ANGIOGENESIS INHIBITING THIADIAZOLYL PYRIDAZINE DERIVATIVES.

摘要

THIS INVENTION CONCERNS COMPOUNDS OF FORMULA (FORMULA 1)THE N-OXIDE FORMS, THE PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALTS AND STEREOCHEMICALLY ISOMERIC FORMS THEREOF, WHEREIN R1 IS HYDROGEN, C1-6ALKYL, C1-6ALKYOXY, C1-6ALKYLTHIO, AMINO, MONO- OR DI(C1-6ALKYL)AMINO, AR1, AR1-NH-, C3-6CYCLOALKYL, HYDROXYMETHYL OR BENZYLOXYMETHYL; R2 AND R3 ARE HYDROGEN, OR TAKEN TOGETHER MAY FORM A BIVALENT RADICAL OF FORMULA -CH=CH-CH=CH-; R4, R5 AND R6 ARE EACH INDEPENDENTLY SELECTED FROM HYDROGEN, HALO, C1-6ALKYL, C1-6ALKYLOXY, TRIFLUOROMETHYL, NITRO, AMINO, CYANO, AZIDO, C1-6ALKYLOXYC1-6ALKYL, C1-6ALKYLTHIO, C1-6ALKYLOXYCARBONYL OR HET1; OR WHEN R4 AND R5 ARE ADJACENT TO EACH OTHER THEY MAY BE TAKEN TOGETHER TO FORM A RADICAL OF FORMULA -CH=CH-CH=CH-; A IS A BIVALENT RADICAL OF FORMULA NR7, NR7-ALK1-X-, NR7-ALK1-X-ALK2-, O-ALK1-X-, O-ALK1-X-ALK2- OR S-ALK1-X-; WHEREIN X IS A DIRECT BOND, -O-, -S-, C=O, -NR8- OR HET2; R7 IS HYDROGEN, C1-6ALKYL OR AR2METHYL; R8 IS HYDROGEN,C1-6ALKYL OR AR2METHYL; ALK1 IS C1-6ALKANEDIYL; ALK2 IS C1-4ALKANEDIYL; AR1 AND AR2 ARE OPTIONALLY SUBSTITUTED PHENYL; PHENYL; HET1 AND HET2 ARE OPTIONALLY SUBSTITUTED HETEROCYCLES; HAVING ANGIOGENESIS INHIBITING ACTIVITY; THEIR PREPARATION, COMPOSITIONS CONTAINING THEM AND THEIR USE AS A MEDICINE.