-AMINO-2-HIDROXIPROPIL)-HIDROXIMICO. LA INVENCION SE RELACIONA CON UN PROCEDIMIENTO DE PREPARACION DE NUEVOS DERIVADOS DEL ACIDO HIDROXIMIXO DE FORMULA GENERAL (I), EN LA QUE X ES HALOGENO, RSI1 ES HIDROGENO O ALQUILO, RSI2 ES ALQUILO CSI1-5 O CICLOALQUILO, O RSI1 Y RSI2 FORMAN CONJUNTAMENTE CON N UN HETEROANILLO, RSI3 ES HIDROGENO, FENILO, NAFTILO O PIRIDILO, RSI4 Y RSI5 SON HIDROGENO O FENILO, M Y N VARIAN DE 0 A 2, PROCEDIMIENTO CARACTERIZADO PORQUE SE HACE REACCIONAR UNA ALDOXIMA CON UNA N,N-(RSI1,RSI2)-HIDROXI-HALOAMINA O UNA N,N-(RSI1,RSI2)-EPOXIAMINA O EPICLORIDRINA Y UNA RSI1,RSI2-AMINA, PARA DAR LOS COMPUESTOS DE REFERENCIA TRAS TRATAMIENTO EVENTUAL CON PERHALOGENANTES Y POSTERIOR HIDROLISIS. EL PROCEDIMIENTO ES UTIL PARA LA SINTESIS DE LOS COMPUESTOS HALOGENADOS INTERMEDIOS. LOS COMPUESTOS ASI OBTENIDOS, TIENEN IMPORTANTES APLICACIONES TERAPEUTICAS EN LAS ANGIOPATIAS ASOCIADAS A DIABETES MELLITUS.