GB1271930A - Substituted phenoxysalicylic acids and their derivatives - Google Patents

Abstract

1,271,930. Phenoxysalicylic acid compounds. MERCK & CO. Inc. 18 June, 1970 [25 June, 1969; 20 April, 1970], No. 29670/70. Heading C2C. The invention comprises compounds of formula wherein R is OH-and the non-toxic and pharmaceutically acceptable salts, and the anhydrides thereof-or R is NH 2 , alkoxy, alkylamino, dialkylamino, dialkylaminoalkyl, dialkylaminoalkylamino, anilino, dialkylaminoalkoxy, hydroxyalkoxy, polyhydroxyalkoxy, alkoxyalkoxy, phenylalkoxy, phenoxy (possibly substituted), hydrazino, morpholino, piperidino, pyrrolidino or hydroxyalkylamino; R 2 is H, acyl, alkyl or alkoxycarbonyl; R 3 is H, halogen, haloalkyl, alkyl, cycloalkyl or alkoxy; n is 1-5; and each X is halogen, alkyl, alkoxy, acyloxy, haloalkyl, NO 2 , NH 2 , alkylamino, dialkylamino, acylamino, SH, alkylthio, alkylsulphinyl, alkylsulphonyl, sulphamyl, aminosulphinyl, aminoalkyl, alkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, alkylthioalkyl, CN, alkoxycarbonyl, carbamyl, aryl, aralkyl, aryloxy or alkoxy, and when X is alkoxycarbonyl, R is alkoxy; the alkyl and alkoxy residues containing up to 6 C atoms. In examples, these compounds are prepared by (1) carbonation of the corresponding phenoxyphenols (obtained generally by splitting the phenoxyphenyl/methyl ethers); (2) etherification of compounds where R 2 (or X n ) is OH, and conversely splitting the ethers to OH; (3) esterification of compounds where R is OH and/or R 2 is H; (4) amide formation; (5) reduction or reductive methylation of compounds where X n is NO 2 ; (6) conversion of X n =Cl to CN, and this to CONH 2 or CH 2 NH 2 and CH 2 NMe 2 ; (7) formation of the ether link between the phenyl residues; (8) hydrogenolysis of X n = benzyloxy to OH; (9) acylation of X n = NH 2 ; (10) oxidation of X n = MeS to MeSO and MeSO 2 ; (11) conversion of X n =Me to BrCH 2 with N-bromosuccinimide, and BrCH 2 to AcOCH 2 , HOCH 2 , HSCH 2 , MeO or MeS; (12) salt formation. Intermediates otherwise prepared are p-(pacetoxyphenoxy) benzoic acid, p-(p-acetoxyphenoxy) benzotrifluoride, p - (p - hydroxyphenoxy) benzotrifluoride. Therapeutic compositions for oral, parenteral, rectal or topical administration comprise compounds of the above formula, which have antiinflammatory, and in some cases antipyretic, analgesic, diuretic, antifibrinolytic or hypoglycaemic activity.