GB1360759A - 3-oxy-iminomethyl cephalosporin compounds - Google Patents

Abstract

1360759 3-Oxyiminomethyl cephalosporins ELI LILLY & CO 4 Dec 1972 [23 Dec 1971] 55938/72 Heading C2A New 3-oxyiminomethyl cephalosporins of the formula wherein n is 0 or 1; R is H, C 1-8 alkanoyl, C 2-8 - chloro- or bromo-alkanoyl, azidoacetyl, cyanoacetyl, wherein each Q is H or Me and Ar denotes 2- or 3-thienyl, 2- or 3-furyl, 2- or 3- pyrrolyl, phenyl or phenyl substituted with Cl, Br, I, F, CF 3 , OH, C 1-3 alkyl, C 1-3 alkoxy, CN, or NO 2 (at least one substituent being in the m- or pposition in the ring), G-X-CH 2 -C(O)- where X is O or S and G is as Ar above or may be 4-pyridyl when X is S, Ar-CHB-C(O)- where Ar is as defined above and B denotes -NH 2 , -NH 3 <SP>+</SP>, an amino group protected with a benzyloxycarbonyl, a C 1-4 alkoxycarbonyl, cyclopentyloxycarbonyl, cyclohexyl oxycarbonyl, benzhydryloxycarbonyl, triphenylmethyl, 2,2,2-trichloroethoxy carbonyl, -SO 3 H, phthalimido, the enamine from methyl acetoacetate or acetyl acetone, or B is -OH or -OH protected by esterification with a C 1-6 alkanoic acid, -COOH or a -COOH group protected by esterification with a C 1-6 alkanol, or B is -N 3 , -CN, or -C(O)NH 2 , or R is 2- sydnone-3-C 1-3 alkanoyl or where m is 0, 1 or 2, 5-aminoadipoyl in which the amino group is optionally protected with a C 1-3 alkanoyl or C 1-3 chloroalkanoyl group and those aminoadipoyl groups in which the carboxy groups are protected with benzhydryl, 2,2,2- trichloroethyl, C 4-6 alkyl or nitrobenzyl; R<SP>1</SP> is H or R and R<SP>1</SP> together with the nitrogen atom to which they are attached denote -NH 3 <SP>+</SP>, a salt group with an acid having a pKa of less than 4, or a cyclic imide group from a C 3-12 hydrocarbon dicarboxylic acid; the group in which Z is (-CH 2 -) y when y is 1 or 2 or Z is -O-, or R and R<SP>1</SP> taken together with the nitrogen atom denotes R<SP>2</SP> is C 4-6 tert.-alkyl, C 5-7 tert.-alkenyl, C 5-7 tert.- alkynyl, benzyl, methoxybenzyl, nitrobenzyl, 2,2,2 - trichloroethyl, 3,5 - di - tert. - butyl - 4- hydroxybenzyl, acetoxymethyl, pivaloyloxymethyl, 2-iodoethyl, benzhydryl, phenacyl, trimethylsilyl, succinimidomethyl, phthalimidomethyl or hydrogen, and Y is H, C 1-6 alkyl, C 2-6 haloalkyl (halo = Cl or Br), C 6-12 aromatic hydrocarbon, C 4-7 cycloalkyl, C 1-3 alkylene-XC 1-3 alkyl where X is O or S, -CH 2 COOR<SP>3</SP> where R<SP>3</SP> is H or C 1-6 alkyl, or -CH 2 -CH 2 -N(CH 3 ) 2 are prepared by reacting the corresponding 3- formal cephalosporins of formula wherein R, R<SP>1</SP>, R<SP>2</SP> and n are as defined above, with hydroxylamine, an O-substituted-N-unsubstituted hydroxylamine of formula H 2 N-O-Y (where Y is as defined above) or a salt thereof. Salts with pharmaceutically acceptable anions may be prepared in the usual ways. Pharmaceutical compositions comprising the active compounds of the invention and conventional carriers and excipients may be used as therapeutic antibiotic compositions for oral or parenteral administration.