Patent GB-1417201-A (GB)
Title: Acridone carboxylic acids and their derivatives and pharmaceutical uses thereof
IPC: C07D219/06
Filed: 1973-01-03
Abstract: 1417201 Acridone carboxylic acids and their derivatives and pharmaceutical uses thereof SYNTEX CORP 3 Jan 1973 [19 July 1972] 386/73 Heading C2C  The invention comprises compounds of formula and the pharmaceutically acceptable, non- toxic esters, amides and salts thereof; wherein each R is C 1-5  alkyl and each R<SP>1</SP> is C 1-5  alkyl; (C 3-5 ) cycloalkyl; -O-(C 1-5  alkyl); (C 3-5 ) cycloalkoxy; hydroxy; C 1-7  alkanoyloxy; trichloroacetoxy; 2 - chloropropionyloxy; halo; mercapto; C 1-5  alkylthio; -CF 3 ; or a group of formulas -CO-R<SP>3</SP>, -S(O) n -R<SP>4</SP> in which R is hydrogen, C 1-5  alkyl, or cycloalkyl; R<SP>3</SP> is H, C 1-5  alkyl; cycloalkyl; phenyl, substituted phenyl (in which the substituent is halo, C 1-5  alkyl, -O-(C 1-5  alkyl), -O-C 1-5  alkylthio, -CF 3 , or cyano); or a monocyclic 5 or 6-membered aromatic or heterocyclic ring, the hetero atoms in the rings being selected from N, O and S; n is 1 or 2; R<SP>4</SP> is C 1-5  alkyl when n is 1 and R<SP>4</SP> is C 1-5  alkyl, -OH, -N 2 , C 1-5  alkylamino, or di C 1-5 -alkyl amino when n is 2; provided that in Formula (B), when R<SP>1</SP> is an alkyl group then this group contains at least 2 carbon atoms. These compounds may be prepared by a process comprising the steps of: (1) condensing an oaminobenzoic acid or substituted derivative thereof with p-halobenzoic acid in the presence of copper powder with anhydrous potassium carbonate; or (2) condensing an o-halobenzoic acid with a p-aminobenzoic acid or substituted derivative thereof in the presence of copper powder with anhydrous potassium carbonate; or (3) condensing an excess of aminobenzene or substituted derivative thereof with 1,3-dicarboxy - 4 - halobenzene in the presence of copper powder with anhydrous potassium carbonate; and (4) cyclizing a product of Steps (1), (2), and (3) to give the corresponding N- and/or 7-substituted acridone-2-carboxylic acid; and (5) optionally cleaving a 7-methoxy substituted product of Step (4) to give the corresponding hydroxy compound and treating the latter with lower alkyl halide in the presence of base optionally followed by hydrolysis to give the corresponding alkoxy substituted compounds; and (6) optionally esterifying any hydroxy substituted compound; and (7) optionally N-alkylating a product of Step (4) with lower alkyl halide in the presence of base optionally followed by hydrolysis; and (8) oxidizing an alkylacridone- 2-carboxylic acid with chromic acid in acetic acid-acetic anhydride to give the corresponding alkanoylacridone-2-carboxylic acids; and (9) acylating an acridone-2-carboxylic acid ester optionally followed by hydrolysis to give the corresponding 7-acylacridone-2-carboxylic acid or the lower alkyl esters thereof; and (10) reducing the acyl substituted acridone-2- carboxylic acid ester of Step (9) optionally followed by hydrolysis to give acid or the alkyl ester thereof; or (11) treating an appropriate acyl substituted acridone-2-carboxylic ester of Step (9) with alkyl or cycloalkyl Grignard reagent optionally followed by hydrolysis to give the corresponding tertiary hydroxyalkylacridone-2-carboxylic acid or the alkyl ester thereof; or (12) oxidizing alkylthio substituted acridone-2-carboxylic acid or an alkyl ester thereof with a peracid optionally followed by hydrolysis to give the corresponding alkylsulphinylacridone-2-carboxylic acid or the alkyl esters thereof; or (13) oxidizing an alkylthio substituted acridone-2-carboxylic acid or an alkyl ester thereof with hydrogen peroxide optionally followed by hydrolysis to give the corresponding alkylsulphonylacridone-2-carboxylic acid or the alkyl esters thereof; or (14) treating an alkylthio substituted acridone-2-carboxylic acid ester with chlorine under acidic conditions optionally followed by hydrolysis to give the corresponding chlorosulphonylacridone-2-carboxylic acid or the alkyl esters thereof; and (15) treating a chlorosulphonyl substituted acridone-2-carboxylic acid with base to give the corresponding sulphoacridone- 2-carboxylic acid; or (16) treating a chlorosulphonylsubstituted acridone-2-carboxylic acid with ammonia, monoalkylamine, or dialkylamine to give the corresponding sulphamoyl-, monoalkylsulphamoyl-, and dialkylsulphamoylacridone-2-carboxylic acid; or (17) optionally converting a product of Steps (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (15) and (16) to its pharmaceutically acceptable, non-toxic esters, amides, and salts. In preparation 2, the intermediate 4-(2- carboxyphenylamino)-benzoic acid is obtained by the reaction of 4-bromobenzoic acid with oaminobenzoic acid. The invention also comprises a composition useful for inhibiting the effects of allergy which contains as an active ingredient a compound according to the invention in admixture with a pharmaceutically acceptable non-toxic carrier.