ACIDES INDENYL-ACETIQUES ET PROCEDE POUR LES

1276600 Substituted 3-indenyl acetic acid acid derivatives MERCK & CO Inc 5 Aug 1970 [8 Aug 1969 1 May 1970] 37829/70 Heading C2C Novel compounds of the general Formula I: wherein Ar is aryl or heteroaryl; R 1 is hydrogen, alkyl or haloalkyl; R 2 hydrogen or alkyl; R 3 , R 4 , R 5 and R 6 each are hydrogen, alkyl, acyloxy, alkoxy, nitro, amino, acylamino, alkylamino dialkylamino, dialkylamino alkyl, sulphamoyl, alkylthio, mercapto, hydroxy, hydroxyl alkyl, alkyl sulphonyl, halogen, cyano, carboxyl, alkoxycarbonyl, carbamoyl, haloalkyl cycloalkyl or cycloalkoxyl; R 7 is alkyl sulphinyl or alkyl sulphonyl; R 8 is hydrogen, halogen, hydroxy, alkoxy, alkyl, haloalkyl and M is hydroxy, alkoxy, substituted alkoxy, amino, alkylamino, dialkylamino, N-morpholino, hydroxyalkylamino, polyhydroxyalkylamino, dialkylaminoalkylamino, aminoalkylamino or the group OMe, wherein Me is a cation and the alkyl and alkoxy all being C 1-5 radicals, may be prepared by oxidizing a compound I in which R 7 is alkylthio to sulphoxide and optionally oxidizing the sulphoxide to the sulphone and/or optionally forming metal salts, esters or amides and separating the isomers. The compound I in which R 7 is alkylthio may be prepared by condensing an aldehyde II with an indene III wherein R* is an alkyl thio group, and E is an esterifying group; which may in turn be prepared by reacting a halo acetate halo-CH(R 1 )- COOAlk with an indanone IV: to produce III directly or to produce a hydroxyl compound which may be dehydrated to form III. The compound IV may be prepared by cyclizing an acid Va or a reactive derivative thereof): which in turn may be prepared by hydrogenation of the α,#-unsaturated acid VI or by decarboxylation of a malonic acid ester VII: The α,#-unseturated acids VI may be formed by condensation of a substituted benzaldehyde with a substituted haloacetic acid ester, halo- CH(R 2 )COOE or acid anhydride. The malonic ester derivative VII may be prepared by condensing a substituted benzyl halide with a malonic ester R 2 CH(COOE) 2 . The substituted benzaldehyde may be prepared by bromination followed by hydrolysis of the appropriate substituted toluene or Friedel Crafts condensation of Cl 2 CHOCH 3 with the appropriate substituted benzene followed by hydrolysis. Pharmaceutical compositions of the compounds I show anti-inflammatory and analgesic activity when administered topically, orally, rectally or parenterally with the usual excipients.