6,9-bis aminosubstituted benzo/g/isoquinoline-5,10-diones, pharmaceutical preparations in which they are comprised and synthesis process thereof

摘要

In the present invention there are disclosed compounds of the general formula I in which the substituents have specific meanings. In the present invention there are also claimed pharmaceutical preparations containing as an active substance said substituted benzo-isoquinolinediones and that exhibit antitumor activity. When performing synthesis of those compounds first (a) pyridine-3,4-dicarboxylic anhydride is brought into reaction with 1,4-difluorobenzene in the presence of a Lewis acid under formation of a mixture of the compounds of the general formulae VIIa and VIIb, (b) the mixture of the compounds VIIa and VIIb is cycled in the presence of 30 percent fuming sulfuric acid at a temperature in the range of 130 to 150 degC under the formation of the compound of the general formula II, (c) fluorine atoms being present in the compound II are substituted by reaction with stoichiometric amount or a slight excess of the compound of the general formula R-Nhi2 in which the -NH- and -OH groups in R are optionally protected by suitable protecting groups and at a temperature in the range of O degC to the solvent boiling point, (d) protecting groups that may be present in R are optionally removed under the formation of the compounds of the general formula I and (e) the compounds of the general formula I are optionally transferred to salts and/or solvates or they can be split to isomers thereof.