2-(4-(2-BENZOXAZOLYL)PHENYL)ALKANOIC ACID DERIVATIVES

摘要

1352723 2-Phenyl-benzoxazoles MERCK & CO Inc 6 Sept 1971 [10 Sept 1970 22 July 1971] 41499/71 Heading C2C Novel compounds of Formula (I) and esters, amides and pharmaceutically acceptable salts of those compounds in which R 4 is carboxy, in which formula R1αis hydrogen, methyl or fluoro, Rαis hydrogen, methyl, ethyl, allyl, halomethyl or trihalomethyl or Rαand R1αtogether are alkylidene or R1αcan be a methylene linkage attached to the unsubstituted ortho position of the benzenoid ring, R 2 , R 3 , X and Y are hydrogen alkyl, trihaloalkyl, halo, mercapto, alkylthio, alkylsulphinyl, alkylsulphonyl, nitro, amino, alkylamino, dialkylamino, cyano, carboxy, C 1-6 acyl or dialkyl sulphamyl in which each said alkyl group has 1 to 5 C atoms and R 4 is CH 2 OH or COOH (with the proviso that R1α, Rα, R 2 , R 3 , X and Y are not all hydrogen) are prepared by reacting an alkyl phenyl benzoxazole of general Formula (II) in which Rαis hydrogen methyl, ethyl, allyl, halomethyl or trihalomethyl with N-bromo succinimide in refluxing carbon tetrachloride to produce the corresponding bromo-alkylphenyl benzoxazole, treating the latter with sodium cyanide in a suitable solvent to produce the corresponding cyanoalkyl phenyl benzoxazole and subjecting the latter to acid hydrolysis to form a compound of Formula (I) followed by optionally reducing, esterifying, amidating, or neutralizing the compound. Compounds of Formula (I) in which Rαand R1αare methylidene are prepared by reacting p-chlorocarbonyl atropamide with an o-amino phenol to produce the corresponding 4-(1-carboxamidovinyl)-21-hydroxy benzanilide, heating the latter at a temperature above its melting point to bring about ring closure to form a compound of general Formula (V) Compounds of general Formula (II) are prepared in a similar manner. Other methods of ring closure used to form compounds of Formula (I) include the oxime rearrangement. Compounds of Formula (I) may also be prepared from 2- phenylbenzoxazoles via the malonic ester or acid derivative, using the Friedel Crafts reaction, by oxidative procedures or fluorination in the phenyl ring. Compounds of Formula (I) are useful in the treatment of inflammations and also exhibit anti-pyretic and analgesic activity and form a pharmaceutical preparation, with a suitable carrier, which may be administered orally, parenterally, topically or rectally.