Verfahren zur Herstellung von neuen Azinen

摘要

Novel compounds of formula 1 wherein R1 is hydrogen, an alkyl group having at most 6 carbon atoms, an alkenyl group having 3-6 carbon atoms, a cycloalkyl or cycloalkyl-alkyl group having at most 8 carbon atoms, a cycloalkenyl group having 4-8 carbon atoms, or the propargyl radical, R2 is an alkenyl group having 3-6 carbon atoms, a cyclopropyl group, a cycloalkenyl group having 4-8 carbon atoms, or the propargyl radical, and R3 and R4 each represent hydrogen or a C1- 4 alkyl radical, and, when R1 is hydrogen, salts thereof, are prepared (1) by heating, to effect ring closure, a compound of formula or a functional derivative with regard to one or both carboxyl functions, or a tautomeric form thereof, (2) when R3 is the same as R4, by reacting at a raised temperature a 2,5-dithiobiurea of formula III R1-NH-CS-NH-NH-CS-NH-R2 or a dibasic salt of a tautomeric form thereof, with at least double the molar amount of a reactive ester, with regard to the hydroxyl function, of an acid of formula R3-CH(OH)-COOH, or a functional derivative thereof with regard to the carboxyl function, (3) by heating a thiosemicarbazone of formula V or VI or a salt of a tautomeric form thereof, with at least the equimolar amount of a derivative of the hydroxy-alkanoic acid shown above, (4) when R1 is the same as R2, and R3 is the same as R4, by reacting a suitable thiazolidinedione or rhodanine with half the molar amount of a salt of hydrazine, (5) when R1 is not hydrogen, by reacting in the presence of an acid binding agent a compound of formula I in which R2 is hydrogen or has the meaning given above, and wherein at least one of R1 and R2 is hydrogen, with a reactive ester of a compound of formula R2-OH at least an equimolar amount of this compound being employed when only one of R1 and R2 is hydrogen, and at least double the equimolar amount being employed when R1 and R2 are both hydrogen, or (6) when R1 is not hydrogen, by reacting in the presence of an acid binding agent a compound of formula I in which R1 is hydrogen with at least an equimolar amount of a reactive ester of a compound R11-OH wherein R11 has the meaning given for R1 above with the exception of hydrogen. The 2,5-dithiobiureas of formula III may be prepared by treating an isothiocyanate with a thiosemicarbazide. The thiosemicarbazones of formula V or VI may be prepared by treating a rhodanine with a thiosemicarbazide. Therapeutic compositions having turnover inhibiting and antiviral activity, which may be administered orally, rectally, parenterally or topically, contain as active ingredient a compound of formula I above.