GB1415881A - Alpha-cyanamino-acetamido-cephalosporins and penicillins - Google Patents

Abstract

1415881 α-Cyanaminopenicillins and cephalosporins E R SQUIBB & SONS Inc 14 Nov 1972 [19 Nov 1971 (2)] 52604/72 Heading C2C [Also in Division C3] Novel (α - cyanamino)acetamido - penicillins and cephalosporins having the Formula (I) and salts thereof, wherein A is a 6-aminopenicillanic acid moiety of Formula (II) or a 7-aminocephalosporanic acid moiety of Formula (III) wherein R 1 is hydrogen, C 1 -C 8 alkyl, C 1 -C 8 alkenyl, saturated or unsaturated C 3 -C 7 cycloalkyl, cycloalkyl-alkyl, adamantyl, aralkyl, aryl or a 5- or 6-membered heterocyclic group containing up to two hetero atoms selected from S; O and N and which may be substituted by halo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy or phenyl and may be joined to the molecule by an alkylene group; R is hydrogen, C 1 -C 8 alkyl, aralkyl, tri - (C 1 -C 8 alkyl)silyl, a salt-forming ion or a group of formula -CH 2 -O-CO-R 2 in which R 2 is C 1 -C 8 alkyl, aryl or aralkyl; and X is hydrogen, hydroxy, C 1 -C 8 alkanoyloxy, aroyloxy, aralkanoyloxy, the radical of a nitrogenous base, a quaternary ammonium radical, or X and R together represent a chemical bond linking the associated carbon and oxygen to form a lactone ring, and wherein the cycloalkyl and aryl rings may be simply substituted (e.g. by one to three halogen, alkyl or alkoxy groups) are prepared by (i) reacting a corresponding (α-amino)acetamido-penicillin or' cephalosporin with dicyanogen or a cyanogen halide, (ii) reacting a corresponding (α-amino) acetamido-penicillin or cephalosporin with an N-cyano-2-pyridone, or (iii) reacting a corresponding (α-halo)acetamido-penicillin or cephalosporin with cyanamide or an alkali metal cyanamide. Reaction (i) is preferably carried out at low temperature in a reaction-inert solvent in the presence of an acid-binding agent, using cyanogen bromide or chloride as the reactant. The N-cyano-2-pyridone used in reaction (ii) isprepared by reacting 2-acetoacetamidopyridine with sodium nitrite at acidic pH, or by reacting the sodium salt of 2(1H)-pyridone with cyanogen bromide. The preferred conditions' in reaction (iii) consist of reacting sodium cyanamide with the α-chloro or α-bromo penicillin or cephalosporin. The compounds (I) may be used in disinfecting compositions together with an inert dry or aqueous carrier, or may be used in pharmaceutical compositions with a pharmaceutically acceptable vehicle or diluent.