Verfahren zur Herstellung von neuen Derivaten des Pyrimido-[4,5-d]pyrimidins

摘要

The invention comprises compounds of the general formula: wherein R1, R2 and R3, which may be the same or different, each signify a basic group NR4R5 (in which R4 signifies an alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, alkylaminoalkyl, aryl, aralkyl, or amino group and R5 signifies a hydrogen atom or an alkyl or hydroxyalkyl group or together with R4 and the nitrogen atom, a substituted or unsubstituted heterocyclic ring, which, if desired, can be interrupted by further hetero-atoms) or R1 and R2 may have the above meanings and R3 signifies an alkoxy, alkoxyalkoxy, alkylaminoalkoxy, or alkylthio group; their salts with non-toxic inorganic or organic acids; the preparation thereof by reacting a pyrimido-pyrimidine of the formula: (in which 1-3 of the groups Z1-Z3, which may be the same or different, represent a halogen atom, a quaternary ammonium mercapto, or alkylmercapto group and the remaining groups Z1-Z3, which may be the same or different, represent the basic group NR4R5, and Z3 may also signify a hydroxy, alkoxy, alkoxyalkoxy, alkylaminoalkoxy or alkylthio group) with one or more molecular proportions of one or more amines HNR4R5 or with an alkali metal derivative of an alkanol, alkoxyalkanol, alkylaminoalkanol or alkylmercaptan, (where Z3 signifies a halogen atom and R3 signifies an unsubstituted or substituted alkoxy or alkylthio group) and, if Z3 signifies a free hydroxyl group and a compound is to be obtained in which R3 signifies an unsubstituted or substituted alkoxy group or an alkylthio group, the free hydroxyl group is then converted into an alkoxy or alkylthio group; and pharamceutical compositions containing them. 2,7-Diamino- 4-hydroxy-pyrimido- [4,5-d]-pyrimidines are prepared from a 2,7-dialkylmercapto-4-hydroxy- [4,5-d]-pyrimidine and morpholine, piperidine, pyrrolidine, methylpiperazine, diethyl- and dibutylamines. 2,7-Diamino-4- mercapto-pyrimido- [4,5-d]-pyrimidines are prepared from 2,7-dimorpholino-, -dipiperidino- and -dipyrrolidino-4-chloro-pyrimidino- [4,5-d]-pyrimidines and thiourea. 2,7-Diamino- 4-chloro-pyrimido- [4,5-d]-pyrimidines are prepared by chlorination of the 4-hydroxy analogues. Pharmaceutical compositions comprise the pyrimido-[4,5-d] pyrimidines in association with a pharmaceutical carrier or diluent and may be formulated as powders, tablets, dragees, capsules, granules, suppositories, emulsions, suspensions, syrups or solutions suitable for oral, parenteral or rectal administration. The compounds are coronary-dilators and sedatives.