Patent GB-1320569-A (GB)
Title: 3-substituted picolinyl penicillins and cephalosporins
IPC: C07D501/20
Filed: 1970-06-09
Abstract: 1320569 Penicillins; cephalosporins E R SQUIBB & SONS Inc 9 June 1970 27914/70 Headings C2A and C2C The invention relates to penicillins and cephalosporins of Formula I wherein R is halogen; XR<SP>2</SP> wherein X is O or S, -N(R<SP>3</SP>)R<SP>4</SP>, -N(R4)Y or R<SP>2</SP> is H, C 2 -C 12  hydrocarbon carboxylic acid acyl, C 1 -C 5  alkyl phenyl, phenyl C 1 -C 5  alkyl, phenyl; R<SP>3</SP> and R<SP>4</SP> are H, C 1 -C 5  alkyl, C 4 -C 7  cyclo-alkyl, phenyl, phenyl C 1 -C 5  alkyl, C 1 -C 5  alkyl phenyl, one of R<SP>3</SP> and R<SP>4</SP> being other than aryl or R<SP>3</SP> and R<SP>4</SP> taken together constituting a heterocyclic ring having up to 6 C atoms; Y is C 2 -C 12  hydrocarbon carboxylic acid acyl or a sulphonyl group derived from an alkyl or aryl sulphonic acid of up to 12 C atoms; Z is H or NO 2 ; R<SP>1</SP> is H, C 1 -C 5  alkyl, C 4 -C 7  cycloalkyl, C 1 -C 5  alkoxy, phenyl, C 1 -C 5  alkylphenyl, C 1 -C 5  alkoxyphenyl or halophenyl and n is 1 to 3; R<SP>5</SP> may be wherein M is H or a pharmaceutically acceptable non-toxic cation; A is H, acyloxy derived from a hydrocarbon carboxylic acid of up to 12 C atoms, a quaternary NH 4  radical, NH 2 , C 1 -C 5  alkyl amino, di-(C 1 -C 5  alkyl) amino, phenyl C 1 -C 5  alkylamino, di-(phenyl-C 1 -C 5  alkyl) amino, heterocyclic tertiary amino, C 1 -C 5  alkylmercapto, phenylmercapto, phenyl C 1 -C 5  alkyl mercapto, thiouronium, C 1 -C 5  alkyl substituted thiouronium, phenyl substituted thiouronium, phenyl C 1 -C 5  alkyl substituted thiouronium, a monovalent C-O bond when taken together with M, or an anionic charge when A is a quatenary NH 4  radical. The compounds are prepared by coupling an amino compound of Formula XVII wherein R<SP>5</SP> is as previously described with a compound of Formula XVIII wherein R and R<SP>1</SP> and n have the above meaning and B is H, halogen, azide or p-nitrophenoxy. 3-Mercaptopicolinyl penicillins and cephalosporins of Formula I are prepared by coupling the above amino compound XVII with a cyclic anhydride of Formula XXX wherein R<SP>1</SP> and n have the above meaning. Compounds of Formula XXXVI are prepared by reacting amino compound XVII with a cyclic anhydride of Formula XXXV The preparation of the following intermediates is described: 6-methyl, 5-methyl, 6-benzyl, 6- methoxy, 4-methyl-5-phenyl, 6-phenylethyl, 5- cyclohexyl, 4-methyl, 5-cyclohexyl-4-methyl, 4-methoxy-6-methyl and 5-ethoxy derivatives of 2-hydroxymethyl-3-pyridinol hydrochloride; 3 - benzyloxy - 2 - hydroxymethyl - 6 - methyl pyridine; 3-benzyloxy, 3-hydroxy and 3-acetoxy derivatives of 6-methyl picolinic acid; 3- bromo- and 3-amino-6-butylpyridine; 2-hydroxymethyl - 6 - butyl - and 6 - butyl -, - 3- dibenzylaminopyridine; 6 - butyl - 3 - dibenzyl aminopicolinic acid; 3-amino, 3-bromo, 3-mercapto, 3-benzylmercapto, 3-acetylmercapto and 3-benzoyl-mercapto derivatives of 6-butylpicolinic acid; 6 - butyl - 3 - methylphenylaminopyridine and the 2-hydroxy-methyl derivative; 6 - butyl - 3 - methylphenylaminopicolinic acid; 3-amino-, 3-bromo- and 3-benzylamino-, -picolinic acid; 3-(o-nitrophenylsulphonylbenzylamino), 3-acetylamino, 3-benzoylamino, 3- benzenesulphonamido, 3-diethylamino, 3-phenylamino and 3-(4<SP>1</SP>-phenyl)amino derivatives of picolinic acid. The pencillins and cephalosporins of Formula I may be added to animal feeds, incorporated in pharmaceutical formulations, e.g. tablets, capsules or injections, or used as a general disinfectant dissolved or suspended in water Œ detergent.