Patent GB-1291994-A (GB)
Title: Anti-viral guanidine compounds
Inventor: SWALLOW DOUGLAS LINTIN
IPC: C07C335/20
Filed: 1969-10-24
Abstract: 1291994 Anti-virial guanidine compounds IMPERIAL CHEMICAL INDUSTRIES Ltd 25 Sept 1970 [24 Oct 1969] 52262/69 Heading C2C Novel compounds of the Formula I wherein either A is a direct bond, X and Y are imino radicals, R<SP>1</SP> and R<SP>3</SP> are each a hydrogen or halogen atom, an alkyl radical of 1 to 8 carbon atoms, or an alkoxy, alkoxycarbonyl or acylamino radical of 1 to 6 carbon atoms, and R<SP>2</SP> is a hydrogen atom, a straight- or branchedchain alkyl radical of up to 8 carbon atoms, a phenyl radical or a substituted phenyl radical bearing as substituent a halogen atom, a hydroxy radical, an alkoxy or acylamino radical of up to 6 carbon atoms or a dialkylamino radical wherein each alkyl radical is of 1 to 6 carbon atoms, but excluding N-p-chlorophenyl- 4 - (3 - isopropylguanidino) benzamidine and N - p - chlorophenyl - 3 - (3 - isopropylguanidino) benzamidine; or A is an imino radical, one of X and Y is an imino radical and the other is a sulphur atom, and R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> have the meanings stated above; but excluding 1-p-chlorophenyl - 3 - (p - thioureidophenyl) guanidine and 1 - p - chlorophenyl - 3 - (p - guanidinophenyl thiourea; or A, X and Y are imino radicals, and when the radical is in the meta-position, R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> have the meanings stated above: and when the radical is in the para-position, either R<SP>2</SP> is a hydrogen atom, a branched-chain alkyl radical of 4 to 8 carbon atoms, a straight-chain alkyl radical of 5 to 8 carbon atoms, a methyl, ethyl, n-propyl or phenyl radical, or. a substituted phenyl radical as defined above, and R<SP>1</SP> and R<SP>3</SP> have the meanings stated above; or R<SP>2</SP> is an isopropyl or n-butyl radical, and either R<SP>1</SP> has the meaning stated above and R<SP>3</SP> is a halogen atom, an alkyl radical of 1 to 8 carbon atoms, or an alkoxy, alkoxycarbonyl or acylamino radical of 1 to 6 carbon atoms, or R<SP>1</SP> is a fluorine or iodine atom, an alkyl radical of 2 to 8 carbon atoms or an alkoxy radical of 2 to 6 carbon atoms, and R<SP>3</SP> is a hydrogen atom; but excluding 1-pchlorophenyl - 3 - (p - guanidinophenyl) guanidine and 1 - phenyl - 3 - p - (3 - phenyl - guanidino) phenylguanidine; and the pharmaceutically acceptable acid addition salts thereof may be prepared by (a) for those compounds wherein Y is sulphur, the reaction of III wherein X is imino with an isocyanate R<SP>2</SP>NCS; (b) for compounds wherein X is a sulphur atom, the reaction of an amino compound IV wherein Y is imino, with an isocyanate of the Formula V (c) for compounds wherein both X and Y are imino, reaction of a thiourea I, wherein either A is a direct bond, X is imino and Y is sulphur or A is imino, at least one of X and Y is sulphur and the other if any of X and Y is imino, with ammonia in the presence of a catalyst; or (d) for compounds wherein either A is an imino radical and at least one of X and Y is imino or A is a direct bond and X and Y are imino, the reaction of ammonia with a compound VI wherein either A is an imino radical, at least one of X<SP>1</SP> and Y<SP>1</SP> is a radical = S#R<SP>4</SP>Z#, wherein Z is chlorine, bromine or iodine and R<SP>4</SP> is a C 1-4  alkyl radical or an aralkyl up to C 10 , the other of X<SP>1</SP> and Y<SP>1</SP>, if any, is imino or sulphur, or A is a direct bond, X<SP>1</SP> is imino and Y is a radical = S#R<SP>4</SP>Z. Compounds III may be prepared when A is a direct bond and X is imino by reacting an aniline derivative VII with a nitrobenzoyl halide, converting the anilide to an imino chloride with PCl 5  and POCl 3 , reacting the imino chloride with ammonia to give an amidine and catalytically reducing the nitro group to amino. When A and X are imino, III may be produced by reacting an isocyanate V with a nitroaniline, converting the thiourea formed to a guanidine using ammonia/mercuric oxide and reducing the nitro group to amino. Pharmaceutical compositions of the compounds I with the usually excipients show anti-virial activity when administered orally or by inhalation of a spray.