GB1278566A - Substituted bis-benzimidazoles and compositions containing them - Google Patents

Abstract

1278566 Bis-benzimidazoles MERCK & CO Inc 4 Aug 1970 [6 Aug 1969] 37620/70 Headings C2C and C2P. The invention comprises compounds of formula and their salts, wherein R 1 and R 4 are each H, alkyl, alkenyl, alkynyl (C 1-5 -alkoxy) alkyl, hydroxyalkyl, carboxyalkyl, carboxyalkoxyalkyl, alkanoyl, aroyl, cycloalkyl, aryl, substituted aryl, aralkyl or dialkylaminoalkyl; R 2 , R 3 are each H, C 1-5 alkyl, C 2-5 alkenyl or aryl; R 7 , R 8 are each H, C 1-5 alkyl, C 2-5 alkenyl, acyl, phosphate or sulphate; and R 5 , R 6 , R1 5 , R<SP>1</SP> 6 are each H, halogen, C 1-5 alkyl, C 2-5 alkenyl, amino, C 1-5 alkoxy, C 2-5 alkenyloxy, haloalkyl, C 1-5 alkylamino, di-(C 1-5 alkyl) amino, C 1-6 alkanoylamino, nitro, sulphamyl (possibly N- substituted), C 1-5 alkylsulphonamido, carbamyl (possibly N-substituted), C 2-6 alkoxycarbonylamino, cyano, C 1-6 alkanoyl, C 1-5 -alkylthio, -alkylsulphinyl or -alkylsulphonyl, mercapto, amidino, formyl, carboxyl or C 2-6 alkoxycarbonyl provided that (a) at least one of R 5 , R 6 , R<SP>1</SP> 5 , R<SP>1</SP> 6 is other than H, halogen, alkyl or alkoxy when R 2 , R 3 , R 7 , R 8 are each H and R 1 , R 4 are each H, alkyl, hydroxyalkyl or benzyl; (b) both R 6 and R1 6 may not be H, C 1-5 alkyl or C 1-5 alkoxy when all other Rs are H; (c) both R 6 and R<SP>1</SP> 6 may not be halogen when all other Rs are H. These compounds, as well as those defined in provisos (b) and (c), are prepared by reacting an appropriately substituted o-phenylenediamine with tartaric acid or a derivative thereof (this may be conducted in 2 stages where the substituents in each benzimidazole nucleus are not identical), except that the following compounds are prepared as indicated: (1) R 1 and/or R 4 are alkanoyl or aroyl, by reacting the compounds where R 1 and/or R 4 are H with an alkanoyl or aroyl halide or anhydride; (2) at least one of R 5 , R 6 , R<SP>1</SP> 5 , R<SP>1</SP> 6 is carbamyl or C 2-6 alkoxycarbonyl, by reacting the corresponding carboxylic acid group(s) with an ammonium hydroxide or an alcohol; (3) at least one of R 5 , R 6 , R1 5 , R<SP>1</SP> 6 is cyano, by dehydrating the corresponding amide; (4) at least one of R 5 , R 6 , R<SP>1</SP> 5 , R<SP>1</SP> 6 is C 1-6 alkanoylamino, by reacting the corresponding amine with alkanoic acid halide or anhydride; (5) R 7 and/or R 8 is acyl, phosphate or sulphate, by reacting the corresponding alcohol with an acid anhydride or chloride, P 2 O 5 or H 2 SO 4 , respectively. Intermediates prepared are 4,3-NH 2 (NO 2 )C 6 H 3 SO 2 NRME, 3,4-(NH 2 ) 2 C 6 H 3 SO 2 NR Me (R=H or Me), 3,4-NH 2 (NO 2 )C 6 H 2 SMe, 3,4-(NH 2 ) 2 C 6 H 2 SMe, 2,3 - dihydroxy - 3 - [5(6) - methoxy-2- benzimidazolyl]propionic acid, and 1,2-bis-(5-chlorocarboxyl-2-benzimidazolyl) ethane-1,2-diol. Therapeutic compositions having antiviral activity comprise compounds of the above formula, with the addition that proviso (a) does not apply; administration may be oral, parenteral, nasal or topical.