Patent GB-1191016-A (GB)
Title: Iodinated Carboxyacylamino-Benzoic Acids
IPC: C07D207/404
Filed: 1967-05-11
Abstract: 1,191,016. Iodinated carboxyacylaminobenzoic acids; 5-substituted-3-amino-and-nitrobenzoic acids. STERLING DRUG Inc. 11 May, 1967 [17 May, 1966], No. 57399/68. Divided out of 1,191,015. Heading C2C. The invention comprises compounds of the general formula wherein Y<SP>1</SP> is an alkylene bridge having from two to eight carbon atoms or such a group interrupted by from one to three non-adjacent oxygen or sulphur atoms; R is H, H 2 N, (lower alkanoyl)- NH, (lower alkanoyl)N(lower alkyl), (lower alkanoyl)N(hydroxy-lower alkyl), (lower alkoxylower alkanoyl)NH, (lower alkoxy-lower alkanoyl)N(lower alkyl), HOOC, (lower alkyl)- NHCO, HOOC-Y<SP>1</SP>-CO-NH, lower alkyl. OOC-Y<SP>1</SP>-CO-NH, HOOC-Y<SP>1</SP>-CO-N- (lower alkyl) or HOOC-Y<SP>1</SP>-CON(hydroxylower alkyl); R<SP>1</SP> is hydrogen, lower alkyl, or hydroxy-lower alkyl, and R<SP>11</SP> is hydrogen or lower alkyl, " lower alkyl " and " lower alkoxy " are groups containing from 1 to 4 carbon atoms and " lower alkanoyl" is a group containing from 1 to 6 carbon atoms, except that at least one of R and R<SP>1</SP> is other than hydrogen, and their pharmaceutically acceptable salts. The compounds may be prepared by the following methods: (a) when R<SP>1</SP> and R<SP>11</SP> are hydrogen and Y<SP>1</SP> = Y, Y being a C 2-6  alkylene group such that 2 or 3 carbon atoms separate the carbonyl groups or is a 1,3-propylene group having 2-4 carbon atoms and such that the 2-carbon atom is replaced by O, S, SO or SO 2 , by, alkaline hydrolysis of compounds of the general formula (b) when R<SP>1</SP> is hydrogen and R is H, (lower alkanoyl)N(lower alkyl), (lower alkoxy-lower alkanoyl)N(lower alkyl), -COOH, (lower alkyl)- NHCO- or HOOC-Y<SP>1</SP>-CON(lower alkyl), by reaction of a compound of the general formula with a compound of the formula wherein R<SP>11</SP> is alkyl, to give a product wherein R<SP>11</SP> is alkyl, and optionally hydrolysing this product to give a compound in which R<SP>11</SP> is hydrogen, (c) when Y<SP>1</SP> = Y and R is -NH 2 , (lower alkanoyl)NH or (lower alkoxy-lower alkanoyl)NH, by reacting 3-amino-5-nitrobenzoic acid with an anhydride of the general formula to give a compound of the general formula hydrolysing this compound to give a compound of the general formula hydrogenating this compound to give a compound of the general formula reacting this compound with KICl 2  to give a compound of the invention wherein R is -NH 2  and R<SP>1</SP> and R<SP>11</SP> are hydrogen, and optionally, acylating this compound with a lower alkanoic or lower alkoxy-lower alkanoic acid anhydride to give a compound of the invention wherein R is (lower alkanoyl)NH or (lower alkoxy-lower alkanoyl)NH and R<SP>1</SP> and R<SP>11</SP> are hydrogen; (d) where the groups in the 3- and 5-positions are identical, by reacting 3,5-diamino-2,4,6-triiodobenzoic acid with (i) a compound of the formula Cl-CO-Y<SP>1</SP>-COOR<SP>11</SP>, and optionally, hydrolysing the product, or (ii) an anhydride as defined under method (b) above to give a compound of the general formula and then hydrolysing this product; (e) when R<SP>1</SP> is lower alkyl or hydroxy-lower alkyl; (f) when Y<SP>1</SP> is an alkylene group interrupted by -SO- or -SO 2 -, by per-acid oxidation of the corresponding compounds containing an interrupting group -S-. The salts are obtained in conventional manner. The compounds of the invention in the form of their water-soluble salts are employed as X-ray contrast agents. Specification 1,191,015 is referred to.