Patent EA-001770-B1 (EA)
Title: Benzimidazole derivatives, their use for treatment of viral infections
Inventor: CHEMBERLAIN STANLEY DAWES
IPC: A61K31/7056
Filed: 1996-12-19
Abstract: 1. A compound of the formula (I):   wherein R<1> represents hydrogen, a halo atom, azido, -NR<8>R<9> where R<8> and R<9> are the same or different and are each independently selected from the group consisting of hydrogen, hydroxyl, C1-12 alkyl, for example, C1-6 alkyl (where the alkyl moiety is optionally substituted by one or more substituents selected from the group consisting of halo, amino, azido, hydroxy, cyano, NO2, NHR<10>, SO2R<10>, SR<10>, OR<10>, COR<10> and haloC1-6 alkyl where R<10> is C1-6 alkyl, C3-6 alkenyl, C2-6 alkynyl, or aryl), C2-8 alkenyl, C1-6 alkoxy, C3-7 cycloalkyl, C2-8 alkynyl, C3-7 cycloalkenyl, C3-7 cycloalkylC1-6 alkyl, aryl, arylC1-6 alkyl, heteroaryl, heteroarylC1-6 alkyl, heterocyclyl and heterocyclylC1-6 alkyl or R<8>R<9> together with the N atom to which they are attached form a 3,4,5 or 6 membered heterocyclic ring; -NHNR<11>R<12>, where R<11> and R<12> are the same or different and each represent hydrogen or C1-6 alkyl; -N=NC1-6 alkyl or -NHOC1-6 alkyl; R<2> represents hydrogen, halo atom; R<3> and R<4> are the same or different and each represent hydrogen, halogen or NO2; R<5> and R<6> are the same or different and each represent hydrogen or hydroxy; R<7> represents hydrogen, CH3, or CH2R<13>, wherein R<13> can be selected from hydroxy, halogen atom and OR<14> (wherein R<14> is hydrogen, C1-8 alkyl, aryl or arylC1-6 alkyl); with the proviso that when R<2> represents hydrogen, R<3> and R<4> each represent chloro-, R<5> and R<6> are erythrohydroxy group and R<7> represents CH2OH, then R<1> represents azido, -NR<8>R<9> where R<8> and R<9> are the same or different and are each independently selected from the group consisting of hydroxyl, C1-6 alkyl (where the alkyl moiety is optionally substituted by one or more substituents selected from the group consisting of amino, azido, NO2, NHR<10>, SO2R<10>, SR<10>, OR<10>, haloC1-6 alkyl where R<10> is determined above), C7-12 alkyl (where the alkyl moiety is optionally substituted by one or more substituents selected from the group consisting of halo, amino, azido, hydroxy, cyano, NO2, NHR<10>, SO2R<10>, SR<10>, OR<10>, COR<10> and haloC1-6 alkyl where R<10> is determined above), C1-6 alkoxy, C3-7 cycloalkenyl, heteroaryl, heteroarylC1-6 alkyl, or heterocyclyl; -NHNR<11>R<12> where R<11> and R<12> are as hereinbefore defined; -N=NC1-6 alkyl or -NHOC1-6 alkyl; moreover with proviso, when R<1>, R<2>, R<3> and R<4> are as defined above, and both R<5> and R<6> are hydroxy, then R<7> represents hydrogen, CH3, or CH2R<13>, wherein R<13> can be selected from hydroxy, and OR<14> (wherein R<14> is hydrogen, or C1-6 aryl); or a pharmaceutically acceptable derivative thereof. 2. A compound of formula (I) as claimed in Claim 1 wherein the sugar moiety is selected from the group consisting of:    3. A compound of formula (I) as claimed in Claim 1 or 2 wherein R<1> is -NR<8>R<9>, where R<8> and R<9> are the same or different and are selected from the group consisting of C1-6 alkyl or C3-7 cycloalkyl. 4. A compound of formula (I) as claimed in any of Claims 1-3, wherein R<2> is hydrogen or a halo atom. 5. A compound of formula (I) as claimed in any of Claims 1-4 wherein R<3> and R<4> are both a halo atom. 6. A compound of formula (I) as claimed in any of Claims 1-5 wherein R<1> is -NR<8>R<9> where R<8> is hydrogen and R<9> is C1-6 alkyl, R<2> is hydrogen or a halo atom, R<3> and R<4> are both a halo atom and the sugar moiety is selected from the group consisting of 3'-desoxy-L-ribofuranosyl, 5'-desoxy-L-ribofuranosyl and 2'-desoxy-L-ribofuranosyl or a pharmaceutically acceptable derivative thereof. 7. A compound of formula (I) selected from the group consisting of: 4-bromo-5,6-dichloro-2-isopropylamino-1-(beta-L-ribofuranosyl)1H-benzimidazole; 5,6-dichloro-1-(3-desoxy-beta-L-ribofuranosyl)-2-isopropylamino-1H-benzimidazole; 5,6-dichloro-1-(5-desoxy-beta-L-ribofuranosyl)-2-isopropylamino-1H-benzimidazole; 5,6-dichloro-1-(beta-L-erythrofuranosyl)-2-isopropylamino-1H-benzimidazole; 5,6-dichloro-2-isopropylamino-1-(beta-L-xylofuranosyl)-1H-benzimidazole; 1-(2-desoxy-beta-L-ribofuranosyl)-5,6-dichloro-2-isopropylamino-1H-benzimidazole; 2-isopropylamino-1-(beta-L-ribofuranosyl)-4,5,6-trichloro-1H-benzimidazole; 4-bromo-2-cyclopropylamino-5,6-dichloro-1-(beta-L-ribofuranosyl)-1H-benzimidazole; 2-cyclopropylamino-1-(beta-L-ribofuranosyl)-4,5,6-trichloro-1H-benzimidazole; 4,6-dichloro-2-isopropylamino-1-(beta-L-ribofuranosyl)-1H-benzimidazole; and 1-(beta-L-erythrofuranosyl)-2-isopropylamino-4,5,6-trichloro-1H-benzimidazole. 8. A pharmaceutical composition comprising a compound of formula (I) as claimed in any of Claims 1-7 and a pharmaceutically acceptable excipient therefor. 9. The use of a compound of formula (I) according to any of Claims 1-7 in medical therapeutics. 10. The use of a compound of formula (I) according to any of Claims 1-7 in preparation of drugs for the treatment or prophylactics of viral infections.