Patent GB-788264-A (GB)
Title: Benz (c) acridine compounds and methods for obtaining the same
Inventor: ELSLAGER EDWARD FAITH
Filed: 1955-12-14
Abstract: The invention comprises substituted benz(c) acridine compounds of the general formula: <FORM:0788264/IV (b)/1> and acid addition salts thereof, wherein R represents hydrogen or an alkyl or a hydroxyalkyl radical containing not more than 5 carbon atoms, or an acyl derivative of the latter radical having the formula -alkylene-O-Acyl (Acyl being an aliphatic carboxylic acid residue containing from 2 to 18 carbon atoms, X represents a divalent alkyl radical containing from 2 to 5 carbon atoms, and Z represents hydrogen, a halogen, or an alkyl or alkoxy radical containing 1 or 2 carbon atoms, and the preparation thereof by reacting a 7-[(b -hydroxyethyl)aminoalkylamino] benz(c)acridine of the general formula: <FORM:0788264/IV (b)/2> or an acid addition salt thereof, wherein X and Z have the above significance and R1 represents hydrogen or an alkyl or a hydroxyalkyl radical containing not more than 5 carbon atoms, with the required acylating agent, e.g. an acyl halide or acyl anhydride.  It is preferable that R and R1 each represent a lower alkyl radical.  The reaction temperature may be in excess of about 50 DEG  C., e.g. a temperature about 50 DEG  to 110 DEG  C. is preferred.  The benz (c) acridine compounds of the above general formula may also be prepared by dissolving the corresponding acid addition salts in a suitable solvent and neutralizing the solution with a base.  The preferred compounds of the invention are of the general formula: <FORM:0788264/IV (b)/3> wherein Z and Acyl have the above significance.  The acid addition salts may be derived from hydrochloric, hydrobromic, sulphuric, phosphoric, oxalic, sulphamic, acetic, lactic, tartaric gluconic, pamoic, citric, salicylic, 5,51-methylene-disalicylic, benzoic, 8-hydroxy-7-iodo-5-quinoline sulphonic, a cresotinic, a methylene di - o - cresotinic, naphthoic and 3 - hydroxy-2-naphthoic acids. Penicillin salts of the benz (c) acridines of the above general formula are also referred to, the penicillin salt of 7-{g -[ethyl-(b - palmitoyloxyethyl)amino]propylamino}-benz (c) acridine being a particularly useful compound.  A large number of benz (c) acridines of the above general formula are referred to and prepared in the examples in which Z represents hydrogen, bromine and chlorine and the methyl, methoxy and ethoxy radicals, X represents an alkylene chain containin 2, 3, 4 and 5 carbon atoms, R represents hydrogen, and the methyl, ethyl, propyl, butyl, amyl, b -hydroxyethyl, b -acetoxyethyl, b -isocaproyloxyethyl, b -palmityloxyethyl, b  - myristoyloxyethyl, b -succinyloxyethyl, g  - heptoyloxypropyl, d -stearyloxybutyl, d  - palmitoyloxybutyl, b -palmityloxyamyl, e -lauroyloxyamyl and e -succinyloxyamyl radicals, and Acyl represents the acetoxy, propionoxy, butyryloxy, valeryloxy, heptoyloxy, palmityloxy, stearyloxy, lauryloxy, myristoyloxy, caproyloxy, isocaproxyloxy, capronyloxy, pelargonyloxy, caprylyloxy and heptadecanoyloxy groups. Starting compounds. 7-[b -hydroxyethyl)aminoalkylamino]benz(c)acridines of the above general formula are prepared by reacting an o-chlorobenzoic acid with an a -naphthylamine to form an o - (a  - naphthylamino) benzoic acid, e.g. N-a -naphthylanthranilic acid, which is treated with phosphorus oxychloride to form the corresponding 7-chloro-benz(c)acridine, e.g. 7-chloro-benz(c)acridine itself, and then with the required hydroxyalkylaminoalkylamine.  In the examples 7 - {g  - [ethyl(b  - hydroxyethyl) amino]propylamino - benz(c)acridine is prepared by reacting phenol, 7-chlorobenz(c) acridine and g -[ethyl(b -hydroxyethyl)amino] propylamine and is converted into its dihydrochloride; 2 - methoxy - 7 - {g  - [ethyl(b -hydroxyethyl)amino]propylamino}benz(c)acridine dihydrochloride is prepared by reacting phenol, 7 - chloro - 2 - methoxybenz(c)acridine and g  - [ethyl(b  - hydroxyethyl)amino] propylamine, and is converted into its dihydrochloride; 7 - {g  - [bis(b  - hydroxyethyl)amino] propylamino} - 10 - chloro - benz(c)acridine is prepared by reacting phenol, 7,10-dichlorobenz(c)acridine and g  - [bis(b  - hydroxyethyl) amino]propylamine, and is converted into its dihydrochloride; 7 - {g  - [ethyl(b  - hydroxyethyl)amino]propylamino} - 10 - chloro - benz(c) acridine is prepared by reacting phenol, 7,10-dichlorobenz(c) acridine and g  - [ethyl(b  - hydroxyethyl)amino] - propylamine and is converted into its dihydrochloride; 7 - {g -[ethyl(b  - hydroxyethyl)amino]propylamino}-10 - methyl - benz(c)acridine is prepared by reacting phenol, 7-chloro-10-methyl-benz(c) acridine and g  - [ethyl(b  - hydroxyethyl) amino]propylamine and is converted to its dihydrochloride; and 7 - {e  - [ethyl(b  - hydroxyethyl)aminoethyl)amino]amylamino} benz(c) acridine is prepared by reacting phenol, 7-chloro - benz(c)acridine, and e  - ethyl - b -hydroxyethylamino)amylamine and is converted into its dihydrochloride.  Hydroxyalkylaminoalkylamines of the general formula: <FORM:0788264/IV (b)/4> wherein X and R1 have the above significance, are prepared by reacting N-(bromoalkyl)-phthalimide with the required hydroxyalkylamine and subjecting the resulting N-[hydroxyalkylaminoalkyl]phthalimide to acid hydrolysis.  In this way e -(ethyl-b -hydroxyethylamino) amylamine is prepared by reacting monoethylethanolamine and N - (e  - bromoamyl) - phthalimide to form N - [e  - (ethyl - b  - hydroxyethylamino)amyl]phthalimide which is then acid hydrolysed.  g -[ethyl-(b -hydroxyethyl)-amino]propylamine is similarly prepared from monoethylethanolamine and N-(g -bromopropyl)-phthalimide.  Specification 788,130 is referred to.