IE40162B1 - Cephalosporin compounds - Google Patents

Abstract

1478055 Cephalosporins CARLO ERBA SpA 2 July 1974 [27 July 1973 9 Oct 1973 (2) 3 April 1974 (2)] 29308/74 Heading C2C The invention comprises compounds (I) wherein Z is a cyano, NH 2 NHCO- or -CONH 2 group or a group of formula -COOR, -COR, R 1 -SO 2 - or R 1 -W- wherein R is a hydrogen atom or a C 1-6 alkyl group, R 1 is a C 1 -C 6 alkyl group, an amino or hydroxy group or such a group salified with an alkali metal and W is an oxygen or a sulphur atom: A and A 1 , which may be the same or different, each represents a C 1-6 branched or straight chain saturated aliphatic hydrocarbyl group, which is unsubstituted or substituted by one or more substituents selected from: (a) hydroxy, (b) halogen, (c) cyano, (d) amino, (e) -COR or -COOR, wherein R is as defined above, (f) phenyl, which is unsubstituted or substituted by one or more substituents selected from hydroxy, halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, and -NR 2 wherein each of the R groups, which may be the same or different, is as defined above, or (g) a heteromonocyclic group having a five- or six-membered ring containing at least one double bond and at least one heteroatom selected from N, S and O, which ring is unsubstituted or substituted by one or more substituents selected from hydroxy, halogen, C 1-6 alkyl, mercapto, C 1-6 aliphatic acyl, -CH 2 CN, and -NR 2 , wherein each of the R groups, which may be the same or different, is as defined above; Y is -NH-, -S- or -O-; B represents a heteromonocyclic group having a five-membered ring containing at least one double bond and at least one heteroatom selected from N, S and O, which ring is unsubstituted or substituted by one or more substituents selected from: (a<SP>1</SP>) hydroxy, cyano, mercapto, C 1-6 alkoxy, halogen, C 1-6 aliphatic acyl or -CH 2 -CN; (b<SP>1</SP>) unsubstituted amino or amino substituted by one or two C 1 -C 6 aliphatic acyl groups; (c<SP>1</SP>) C 1-6 alkyl groups which are unsubstituted or substituted by one or more substituents selected from hydroxy and halogen; (d<SP>1</SP>) C 1-6 alkenyl groups which are unsubstituted or substituted by one or more substituents selected from hydroxy and halogen; (e<SP>1</SP>) -(CH 2 ) x1 Ph, wherein x 1 is zero or 1 and Ph is a phenyl group which is unsubstituted or substituted by one or more substituents selected from C 1-6 alkyl, C 1-6 alkoxy, hydroxy, halogen and -NR 2 , wherein each of the R groups, which may be the same or different, is as defined above; (f<SP>1</SP>) cycloaliphatic hydrocarbon radicals containing 4 to 7 ring carbon atoms, which ring is unsubstituted or substituted by one or more substituents selected from C 1-6 alkyl and C 1-6 alkoxy; (g<SP>1</SP>) -(CH 2 ) x2 NR 2 , wherein x 2 is zero, 1 or 2 and wherein each of the R groups, which may be the same or different, is as defined above, or the two R groups, taken together with, the nitrogen atom, represent a morpholino, pyridyl, or piperidino group; or (h<SP>1</SP>) -S-R 1 , -SO 2 -R 1 , wherein R 1 is as defined above, -S-CH 2 CN, wherein R and x 1 are as defined above, or -(S-CH 2 ) x1 -Py, wherein x 1 is as defined above and Py is a pyridyl radical; M is hydrogen or a non-toxic pharmaceutically or veterinarily acceptable cation, or a pharmaceutically or verterinarily acceptable salt of the said compounds which are bases, and their preparation by reacting a compound (IV) or a silyl ester thereof with an acid Z-A-S-A 1 -COOH (V) of a halide, anhydride, amide, azide, reactive ester or salt thereof; by reacting a compound (VI), where X is a halogen atom with a compound Z-A-SH (VII) or a salt thereof; by reacting a compound (VIII) with a compound Z-A-X (IX); or by reacting a compound (X) with a compound H-Y-B (XI) or a salt thereof and, if desired, converting a resulting compound into a pharmaceutically or veterinarily acceptable salt and/or converting a resulting salt to a free base and/or, if desired, resolving mixtures of isomers to single isomers. Pharmaceutical and veterinary compositions having anti-bacterial properties comprise compounds (I) and a suitable carrier or diluent therefor. 7 - [(Cyanomethylthio)acetamido]cephalosporanic acid is made by reacting cyanomethylmercaptoacetic acid with 7-aminocephalosporanic acid. Cyanomethylmercapto acetic - acid is made by reacting cyanomethyl chloride with mercaptoacetic acetic. Carboxamidomethylmercapto acetic - acid, (α - cyanobenzyl)mercapto acetic - acid, (α - carboxamidoethyl)mercapto acetic - acid, 2 - oxopropylmercapto acetic - acid, (α - cyanoethyl)mercapto acetic - acid and (α - carbethoxy - α - methyl)ethyl mercapto acetic-acid are produced similarly. # - Cyano - # - chloroethylmercapto acetic - acid is made by reacting α-chloroacrylonitrile with mercapto acetic-acid. α - Cyanobenzyl chloride is made by reacting benzylcyanide with bromine. [GB1478055A]