SUBSTITUTED SALICYLIC ACID DERIVATIVES AND PROCESSES FOR THEIR PREPARATION

摘要

1,272,190. Salicylic acid derivatives. MERCK & CO. Inc. 18 June, 1970 [25 June, 1969; 20 April, 1970], No. 29667/70. Heading C2C. The invention comprises compounds of formula and their pharmaceutically acceptable salts and anhydrides (when R 1 is OH), wherein A is CH 2 or CO; Y is CH 2 , NH, N-alkyl, S or O; R 1 is OH, NH 2 , alkoxy, alkylamino, dialkylamino, dialkylaminoalkylamino, dialkylaminoalkoxy, hydroxyalkoxy, polyhydroxyalkoxy, alkoxyalkoxy, PhO (possibly substituted), alkanoylaminoalkoxy, hydrazino, morpholino, piperidino, anilino, hydroxyalkylamino or an N- attached naturally occurring aminoacid radical; R 2 is H, acyl, alkyl or alkoxycarbonyl; R 3 is H, alkyl, cycloalkyl, alkoxy, haloalkyl or halogen; and X is H, alkyl, OH, alkoxy, acyloxy, halogen, haloalkyl; NO 2 , NH 2 , alkylamino, dialkylamino, acylamino, SH, alkylmercapto, alkylsulphinyl, alkylsulphonyl, sulphanyl, aminosulphinyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, alkylmercaptoalkyl, acylaminomethyl, CN, CO 2 H, carboalkoxy, carbamyl, aryl, aralkyl, aryloxy, aralkoxy or acyl; and no alkyl, alkoxy or (acyclic) acyl radical contains more than 6 C atoms. In examples, these compounds are prepared by (1) carbonation of the corresponding phenol (a) with CO 2 + K 2 CO 3 , (2) esterification of the CO 2 H or OH function, as well as hydrolysis of the esters, (3) amidation of the esters, (4) salt formation, (5) reaction of a compound where X is CH 3 with N-bromosuccinimide, and optionally reacting the bromomethyl compound (as well as reacting a compound where X is Br) with an amine, or a metal alcoholate; thiolate, thiolacetate or cyanide; (6) hydrolysis of a CN compound to CONH 2 . Intermediates otherwise are ethers of the phenols (a), and methyl 2-acetory-5-(5-acetoxymethylthenoyl) benzoate. Pharmaceutical and veterinary compositions for oral, parenteral, rectal or topical administration, comprise compounds of the above formula, which have antiinflammatory, analgesic, antipyretic, diuretic, antifibrinolytic and hypoglycaemic activity.