Cephalosporin derivatives

A cephalosporin compound the formula (IV) ##STR133## or salt or ester thereof wherein:

• R.sup.1 is hydrogen, C.sub.1-6 alkyl optionally substituted by halo, hydroxy, C.sub.1-4 alkoxy, carboxy, amino, cyano, C.sub.1-6 alkanoylamino, phenyl or heteroaryl, or R.sup.1 is C.sub.2-6 alkenyl;
• Het is a 5- or 6-membered heterocyclic ring selected from a group of the formulae II-III:
• ##STR134## wherein A is CH or a nitrogen atom;
• B is oxygen, sulphur or a group NR.sup.4 ;
• one or two of D, E, F and G are nitrogen atoms and the remainder are CH groups:
• the ring Het being fused by any two adjacent carbon atoms to the benzene ring;
• and Het being bonded via a carbon atom to the --CH.sub.2 NR.sup.1 CO-- group;
• R.sup.2 is hydroxy or an in vivo hydrolysable ester thereof;
• R.sup.3 is ortho to R.sup.2 and is hydroxy or an in vivo hydrolysable ester thereof;
• R.sup.4 is hydrogen or hydroxy, or C.sub.1-6 alkoxy, phenoxy, C.sub.2-6 alkenyl or C.sub.1-6 alkyl, (any of these groups being optionally substituted by hydroxy, C.sub.1-6 alkoxy, cyano, amino, C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, carboxy, C.sub.1-6 alkoxycarbonyl, C.sub.1-6 alkanoyloxy, carbamoyl, C.sub.1-6 alkylcarbamoyl, di-C.sub.1-6 alkylcarbamoyl, C.sub.1-6 alkoxycarbonylamino, phenyl, phenylC.sub.1-6 alkyl, carboxyaminocarbonyl, C.sub.1-6 alkoxycarbonylaminocarbonyl, benzoyl or C.sub.3-8 cycloalkyl) or R.sup.4 is phenyl, C.sub.3-8 cycloalkyl, amino, C.sub.1-6 alkylamino or di-C.sub.1-6 alkylamino:
• wherein the fused Het-benzene ring system and/or any phenyl group is further optionally substituted by at least one substituent selected from C.sub.1-6 alkyl, halo, hydroxy, hydroxy C.sub.1-6 alkyl, cyano, trifluoromethyl, nitro, amino, C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, phenyl C.sub.1-6 alkylamino, C.sub.1-6 alkanoyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.1-6 alkanoyloxy, carbamoyl, C.sub.1-6 alkylcarbamoyl, di-C.sub.1-6 alkyl carbamoyl, carboxy, carboxy C.sub.1-6 alkyl, C.sub.1-6 alkoxycarbonylC.sub.1-6 alkyl, sulpho, sulphoC.sub.1-6 alkyl, sulphonamido, C.sub.1-6 alkylsulphonamido, C.sub.1-6 alkoxycarbonyl, C.sub.1-6 alkanoylamino, thioureido and amidino;
• X is sulphur or sulphinyl;
• R.sup.6 is hydrogen, methoxy or formamido;
• R.sup.5 is 2-aminothiazol-4-yl or 2-aminooxazol-4-yl each optionally substituted in the 5-position by fluorine, chlorine or bromine, or R.sup.5 is 5-aminoisothiazol-3-yl, 5-amino-1,2,4-thiadiazol-3-yl, 3-aminopyrazol-5-yl, 3-aminopyrazol-4-yl, 2-aminopyrimidin-5-yl, 2-aminopyrid-6-yl, 4-aminopyrimidin-2-yl, 2-amino-1,3,4-thiadiazol-5-yl or 5-amino-1-methyl-1,2,4-triazol-3-yl;
• R.sup.7 is of the formula =N.O.R.sup.8 (having the syn configuration about the double bond) wherein R.sup.8 is hydrogen, (1-6C)alkyl, (3-8C)cycloalkyl, (1-3C)alkyl(3-6C)cycloalkyl, (3-6)cycloalkyl(1-3C)alkyl, (3-6C)alkenyl optionally substituted by carboxy, (5-8C)cycloalkenyl, (3-6C)alkynyl, (2-5C)alkylcarbamoyl, phenylcarbamoyl, benzylcarbamoyl, (1-4C)alkylcarbamoyl(1-4C)alkyl, di-(1-4C)alkylcarbamoyl(1-4C)alkyl, (1-4C)haloalkylcarbamoyl(1-4C)alkyl, (1-3C)haloalkyl, (2-6C)hydroxyalkyl, (1-4C)alkoxy(2-4C)alkyl, (1-4C)alkylthio(2-4C)alkyl, (1-4C)alkanesulphinyl(1-4C)alkyl, (1-4C)alkanesulphonyl(1-4C)alkyl, (2-6C)aminoalkyl, (1-4C)alkylamino(1-6C)alkyl, (2-8C)dialkylamino(2-6C)alkyl, (1-5C)cyanoalkyl, 3-amino-3-carboxypropyl, 2-(amidinothio)ethyl, 2-(N-aminoamidinothio)ethyl, tetrahydropyran-2-yl, thietan-3-yl, 2-oxopyrrolidinyl, or 2-oxotetrahydrofuranyl, or R.sup.8 is of the formula V:
• --(CH.sub.2).sub.q --C(COOH).dbd.CR.sup.9 R.sup.10 V
• wherein q is one or two and R.sup.9 and R.sup.10 are independently hydrogen or C.sub.1-4 alkyl;
• or R.sup.8 is of the formula VI:
• --CR.sup.11 R.sup.12 --(CH.sub.2).sub.r --COR.sup.13 VI
• wherein r is 0-3, R.sup.11 is hydrogen, (1-3C)alkyl or methylthio, R.sup.12 is hydrogen (1-3C)alkyl, (3-7C)cycloalkyl, cyano, carboxy (2-5C)carboxyalkyl or methanesulphonylamino, or R.sup.11 and R.sup.12 are joined to form, together with the carbon to which they are attached, a (3-7C)carbocyclic ring, and R.sup.13 is hydroxy, amino, (1-4C)alkoxy, (1-4C) alkylamino or of the formula NHOR.sup.14 in which R.sup.14 is hydrogen or (1-4C)alkyl;
• or R.sup.7 may be of the formula =CH.R.sup.15 wherein R.sup.15 is hydrogen, halogen, (1-6C)alkyl, (3-7C)cycloalkyl, (2-6C)alkenyl, (3-7C)cycloalkenyl, phenyl or benzyl.