Patent ES-380931-A1 (ES)
Title: Substituted arylpyridinecarboxylic acids and their derivatives
IPC: C07D307/54
Filed: 1970-06-19
Abstract: The invention comprises compounds of formula wherein COX and OY are ortho to each other and [Ar] is any aromatic structure (optionally attached to the pyridine ring through a system containing conjugated double bonds), R is H, or one or more substituents which may be alkyl, alkenyl, halogen, haloalkyl, OH, alkoxy, acyloxy, NO 2 , NH 2 , alkylamino, dialkylamino, acyl. amino, HS, alkylthio, alkylsulphinyl, alkylsulphonyl, aminoalkyl, alkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, alkylthioalkyl, CN, CO 2 H, alkoxycarbonyl, CONH 2 , aryl, aralkyl, aryloxy, aralkoxy or acyl X is- OH, NH 2 , alkylamino, dialkylamino, cycloalkylamino, N-attached N-heterocyclo, alkoxy, aralkoxy, hydroxyalkoxy, alkoxyalkoxy, dialkylaminoalkoxy, PhO (possibly substituted), dialkylaminoalkyl, hydroxyalkylamino or OM, where M is a non-toxic cation Y is H, alkyl, alkenyl, aralkyl, aryl, acyl or alkoxycarbonyl and R1 is H or alkyl provided that in a 2- hydroxynicotinic acid R is not H when R1 is H or Me, but in that case R is not p-Me when R1 is H. In examples, the compounds are prepared by (1) forming the OY group by hydrolysis or alcoholysis of the corresponding chloro- or bromo-pyridines, hydrogenolysis of the compounds where Y is benzyl, reaction of the corresponding amino-pyridines with HNO 2 , or alkylation or acylation of the compounds where Y is H (2) forming the compounds where X is OH by hydrolysing a corresponding nitrile or ester, oxidizing a corresponding alkylpyridine, or reacting the alkali metal derivatives of the corresponding hydroxy-pyridines with CO 2 (the products may be converted to the salts or esters), (3) forming the amides by reacting the acid chlorides (X = Cl ) with the appropriate amine (4) oxidizing a 2-aryl-8-methoxyquinoline to give a 6-aryl-2-hydroxynicotinic acid (5) forming the pyridine ring from non-heterocyclic components, or e.g. by reacting 2-(5-p-chlorophenyl- 2-furyl) - 2 - ureidoacetonitrile (from 5 - pchlorophenylfurfural cyanohydrin, with urea) with HCl (giving 6-p-chlorophenyl-3-hydroxypicolinamide) (6) reducing an arylchloropyridinolcarboxylic acid to replace Cl by H (7) effecting standard interconversions of endproducts, e.g. by diazotizing an aminophenyl compound followed by hydrolysis, or reducing a nitrophenyl compound. Intermediates also prepared are ethyl aroylpyruvates 2 - arylacetoacetaldehydes 2-aryl- 3-dimethylaminoacroleins 5- and 6-aryl-3- picolines 6 - aryl - 3 - bromo - 2 - and 4- picolines 6-arylnicotines 3-amino-5- and 6- arylpyridines 3 - amino - 6 - aryl - 2 - chloropyridines 2,4 - dihydroxy - 6 - arylcopazolines 3-aroyl-6-arylpyridines and their oximes ethyl 2 - aryl - 5 - cyanoisonicotinates and their 6-chloro and 6-hydroxy derivatives 6-amino (or chloro) - 5 - aryl - 2 - hydroxynicotinonitriles 5- and 6-aryl-3-nitropyridines 6-arylcinchomeronic acids and their esters, anhydrides, imides and imide-monoimines 6-arylnicotinic acids and their esters, amides and N-oxides 5- and 6-arylquinolinic acids and their imides. . Pharmaceutical and veterinary compositions for oral, topical, parenteral or rectal administration comprise compounds of the above formula, which have anti-inflammatory, antipyretic, analgesic, diuretic, antifibrinolytic and hypoglycaemic activity.