Patent GB-1271767-A (GB)
Title: Substituted arylpyridinecarboxylic acids and their derivatives
Inventor: SHEN T-Y
IPC: C07D307/54
Filed: 1970-06-18
Abstract: 1,271,767. Arylpyridinolcarboxylic acids, esters and amides. MERCK & CO. Inc. 18 June, 1970 [25 June, 1969; 20 April, 1970], No. 29537/70. Heading C2C. 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 R<SP>1</SP> is H or alkyl; provided that in a 2- hydroxynicotinic acid R is not H when R<SP>1</SP> is H or Me, but in that case R is not p-Me when R<SP>1</SP> 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.