GB1398722A - Disbustistuted xanthone carboxylic acid compounds - Google Patents

Abstract

1398722 Disubstituted xanthone carboxylic acid compounds SYNTEX (USA) Inc 12 July 1972 [12 Jan 1972 5 June 1972] 32534/72 Heading C2C The invention comprises compounds of the formula and non-toxic esters, amides, and salts thereof; wherein, either the X groups are identical and selected from 1-hydroxy-(C 1 -C 5 ) alkyl and the (C 1 -C 5 ) alkyl, cycloalkyl, tetrahydrofuran-2-yl, tetrahydropyran - 2 - yl, tetrahydropyran - 4- yl and 4 - alkoxytetrahydropyran - 4 - yl ethers thereof and the carboxylic acyl esters thereof; and lower alkanoyl; or one X group is selected from (C 1 -C 5 ) alkyl, cycloalkyl, (C 1 - C 5 ) alkoxy and cycloalkoxy, and the other X group is selected from 1-hydroxy (C 1 -C 5 ) alkyl and the (C 1 -C 5 ) alkyl, cycloalkyl, tetrahydrofuran - 2 - yl, tetrahydropyran - 2 - yl, tetrahydropyran - 4 - yl and 4 - alkoxytetrahydropyran-4-yl ethers thereof and the carboxylic acyl esters thereof; and lower alkanoyl. They may be obtained by (1) oxidizing a 5,7-dialkylxanthone-2-carboxylic acid with chromic oxide in acetic acid-acetic anhydride to give the corresponding 5,7-dialkanoylxanthone-2-carboxylic acids; and (2) optionally reducing a product of step (1) to give the corresponding 5,7-bis-(1- hydroxyalkyl)-xanthone-2- carboxylic acids; or (3) acylating a 5- or 7-alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy-xanthene-2-carboxylic acid alkyl ester with alkanoyl chloride, oxidizing the acylated products, to those corresponding in the xanthone series, optionally followed by hydrolysis to give the corresponding 5- alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy-7- alkanoylxanthone - 2 - carboxylic acids or the alkyl esters thereof and 5-alkanoyl-7-alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy xanthone- 2-carboxylic acids or the alkyl esters thereof; and (4) optionally reducing an acylated product in the xanthene series of step (3) to give the corresponding 5-alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy - 7 - (1 - hydroxymethyl) - xanthene - 2 - carboxylic acid alkyl esters and the corresponding 5 - (1 - hydroxymethyl) - 7- alkylcycloalkyl-, alkoxy- or cycloalkoxyxanthene - 2 - carboxylic acid alkyl esters, acylating the latter, oxidizing the acylated product, and basc hydrolysing the oxidized products to give the corresponding 5-alkyl-, cycloalkyl, alkoxy- or cycloalkoxy-7-(1-hydroxymethyl) - xanthone - 2 - carboxylic acids and 5 - (1 - hydroxyalkyl) - 7 - alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy - xanthone - 2 - carboxylic acids; and (5) optionally esterifying a hydroxyalkyl product of steps (2) and (4) to give the corresponding acyloxyalkylxanthone-2-carboxylic acid; and (6) optionally etherifying a hydroxyalkyl product of steps (2) and (4) to give the corresponding etherified hydroxyalkylxanthone-2-carboxylic acid; and (7) optionally converting a product of steps (1), (2), (3), (4), (5) and (6) to a corresponding pharmaceutically acceptable, non-toxic ester, amide or salt. Examples are aiven for the production of the compounds. Pharmaceutical compositions comprise the compounds of the above formula which may be administered orally, topically, parenterally or by inhalation in conventional forms optionally together with other pharmaceutical agents. They are useful for inhibiting the effects of allergic reactions, also as smooth muscle relaxants and as vasodilators. The 5,7 - dialkyl - xanthone - 2 - carboxylic acids are prepared by condensing o,p-dialkylphenol with a 1,3-dicarboalkoxy-4-halobenzene, base hydrolysing the product thereof, and cyclizing the hydrolysed product. The starting compounds of step (3) are prepared by reducing a 5- or 7-alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy xanthone - 2 - carboxylic acid and esterifying the product thereof, said 5- or 7-alkyl-, cycloalkyl-, alkoxy- or cycloalkoxy-xanthone-2-carboxylic acid being optionally prepared by condensing a o- or p-alkyl-, cycloalkyl-, alkoxy- or cycloalkoxyphenol with a 1,3-dicarboalkoxy-4-halobenzene, base hydrolysing the product, and cyclizing the hydrolysed product.