GB1300083A - New pencillin esters - Google Patents

Abstract

1300083 α-Amino-penicillin esters LOVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB 6 March 1970 [13 March 1969 18 July 1969] 13402/69 and 36407/69 Heading C2A Novel esters of 6-(α-amino-arylmethyl)-penicillins having the Formula I, II or III and salts thereof with non-toxic acids, wherein n is 0-5; R 1 to R 9 are each H, CF 3 , NO 2 , NH 2 , OH, halogen, mono- or di-alkylamino, alkanoylamino, alkyl, alkoxy, alkylthio, alkanoyl, alkylsulphonyl, C 5 -C 7 cycloalkyl or cycloalkoxy, aralkyl, aralkylthio or aralkyloxy, with the proviso that at least one of R 1 , R 2 and R 3 (in Formula I) is other than H; and R 2 with R 1 or R 3 , R 5 with R 4 or R 6 , and R 8 with R 7 or R 9 can complete a carbocyclic ring; B is -O-, -S- or -NH-; and A is an aliphatic, alicyclic, aromatic or heterocyclic radial which may be substituted, are prepared either (a) by acylating the corresponding ester of 6-amino-penicillanic acid or a reactive derivative thereof with the appropriate α-substitutedarylmethyl carboxylic acid or its acylating derivative and if required, converting the α-substituent to -NH 2 ; or (b) by esterifying a 6-(α- amino-arylmethyl) penicillanic acid, or its salt, with a compound of Formula (VIII): X<SP>1</SP>CH 2 OCO(CH 2 ) n A wherein n and A are as above and X<SP>1</SP> is halogen, C 1 -C 16 acyloxy, or alkyl- or arylsulphonyloxy. The α-amino group may be protected during the reactions or may be replaced by a group (e.g. azido, nitro or halogen) which is subsequently convertible to -NH 2 by a method which does not cause destruction of the ester linkage or the lactam ring. The reactive derivative of the 6- aminopenicillanic acid may contain an N-trialkylsilyl radical. Suitable acylating agents may be the acid halide, anhydride or mixed anhydride or the free acid may be used in the presence of a condensing agent. Any hydroxy groups present are preferably also protected prior to the preparative reaction. In a modification of process (b), an easily available 6-acylamino penicillanic acid is esterified, the 6-acyl group subsequently being split off and replaced by the α-aminoaryl-methyl group of the inventive compound. Pharmaceutical compositions comprise a penicillin ester of Formula I, II or III above or a non-toxic salt thereof together with a pharmaceutically acceptable solid or liquid diluent or carrier.