GB1481807A - Cepham-derivatives and preparation thereof - Google Patents

Abstract

1481807 Cephem derivatives PFIZER Inc 14 Oct 1974 [17 Oct 1973] 44350/74 Heading C2C The invention comprises compounds of the formula and the salts thereof, wherein T is a tetrazoyl group which is either wherein R is an acyl group of the formula A is H, CH 3 COO, l-methyl-tetrazolyl-5-thio or 2 - methyl - 1,3,4 - thiadiazolyl - 5 - thio; R 1 is H, (C 3 -C 6 ) alkanoyloxymethyl, 1 - (C 4 -C 7 ) alkanoyloxyethyl, CH 3 OCH 2 - or phthalidyl and Rll is the same as R 1 or is a tetrazolyl cephem nitrogen protecting group or precursor thereof and is selected from and wherein R 6 is (C 1 -C 3 ) alkyl or phenyl, R 7 is OH, CH 3 O, (C 2 -C 4 ) alkanoyloxy or benzyloxy, R 8 is H, OH, F, Cl, Br, I, CH 3 , CH 3 O, (C 2 -C 4 ) alkanoyloxy, phenyl or benzyloxy, R 9 and R 10 are each H or CH 3 and X is O or S; Ar is cyano, bromo, phenyl, mono- or disubstituted phenyl where each substituent is hydroxy, fluoro, chloro, bromo, amino, methoxy, or methyl, phenoxy, phenylthio, pyridylthio, thienyl, 2- methyl - 1,3,4 - thiadiazol - 5 - ylthio, 1 - tetrazolyl, (C 1 -C 12 ) alkyl, (C 2 -C 12 ) alkenyl, (C 3 - C,) cycloalkyl, (C 5 -C 8 ) cycloalkenyl, cycloheptatrienyl, 1,4 - cyclohexadienyl, 1 - amino (C 4 -C 7 ) cycloalkyl, 5 - methyl - 3 - phenyl - 4- isoxazolyl; 5 - methyl - 3 - (o - chlorophenyl)- 4 - isoxazolyl, 5 - methyl - 3 - (2,6 - dichlorophenyl) - 4 - isoxazolyl, 5 - methyl - 3 - (2- chloro - 6 - fluorophenyl) - 4 - isoxazolyl, 2- (C 1 -C 4 ) alkoxy-1-naphthyl, sydnonyl, furyl, pyridyl, thiazolyl, isothiazolyl, pyrimidinyl, triazolyl, imidazolyl, pyrazolyl, substituted phenoxy, substituted phenylthio, substituted pyridylthio, substituted thienyl, substituted furyl, substituted pyridyl, substituted tetrazolyl, substituted thiazolyl, substituted isothiazolyl, substituted pyrimidinyl, substituted triazolyl, substituted imidazolyl or substituted pyrazolyl, each substituted moiety being substituted by up to two of fluoro, chloro, bromo, hydroxy, hydroxymethyl, amino, N,N-di (C 1 - C 4 ) alkylamino, (C 1 -C 4 ) alkyl, aminomethyl, aminoethyl, (C 1 -C 4 ) alkoxy, (C 1 -C 4 ) alkylthio, 2-aminoethoxy and N-(C 1 -C 4 ) alkylamino, Q is hydrogen, hydroxy, azido, amino or carboxy ; n is an integer of 0 or 1; provided that when Ar is pyridylthio, phenoxy, phenylthio, 2 - methyl - 1,3,3 - thiadiazol - 5 - ylthio, bromo or cyano and n is 1, Q is hydrogen or carboxy. They may be obtained by (1) acylating a compound of Formula I wherein R is replaced by H with an acid halide, an activated ester or a mixed anhydride of a carboxylic acid, or a mixture of a carboxylic acid and a carbodiimide to give R as an acyl group of the above formula; and (2) reacting a compound of Formula I where T is replaced by -CONHR 2 wherein R 2 is selected from groups of Formulµ III and IV above, with a chlorinating agent to produce an imino chloride followed by reaction with an azide to form a tetrazolyl group, optionally replacing the R 2 group by treatment with a mixture of CF 3 COOH and anisole. Pharmaceutical compositions comprise the compounds of Formula I above as antibacterial agents together with a pharmaceutical carrier, and may be administered orally, e.g. by way of animal feed supplements, or parenterally.