Patent GB-1288984-A (GB)
IPC: C07D501/20
Filed: 1969-12-08
Abstract: 1288984 7-Aminocephalosporanic acid derivatives CIBA GEIGY AG 8 Dec 1969 [11 Dec 1968 23 April 1969 24 June 1969] 59714/69 Heading C2A 7-Aminocephalosporanic acid derivatives of the formula in which R 1  is a tetrazole residue bound through a nitrogen atom and R 2  represents a hydrogen atom, a free hydroxyl group or a hydroxyl group esterified by a carboxylic acid, in which the ester oxygen atoms may be replaced by sulphur atoms (with the exception of the acetoxy group). an unsubstituted or N-substituted carbamoyloxy group in which the oxygen atoms may be replaced by sulphur, or a quaternary amino group or a salt or an internal salt thereof may be prepared by (a) reacting a compound of the Formula II in which Z represents a halogenoacetyl radical, e.g. bromoacetyl and R 2  represents a hydrogen atom or a free or esterified hydroxyl group (in which the oxygen atoms of the ester group may be replaced by sulphur atoms) with tetrazole or (b) acylating a compound of Formula II in which Z represents a hydrogen atom and R 2  represents a hydrogen atom or a free or esterified hydroxyl group (in which the oxygen atoms of the ester group may be replaced by sulphur atoms), so as to introduce the group R 1 -CH 2 -CO; and a compound obtained according to (a) or (b) in which R 2  represents the acetoxy group is converted into a compound having instead of the acetoxy group, a hydrogen atom or a free hydroxyl group or an ester group other than the acetoxy group (in which the oxygen atoms may be replaced by sulphur atoms) or an unsubstituted or N-substituted carbamoyloxy group in which group the oxygen atoms may be replaced by sulphur atoms, or a quaternary amino group, and, if desired, a resulting compound is converted into a salt or an internal salt thereof or a resulting salt is converted into the free carboxylic acid. R 2  may be a C 1-5  alkanoyloxy group optionally substituted by halogen, e.g. Cl (such as formyloxy, propionyloxy, butyryloxy, pivaloyloxy, or chloracetoxy); a mono- or di-cyclic arylcarbonyloxy or arylthiocarbonyloxy, arylcarbonylthio or arylthiocarbonylthio group optionally substituted by one or more of C 1-5  alkyl, C 1-5  alkoxy, C 1-5  alkylmercapto, halogen or nitro (such as benzoylthio); a group of formula -O-CO-NH-R 3 , wherein R 3  represents a hydrogen atom or an aliphatic, aromatic, araliphatic or heterocyclic radical espectially a straight- or branch-chain C 1-5  alkyl optionally substituted by C 1-5  alkoxy or halogen, examples of R 3  being methyl, ethyl or #-chlorethyl; a thiocarbamoylthio group of formula wherein R 3  is as above defined and R 4  is a hydrogen atom or R 3 ; or a quaternary amino group in which the quaternary nitrogen atom forms part of an aromatic ring, e.g. a quinoline, isoquinoline, pyrimidine or an optionally substituted pyridine ring of formula wherein R 5  is hydrogen, C 1-5  alkyl, C 1-5  alkoxycarbonyl, carbamoyl, carboxyl or halogen. The salts may be ammonium, alkali metal (e.g. sodium or potassium) or alkaline earth metal (e.g. calcium) salts, or salts with organic bases, e.g. triethylamine, N-ethylpiperidine dibenzylamine, N - benzyl - # - phenethylamine, N,N<SP>1</SP> - dibenzylethylenediamine, ethanolamine, diisopropylamine, procaine or ephenamine. Pharmaceutical preparations, animal fodder and additives to animal fodder comprise the above 7-aminocephalosporanic acid derivatives, which are active against gram-negative and gram-positive bacteria, and a carrier. Pharmaceutical preparations may be administered enterally, topically or parenterally in the form of tablets, dragees, salves, creams, capsules, solutions, suspensions or emulsions.