1-Aryl-2-N-, S- or O-substituted benzimidazole derivatives, their use for the production of pharmaceutical agents as well as pharmaceutical preparations that contain these derivatives

Benzimidazole derivatives with general formula I

• 8
• in which
• R1 stands for an aryl group or a five- or six-membered heteroaryl group with one or two heteroatoms, selected from the group that comprises N, S and O,
• whereby the aryl group or heteroaryl group with up to three radicals can be substituted independently of one another, selected from the group that comprises:
• F, Cl, Br, C(NH)NH2, C(NH)NHR4,
• C(NH)NR4R4′, C(NR4)NH2, C(NR4)NHR4′, C(NR4)NR4R4′,
• X—OH, X—OR4, X—OCOR4, X—OCONHR4,
• X—COR4, X—C(NOH)R4, X—CN, X—COOH, X—COOR4, X—CONH2,
• X—CONR4R4′, X—CONHR4,
• X—CONHOH, X—SR4, X—SOR4, X—SO2R4, SO2NH2, SO2NHR4,
• SO2NR4R4′, NO2, X—NH2,
• X—NHR4, X—NR4R4′, X—NHSO2R4, X—NR4SO2R4′, X—NHCOR4, X—NHCOOR4,
• X—NHCONHR4 and R4,
• whereby X is a bond, CH2, (CH2)2 or CH(CH3), and
• whereby also R4 and R4′, independently of one another, have the meanings that are further indicated below, and
• whereby two substituents at R1 in each case can be linked to one another in such a way that they jointly form a methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl group, if the substituents at R1 are in ortho-position to one another,
• Z stands for a grouping that is selected from the group that comprises NH, NR2′, O, S, SO and SO2, in which R2′ has the meaning that is indicated below,
• R2 and R2′ in each case stand for a radical that is selected from the group that comprises:
• C1-4-perfluoroalkyl, C1-6-alkyl, (C0-3-alkanediyl-C3-7 cycloalkyl), (C0-3-alkanediyl-aryl) and (C0-3-alkanediyl-heteroaryl),
• whereby the heteroaryl group is five- or six-membered and contains one or two heteroatoms, selected from the group that comprises N, S and O, and whereby R2 and R2′ are selected independently of one another,
• whereby the aryl and/or heteroaryl group in each case can be substituted with up to two radicals, selected from the group that comprises F, Cl, Br, CH3, C2H5, OH, OCH3, OC2H5, NO2, CF3, C2F5 and SO2NH2 and/or can carry an anellated methanediylbisoxy group and/or ethane-1,2-diylbisoxy group,
• whereby a ring member in the cycloalkyl ring can also be ring-N or ring-O if the cycloalkyl ring is five-membered, or one or two ring members in the cycloalkyl ring can be respectively ring-N and/or ring-O atoms if the cycloalkyl ring is six- or seven-membered,
• whereby the ring-N atoms also can be substituted with C1-3-alkyl or C1-3-alkanoyl, or if Z is NR2′, R2 and R2′ together with Z can form a five- to seven-membered heterocyclic ring, whereby the heterocyclic ring can be saturated and can contain another N, O or S atom, and can be substituted with a radical that is selected from the group that comprises C1-4-alkyl, (C0-3-alkanediyl-C1-3-alkoxy), C1-4-alkanoyl, C1-4-alkoxycarbonyl, aminocarbonyl and phenyl,
• R3 stands for one or two substituents that can be selected independently of one another, selected from the group that comprises:
• hydrogen, F, Cl, Br, OH, OR4, OCOR4, OCONHR4, COR4, CN, COOH, COOR4, CONH2, CONHR4, CONR4R4, CONHOH, CONHOR4, SR4, SOR4, SO2R4, SO2NH2, SO2NHR4, SO2NR4R4, NO2, NH2, NHR4, NR4R4, NHSO2R4, NR4SO2R4′, NHSO2R6, NR4SO2R6, NHCOR4, NHCOOR4, NHCONHR4 and R4, whereby radicals R4, R4′ and R6 are selected independently of one another and have the meanings that are further indicated below,
• A stands for a group that is selected from the group that comprises C1-10-alkanediyl, C2-10-alkenediyl, C2-10-alkinediyl and (C0-3-alkanediyl-C3-7-cycloalkanediyl-C0-3-alkanediyl),
• whereby a ring member in the cycloalkyl ring can be ring-N or ring-O if the cycloalkyl ring is five-membered, or one or two ring members in the cycloalkyl ring in each case can be ring-N and/or ring-O atoms if the cycloalkyl ring is six- or seven-membered, whereby the ring-N atoms can be substituted with at least one radical that is selected from the group that comprises C1-3-alkyl and C1-3-alkanoyl radicals,
• whereby in the aliphatic chains of the C1-10-alkanediyl, C2-10-alkenediyl, C2-10-alkinediyl and (C0-3-alkanediyl-C3-7-cycloalkanediyl-C0-3-alkanediyl) groups, a C atom can also be exchanged for O, NH, N—C1-3-alkyl or N—C1-3-alkanoyl and
• whereby at least one of the alkyl and cycloalkyl groups can be substituted with a radical that is selected from the group that comprises ═O, OH, O—C1-3-alkyl, NH2, NH—C1-3-alkyl, NH—C1-3-alkanoyl, N(C1-3-alkyl)2 and N(C1-3-alkyl)(C1-3-alkanoyl),
• B stands for a radical that is selected from the group that comprises COOH, COOR5, CONH2, CONHNH2, CONHR5, CONR5R5, CONHOH, CONHOR5 and tetrazolyl,
• whereby B is bonded to a C atom of group A,
• whereby radicals R5 and R5′ are selected independently of one another and have the meanings that are further indicated below,
• Y stands for a group that is selected from the group that comprises O, NH, NR4, NCOR4, NSO2R4 and NSO2R6,
• whereby radicals R4 and R6 have the meanings that are further indicated below,
• R4 and R4′ in each case stand for a radical that is selected from the group that comprises CF3, C2F5, C1-4-alkyl, C2-4-alkenyl, C2-3-alkinyl and (C0-3alkanediyl-C3-7-cycloalkyl),
• whereby a ring member in the cycloalkyl ring can be ring-N or ring-O if the cycloalkyl ring is five-membered, or one or two ring members in the cycloalkyl ring can be ring-N and/or ring-O atoms in each case if the cycloalkyl ring is six- or seven-membered, whereby the ring-N atoms can be substituted with C1-3-alkyl or C1-3-alkanoyl,
• R5 and R5′ in each case stand for a radical that is selected from the group that comprises C1-6-alkyl, C2-6-alkenyl, C2-6-alkinyl, whereby in at least one of radicals R5 and R5′, a C atom can be exchanged for O, S, SO, SO2, NH, N—C1-3-alkyl or N—C1-3-alkanoyl, also (C0-3-alkanediyl-C3-7-cycloalkyl),
• whereby a ring member in the cycloalkyl ring can be ring-N or ring-O if the cycloalkyl ring is five-membered, or one or two ring members in the cycloalkyl ring in each case can be one or two ring-N and/or ring-O atoms if the cycloalkyl ring is six- or seven-membered, whereby the ring-N atoms can be substituted with at least one radical that is selected from the group that comprises C1-3-alkyl radicals and
• C1-3-alkanoyl radicals, also (C0-3-alkanediyl-aryl) and (C0-3-alkanediyl-heteroaryl), whereby the heteroaryl group can be five- or six-membered and can contain one or two heteroatoms, selected from the group that comprises N, S and O,
• whereby at least one of the alkyl and cycloalkyl radicals of R5 and R5′ also can be substituted with up to two radicals, selected from the group that comprises CF3, C2F5, OH, O—C1-3-alkyl, NH2, NH—C1-3-alkyl, NH—C1-3-alkanoyl, N(C1-3-alkyl)2, N(C1-3-alkyl)(C1-3-alkanoyl), COOH, CONH2 and COO—C1-3-alkyl, and at least one of the aryl and heteroaryl groups of R5 and R5′ can be substituted with up to two radicals, selected from the group that comprises F, Cl, Br, CH3, C2H5, OH, OCH3, OC2H5, NO2, N(CH3)2, CF3, C2F5 and SO2NH2 and/or at least one of the alkyl, cycloalkyl, aryl and/or heteroaryl radicals of R5 and R5′ can carry an anellated methanediylbisoxy- or ethane-1,2-diylbisoxy group,
• or whereby R5 and R5′ together with the amide-N-atom of B can form a five- to seven-membered, saturated or unsaturated heterocyclic ring, which can contain another N or O or S atom, and which can be substituted with C1-4-alkyl, (C0-2-alkanediyl-C1-4-alkoxy), C1-4-alkoxycarbonyl, aminocarbonyl or aryl,
• R6 stands for a radical that is selected from the group that comprises (C0-3-alkanediyl-aryl) and (C0-3-alkanediyl-heteroaryl), whereby the heteroaryl group is five- or six-membered and contains one or two heteroatoms, selected from the group that comprises N, S and O, and whereby at least one of the aryl and heteroaryl groups can be substituted with up to two radicals in each case, selected from the group that comprises F, Cl, Br, CH3, C2H5, OH, OCH3, OC2H5, NO2, N(CH3)2, CF3, C2F5, and SO2NH2 or at least one of the aryl or heteroaryl groups can also carry an anellated methanediylbisoxy group or ethane-1,2-diylbisoxy group.