Patent GB-888965-A (GB)
Title: Improvements in or relating to diamidines
Inventor: BERG SAMUEL SIDNEY
IPC: C07C275/42
Filed: 1958-12-15
Abstract: The invention comprises diamidines of the formula <FORM:0888965/IV (b)/1> (wherein R is meta or para to the amidino group and is hydrogen or halogen or alkoxy of at most 4 carbon atoms, and R1 and R2 are hydrogen or alkyl of at most 4 carbon atoms) and acidaddition salts thereof; and their preparation by reacting a compound of the formula <FORM:0888965/IV (b)/2> (wherein A is a cyano group or an amidino or alkylated amidino group) or an acid-addition salt thereof with phosgene or 3,5-dimethylpyrazole-1-carbonamide and, where A is cyano, converting it to the required amidino group by known methods, and, where the amidino group is unsubstituted and an alkylated amidino group is required, alkylating the amidino group by known methods. In examples (1) m-aminobenzonitrile and phosgene give N,N1-di-(m-cyanophenyl)-urea, this with ethanol and hydrogen chloride gives the corresponding di-imino ether hydrochloride and this with ammonia gives 3,31-diamidinodiphenylurea, isolated as the dihydrochloride monohydrate; (2) the iminoether of (1) is heated with ammonium isethionate to give the product of (1) as the di-isethionate; (3) m-aminobenzamidine monohydrochloride and phosgene give the product of (1) as the dihydrochloride sesquihydrate; (4) 3,5-dimethylpyrazole-1-carbonamide replaces the phosgene of (3), the same product being obtained; (5) 3-amino-4-methoxy-benzonitrile and phosgene give N,N1-di - (3 - cyano - 6 - methoxyphenyl) - urea which is then treated by the method of (1) to give the corresponding di-amidine dihydrochloride monohydrate; (6) 4-chloro-3-nitro-benzonitrile is reduced to 3-amino-4-chloro-benzonitrile, this with phosgene gives N,N1-di-(6-chloro-3-cyanophenyl)-urea, and this by the method of (1) gives the corresponding di-amidine dihydrochloride monohydrate; and (7) the imino-ether of (1) with methylamine hydrochloride gives 3,31-di-(N-methylamidino)-diphenylurea dihydrochloride sesquihydrate, the corresponding N-ethyl- and N,N-dimethyl-compounds being similarly prepared and isolated as their dihydrobromide hydrates.  A list of further salt-forming acids including inorganic acids, organic carboxylic and sulphonic acids and 8-chlorotheophylline also is provided.  In the first Provisional Specification are described diamidines of the formula <FORM:0888965/IV (b)/3> wherein R is a substituent.ALSO:Pharmaceutical compositions comprise a diamidine of the formula <FORM:0888965/VI/1> wherein R is meta or para to the amidino group and is hydrogen or halogen or alkoxy of at most 4 carbon atoms, and R1 and R2 are hydrogen or alkyl of at most 4 carbon atoms) or an acid-addition salt thereof, and a pharmaceutical carrier. Solutions, suspensions, syrups, elixirs, emulsions, powders, tablets and capsules are referred to.  Examples describe injection solutions of 3,31-diamidinodiphenylurea dihydrochloride monohydrate or diisethionate in distilled water, one also containing chlorocresol.  Other salt-forming inorganic and organic acids, including 8-chlorotheophylline, also are referred to.  In the second Provisional Specification an injection solution of 3,31-di-(N-methylamidino)-diphenylurea dihydrochloride sesquihydrate in distilled water is also described.