6-aminothiopenicillanic acid and thiopenicillins

摘要

The invention relates to 6-aminothiopenicillanic acid and thiopenicillins of formula Wherein R is or or wherein R1, R2 and R3 are each hydrogen, chloro, bromo, fluoro, iodo, nitro, sulphamyl, trifluoromethyl, alkyl, alkoxy, alkylthio, dialkylamino, alkanoylamino, alkanoyl, alkanoyloxy, alkylsulphonyl, phenyl or benzyl; R4 and R5 are each hydrogen, chloro, bromo, fluoro, iodo, nitro, alkoxy, phenoxy, benzyloxy, trifluoromethyl, alkanoylamino or alkyl; and R6, R7 and R8 are each hydrogen, chloro, bromo, fluoro, iodo, nitro, alkyl, alkoxy, phenyl, phenoxy, benzyloxy, alkylthio, dialkylamino, alkanoylamino, alkanoyl, alkylsulphonyl, cycloalkyl radicals having from 5 to 7 carbon atoms inclusive or cycloalkoxy radicals having from 5 to 7 carbon atoms inclusive; and non-toxic salts thereof. The aforesaid alkyl, alkoxy and alkanoyl groups have 1 to 10 carbon atoms. 6-Aminothiopenicillanic acid is produced by (a) enzymatic hydrolysis of benzylthiopenicillin or (b) converting the 3-carboxylic acid group of 6-aminopenicillanic acid in which the 6-amino group is protected, to a reactive acylating derivative such as the acid anhydride, reacting the acylating derivative with a source of sulfhydryl groups, e.g. sodium hydrogen sulphide and then removing the protective group. The thio-penicillins are produced by (a) acylation of 6-aminothio-penicillanic acid or (b) converting the 3-carboxylic acid group of the corresponding penicillin having its amino group protected, to a reactive acylating derivative and reacting said acylating derivative of penicillin with a source of sulfhydryl groups to obtain the desired thiopenicillin with protected amino group, and removing the protected amino group, and removing the protecting group. The reactive acylating derivative is an acid anhydride, mixed acid anhydride, acid chloride or azolide. Typical thiopenicillins are the 6-(a -aminophenylacetamido)-6-(a -aminonaphthylacetamido) - and 6-[a -amino-(2- or 3-thienyl) acetamido] thiopenicillanic acids. The thiopenicillins and their non-toxic salts may be incorporated into pharmaceutical compositions for oral and parenteral use, e.g. solutions, dispersions, emulsions, tablets and capsules. They may be used for the treatment of infectious diseases caused by Gram-positive bacteria in poultry and animals and may be used for the treatment of mastitis in cattle. They are used as nutritional supplements in animal feeds.ALSO:An animal or poultry feed contains, as nutritional supplement, a thiopenicillin of formula:- Wherein R is or or and R1, R2 and R3 are H, Cl, Br, F, I, NO2, sulphamyl, trifluoromethyl, alkyl, alkoxy, alkylthio, di-alkylamino, alkanoylamino, alkanoyl, alkanoyloxy, alkylsulphonyl, phenyl or benzyl; R4 and R5 is H, Cl, Br, F, I, NO2, alkoxy, phenoxy, benzyloxy, trifluoromethyl, alkanoylamino, or alkyl; and R6, R7 and R8 are H, Cl, Br, F, I, NO2, alkyl, alkoxy, phenyl, phenoxy, benzyloxy, alkylthio, di-alkylamino, alkanoylamino, alkanoyl, alkylsulphonyl, cycloalkyl of C5-7 or cycloalkoxy of C5-7, and non-toxic salts thereof. The aforesaid alkyl, alkoxy and alkanoyl groups have 1 to 10 carbon atoms. Typical thiopenicillins are 6-(a -aminophenylacetamido)-thiopenicillanic acid and 6 - [a -amino-2-thienylacetamido]-thiopenicillanic acid.