Patent GB-912011-A (GB)
Title: Pharmaceutical compositions comprising aromatic derivatives of glyoxal
Inventor: CAVALLINI GUIDO
IPC: A61K31/12
Filed: 1960-07-27
Abstract: Glyoxal derivatives of general formula <FORM:0912011/IV (b)/1> wherein X is oxygen, sulphur, sulphonyl, sulphinyl, methylene, ethylene, vinylene or a single valence bond and Y is a hydrogen or halogen atom, or a nitro, hydroxy or acetamido group, may be prepared (a) by oxidation of the corresponding acetyl derivatives with selenium dioxide or, preferably, (b) by reaction of the corresponding dichloroacetyl derivatives with an alkali, e.g. a metal alcoholate. By the preferred method, there are prepared (as hydrates) diphenyl-4-glyoxal, 4-phenoxyphenyl glyoxal, 4-benzylphenyl glyoxal, 4 - (b  - phenylethyl)-phenyl glyoxal, 4-stilbene glyoxal, 4-phenylthiophenyl glyoxal, 2-phenoxyphenyl glyoxal, 4 - phenylsulphinylphenyl glyoxal, 4 - phenylsulphonylphenyl glyoxal, 4-(p-chlorophenoxy)-phenyl glyoxal, and 4-(p-nitrophenoxy)-phenyl glyoxal, and, by method (a) above, there are prepared (as hydrates) 4-(p-hydroxyphenoxy)-phenyl glyoxal and 4-(p-acetamidophenoxy) phenyl glyoxal.  In some cases the hydrate is heated to form the free glyoxal.  The following preparations of various of the intermediates are also disclosed; (a) 4-dichloroacetyldiphenyl, 4-phenoxydichloroacetophenone and the corresponding 2-phenoxy-compound, 4-dichloroacetyldiphenylsulphoxide and 4-dichloroacetyldiphenylsulphone (by direct chlorination of the corresponding acetophenone derivative); (b) 4-dichloroacetyldiphenyl-methane and -ethane, 4-dichloroacetylstilbene, 4-dichloroacetyldiphenylsulphide and 4-dichloroacetyl-4chlorodiphenylether by the reaction of dichloroacetyl chloride on the appropriate compound in the presence of aluminium chloride; (c) 4-acetyldiphenylsulphone by oxidation of 4-phenylsulphinylacetophenone with excess hydrogen peroxide, and the latter compound by oxidation of 4-acetyldiphenylsulphide with the calculated amount of hydrogen peroxide; (d) 41-nitro-4-acetyldiphenyl ether by Friedel-Crafts condensation of 4-nitrodiphenyl ether with acetyl chloride; and (e) 41-acetamido-4-acetyldiphenyl ether by the reduction of 41-nitro-4-acetyldiphenyl ether followed by acetylation under standard conditions.  The preparation of alcoholates and bisulphite addition compounds of various of the compounds of the above general formula is also described.ALSO:Pharmaceutical compositions useful in the treatment of viral infections comprise a carrier and a glyoxal derivative of the general formula <FORM:0912011/VI/1> wherein X is oxygen or sulphur or a sulphonyl, sulphinyl, methylene, vinylene or ethylene radical or a single valency bond and Y is a hydrogen or halogen atom, a nitro group, a hydroxy group or an acetamido group or a hydrate, alcoholate or alkali metal bisulphite addition compound thereof.  The compositions may be in forms suitable for internal (preferably oral) administration p  e.g. a tablet or capsule, or externally, e.g. in an ointment or suppository such forms comprising conventional pharmaceutical excipients.  The preferred active compounds are those of formula <FORM:0912011/VI/2> e.g. 4-phenoxy phenyl glyoxal and p-diphenylglyoxal.