SK287527B6 - 1,2-Diarylbenzimidazoles and their pharmaceutical use - Google Patents

Abstract

Described are benzimidazoles of the general formula (I) and the use of benzimidazole derivatives for the production of pharmaceutical agents for the treatment and prophylaxis of diseases that are associated with microglia activation.

Description

The invention relates to novel benzimidazole derivatives and to the use of benzimidazole derivatives for the preparation of medicaments for the therapy and prophylaxis of diseases associated with the activation of microglia.

BACKGROUND OF THE INVENTION

Almost all degenerative diseases of the central nervous system are associated with chronic inflammation. The central step of the inflammatory process is the activation of mononuclear phagocytic cells, microglia. It occurs, for example, in Alzheimer's disease by senile plaques, in Kreuzfeld's Jacob disease by prion protein, and in ischemic attack by dead cells. Microglia may remain in the activated state for a prolonged period of time during which they produce and secrete various inflammatory factors, such as reactive oxygen or nitrogen intermediates, proteases, cytokines, complementary factors, and neurotoxins, and in turn cause neuronal dysfunction and degeneration.

Non-steroidal anti-inflammatory agents (COX II-inhibitors) have been described to date for possible therapy of nerve inflammation (McGeer, PL, Roger, Neurology 42: 447-449 (1992), Rogers, J. Kirby, LC, Hempleman, SR, Berry, DL McGeer, PL, Kaszniak, AW, Zalinski, J., Cofield, M., Mansukhani, L., Wilson, P., Kogan, F., Neurology 43, 1609-1611 (1993), Andersen, K., Launer Hoes, AW, Breteler, MMB, Hofman, A., Neurology 45, 1441-1445 (1995), Breitner, JCS, Gau, BA, Welsh, KA, Plassman, BL, McDonald, WM Helms, MJ, Anthony, JC: Neurology 44, 227-232 (1994); The Canadian Study of Health and Aging, Neurology 44, 2073-2079 (1994)), cytokine modulators (McGeer, PL, McGeer, EG,: Brain Research Rev. 21, 195-218 (1995), McGeer, EG, McGeer, PL: CNS Drugs 7, 214-228 (1997), Barone, FC, and Feuerstein, GZ: J. Cerebral Blood Flow and Metabolism 19, 819 -834 (1999)) and complement cascade inhibitors (Chen, S., Frederickson, RCA and Brunden, KR: No Agiol (1996); McGeer, E. G., McGeer, P.L .: Drugs 55, 739-746 (1998)). These agents inhibit the synthesis or effect of individual inflammatory factors. However, there is a need for compounds that inhibit the earlier stages of the inflammatory process, thereby avoiding the emergence or effect of many inflammatory factors.

SUMMARY OF THE INVENTION

This problem has been solved by the preparation of the benzimidazole derivatives of formula (I), their tautomeric or isomeric forms or salts.

where

R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group comprising nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl group may be independently substituted with up to three of the following substituents:

fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH ₂ , C ( NR ⁴ ) NHR ⁴ ', C (NR ⁴ ) NR ⁴ R ⁴ ', XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XCOOH, XCOOR ⁴ , XCONH ₂ , XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO ₂ NH ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ⁴ , NO ₂ , XNH ₂ , groups XNHR ^4, XNR ⁴ group R ^4, a group XNHSO2R ^4, XN (SO 2 R ⁴⁾ SO 2 R ^4, SO 2 R ⁴ XNR group ^4, group ⁴ XNHCOR, XNHCOOR group ^4, group XNHCONHR ^4, tetrahydro-2,5-dioxopyrrole-l 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-diyl D-2,7-dioxoisoindol-1-yl or R ⁴ , wherein the two substituents on R ¹ , when in ortho position to each other, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy , propane-1,3-diyl or butane-1,4-diyl,

R ² is a monocyclic or bicyclic C 6-10 -aryl group or a monocyclic or bicyclic 5-10-membered heteroaryl group having 1-4 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, said aryl or heteroaryl group being independently substituted with up to three of the following substituents: fluorine atom, chlorine atom, bromine atom, iodine atom, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCOOH, XCOOR ⁴ , XCONH2, XCONHR ⁴ , XCONR ⁴ R ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , SO2NR ⁴ R ⁴ , NO2, XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ , XN (SO 2 R ⁴⁾ SO 2 R ^4, Item pin XNR ⁴ SO ² R ⁴ , tetrahydro-2,5-dioxopyrol-1-yl, 2,5-dihydro-2,5-dioxopyrol-1-yl, 2,7-dihydro-2,7-dioxoisoindole- 1-yl or R ⁴ , wherein the two substituents on R ² , when in the ortho position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or a butane-1,4-diyl group,

R ³ is one or two substituents independently of one another: hydrogen, fluorine, chlorine, bromine, iodine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH2, SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO2, XNH2, group XNHR ⁴ group, XNR ⁴ R ^4, a group XNHSO2R ⁴ group, XNR ⁴ SO 2 R ⁴ ', XN (SO 2 R ⁴⁾ (SO ₂ R ^4'), the group XNHCOR ⁴ group XNHCOOR ⁴ group, XNHCONHR ^4, tetrahydro-2 , 5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl or R ⁴ , wherein two R ³ substituents when they are in each other ortho-position, they may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl,

R ⁴ and R ^4, independently of one another are C _{t. 4-} perfluoroalkyl, C 1-6 -alkyl; ₆ -alkyl, C _{2nd 6} -alkenyl, C _{2nd 6-} alkynyl, C ₃ . ₇ -cycloalkyl, (C _{first 3} alkyl) -C _{third 7} -cycloalkyl; _3- alkylC _6-10 -aryl, C _1-3 -alkyl-substituted 5-10-membered heteroaryl having 1-4 nitrogen, sulfur or oxygen atoms, C 1-4 -aryl or 5-10-membered heteroaryl having 1- 4 nitrogen, sulfur or oxygen atoms, wherein the aryl and heteroaryl groups may be substituted with one or two substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, CH ₃ group, C ₂ H ₅ group, NO ₂ group, an OCH ₃ group, an OC ₂ H ₅ group, a CF ₃ group or a C ₂ F _{5 group} , or may also carry a fused methanediylbisoxy group, or an ethane-1,2-diyl-bisoxy group, and may further be one member in the 5-membered cycloalkyl ring in the 6-membered or 7-membered cycloalkyl ring, one or two ring members may be a nitrogen and / or oxygen atom, wherein the ring nitrogen atoms may optionally be substituted with a C _1-3 -alkyl group but bo C _1-3 -alkanoyl,

R ⁵ and R ⁵ independently of one another are a C 1-6 -alkyl group, C ₂ . _6- alkenyl or C ₂ . _6- alkynyl, wherein the carbon atom may be replaced by oxygen, sulfur, SO, SO ₂ , NH, N-C _1-3 -alkyl or N-C _1-3 -alkanoyl,

C ₃ . ₇ -cycloalkyl-C ₀ . _{A 3-} alkyl group, wherein in the five-membered cycloalkyl ring one member of the ring may be a nitrogen or oxygen atom and in the six-membered or seven membered cycloalkyl ring the nitrogen and / or oxygen may be one or two membered, wherein the nitrogen atoms in the ring may be optionally substituted -alkyl or C 1-6 alkyl. _3- alkanoyl,

_Io _C6-aryl or a 5-10-membered heteroaryl with 1-4 heteroatoms from the group nitrogen, sulfur and oxygen, wherein the said alkyl, alkenyl and alkynyl may be substituted with one of said cycloalkyl, aryl or heteroaryl groups, wherein all of said alkyl and cycloalkyl groups may be substituted by up to two substituents selected from the group consisting of CF ₃ , C ₂ F ₅ , OH, O-C _1-3 -alkyl, NH ₂ , NH-C]. _3- alkyl, NH-C _1-3 -alkanoyl, N (C _1-3 -alkyl) ₂ , N (C _1-3 alkyl) (C _1-3 -alkanoyl), COOH, CONH ₂ , COO-C 1-7 _3- alkyl, and all said aryl and heteroaryl groups may be substituted by one or two substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, CH ₃ group, C ₂ H ₅ group, NO ₂ group, OCH group ₃ , OC ₂ H ₅ , CF ₃ and C ₂ F ₅ , or may also carry fused methanediylbisoxy or ethane-1,2-diylbisoxy, or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7 membered heterocycle which can contain a further oxygen, nitrogen or sulfur and is optionally substituted C ^ -alkyl, C ₁ _4 alkoxy-C _{0th 2-} alkyl, C 1-6 alkyl; _4- alkoxycarbonyl, aminocarbonyl or phenyl,

And a CMO-alkanediyl, C ₂ .i ₀ -alkéndiylová group, a C _{2nd 10} -alkíndiylová group, a ₍₀ C, 5-C ₃ alkanediyl-_7-cycloalkanediyl-C _0-.5 alkanediyl) wherein the five membered cycloalkyl ring may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members of a nitrogen and / or oxygen atom, wherein the ring nitrogen atoms may be optionally substituted with a C _1-3 -alkyl group or a C _1-3 -alkanoyl group, wherein in said aliphatic chains one or two carbon atoms may be replaced by an oxygen atom, NH, N-C _1-3 -alkyl or NC 1. _{The 3-} alkanoyl, and alkyl or cycloalkyl groups may be substituted with up to two substituents from the group consisting of = O, OH, OC]. _3- alkyl, NH ₂ groups, NH-C ₁ groups. _3- alkyl, NH-C _1-3 -alkanoyl, N (C _1-3 alkyl) ₂ and N (C _1-3 alkyl) (C _1-3 alkanoyl) groups,

B is COOH, COOR ⁵ , CONH2, CONHNH2, CONHR ⁵ , CONR ⁵ R ⁵ ', CONHOH, CONHOR ⁵ , SO 3 H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO ₂ NR ⁵ R ⁵ , PO 3 OH, PO (OH) (OR ⁵ ), PO (OR ⁵ ) (OR ⁵ ), PO (OH) (NHR ⁵ ), PO (NHR ⁵ ) (NHR ⁵ ) or tetrazolyl group, each of which is attached to each carbon atom of A, or an array of YAB is N (SO 2 R ⁴⁾ (SO 2 R ⁴⁾ group or NHSO ₂ R ^4,

X is a bond, CH ₂ , (CH ₂ ) ₂ , CH (CH ₃ ), (CH ₂ ) ₃ , CH (CH ₂ CH ₃ ), CH (CH ₃ ) CH ₂ , CH ₂ CH (CH _3),

Y is O, NH, NR ⁴ , NCOR ⁴ , NSO ₂ R ⁴ , provided that when Y is NH, NR ⁴ , NCOR ^4, or NSO ₂ R ⁴ , and

(a) R ² contains a nitrogen-containing saturated heterocycle which is not substituted on the imine nitrogen atom by a hydrogen atom, a methyl group, an ethyl group, a propyl group or an isopropyl group, or

b) in the XNHR ⁴ or XNR ⁴ R ^4, optionally present in the substituent R ² is R ⁴ and / or R ⁴ C _M alkyl group, at the same time that B is COOH, SO ₃ H, PO ₃ H group ₂ or a tetrazolyl group and R ¹ and R ² are independently C 5-6-heteroaryl, or phenyl, where these are independently unsubstituted, once substituted by Ci_6-alkyl, Ci_4-perfluoroalkyl, O-C ^ -alkyl, O-C 1-4 -fluoroalkyl, COOH, COO-C 1-4 -alkyl, CO-C 1-6 -alkyl, CONH 2, CONHR ⁴ , NO ₂ , NH ₂ , NHCOR ⁴ , NHSO ₂ R ^4, or one or two halogen atoms from fluorine, chlorine, bromine and iodine, and the following compounds are excluded: [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -acetic acid methyl ester , 5 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester, 4 - [(1, 2-diphenyl-1H-benzimidazol-6-yl) oxy] -butanoic acid 5 - [[1- (4-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, 6 - [[1- (4-Nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 5 - [[1- (4-aminophenyl) -2-phenyl-1H-methyl] -methyl- benzimidazol-6-yl] oxy] pentanoic acid, 5 - [[1- [4 - [[(4-chlorophenyl) sulfonyl] amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester , 5 - [[1- [4 - [(acetyl) amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, 5 - [[1- (3-nitrophenyl) - 2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid, 6 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methyl ester 5 - [[1- (3-Aminophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester 5 - [[1- [3 - [[(4-chlorophenyl) sulfonyl] [amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid, 5 - [[1- [3 - [(acetyl) amino] phenyl] -2-phenyl-1H-benzimidazole-, methyl ester 6-yl] oxy] pentanes ej.

Physiologically acceptable salts can be formed with inorganic and organic acids such as oxalic acid, lactic acid, citric acid, fumaric acid, acetic acid, maleic acid, tartaric acid, phosphoric acid, hydrochloric acid, hydrobromic acid, sulfuric acid, acid toluenesulfonic acid or methanesulfonic acid.

Inorganic and organic bases which form physiologically acceptable salts such as alkali hydroxides such as sodium or potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, ammonia, amines such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine are suitable for the preparation of salts of acid groups. or tris (hydroxymethyl) methylamine.

The term "aryl" refers in particular to an optionally substituted phenyl, biphenyl, naphthyl, indane or fluorenyl group.

The heteroaryl group consists of 5-10 basic backbone atoms and may contain 1-4 heteroatoms. The heteroatoms are an oxygen atom (O), a nitrogen atom (N) and a sulfur atom (S). Examples of monocyclic heteroaryl groups are pyrrolyl, thienyl, furanyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, furazanyl, pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl. Examples of bicyclic heteroaryl groups are thienoimidazolyl group, indolyl group, isoindolyl group, benzothiophenyl group, benzofuranyl group, benzimidazolyl group, indazolyl group, imidazopyridinyl group, purinyl group, quinolyl group, isoquinolyl group, phazolazinyl group, quinazinyl group, quinazinyl group, quinazinyl group, quinazinyl group, quinazinyl group, quinazinyl group, quinazinyl group naphthyridinyl and pteridinyl. When aryl or heteroaryl groups are part of the substituent R ¹ , the bond to the nitrogen atom in the benzimidazole proceeds via a carbon atom.

The alkyl groups may be unbranched or branched. Examples are methyl, ethyl, propyl, isopropyl, n-butyl, n-butyl, tert-butyl, n-pentyl, sec-pentyl, tert-pentyl, neopentyl, n-hexyl a group, a sec-hexyl group, a heptyl group, an octyl group or a nonyl group.

CF ₃ and C ₂ F ₅ are preferred as perfluorinated alkyl groups, and formyl, acetyl or propionyl are preferred as alkanoyl groups.

Alkenyl groups may be unbranched or branched. By way of example, the following may be mentioned: vinyl, 2-propenyl, 1-propenyl, 2-butenyl, 1-butenyl, 1-methyl-1-propenyl, 2-methyl-2-propenyl or 3- methyl-2-propenyl group.

The alkynyl groups may be unbranched or branched. Examples which may be mentioned are ethynyl, 1-propynyl, 2-propynyl, 1-butynyl or 2-butynyl.

Cycloalkyl groups mean cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

The saturated heterocycle or cycloalkyl group having one or more heteroatoms may be, for example, piperidine, pyrrolidine, tetrahydrofuran, morpholine, piperazine, hexahydroazepine or 2,6-dimethylmorpholine, N-phenylpiperazine, methoxymethylpyrrolidine, the ring being adjacent to the carbon atom, it may be carried out through optionally present nitrogen atoms in the ring.

Examples of alkanes, alkenes and alkynes for A may be the following groups: a straight or branched alkylene group containing 1-8 carbon atoms such as methylene, ethylene, propylene, butylene, pentylene, etc., 1-methylethylene , 1-ethyl-ethylene, 1-methyl-propylene, 2-methyl-propylene, 1-methyl-butylene, 2-methyl-butylene, 1-ethyl-butylene, 2-ethyl-butylene, 1-methyl-pentylene, 2-methyl-pentylene, 3-methyl-pentylene etc.

Unbranched or branched alkenylene and alkynylene groups containing 2-8 carbon atoms are alkenylene groups, respectively. alkynylene groups with double and triple bonds at all possible positions, as well as with methyl or ethyl substituents at all possible positions. In these groups, one or two carbon atoms may be replaced by an oxygen atom, an NH group, a N-C _1-3 -alkyl group or an NC _{b 3} -alkanoyl group, the exchanged group being separated by at least two carbon atoms from Y.

If the two residues are in the ortho-position, they can form a common ring with the adjacent aroma. Compounds in which nitrogen, oxygen or sulfur atoms bind to olefinic or acetylenic multiple bonds, or in which several nitrogen, oxygen, sulfur or halogen atoms are bonded to the same aliphatic carbon atom, or in which nitrogen, oxygen or sulfur atoms together they are excluded unless these linkages are explicitly defined, for example, in the functional groups or heteroaromatics enumerated in the claims.

Preferred are benzimidazoles wherein

R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-2 heteroatoms selected from the group comprising nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine, chlorine, bromine, ΧΟΗ, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ ', XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO 2, XNHR ⁴ , XNR ⁴ R ⁴ or R ⁴ , with two substituents on R ¹ when in ortho position to each other, they may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1 , 4-diyl.

Also preferred are benzimidazoles in which

R ² is a monocyclic or bicyclic C 6-10 -aryl group or a mono- or bicyclic 5-10-membered heteroaryl group with 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl the group may be independently substituted with up to three of the following substituents: fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCOOH, XCOOR ⁴ , XCONH2, XCONHR ⁴ , XCONR ⁴ R ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , a group XSR ^4, group XSOR ^4, group XSO2R ^4, the group SO 2 NH _2, SO ₂ NHR ^4, a group SO 2 NR ⁴ R ⁴ ', NO 2, XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ^4, XN ( SO 2 R ⁴⁾ SO 2 R ^4, SO 2 R ⁴ group XNR ⁴ al or a group R ⁴ , wherein the two substituents on R ² , when in the ortho position, can be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane- 1,4-diyl.

Also preferred are the benzimidazoles of formula (I) wherein

R ³ is one or two substituents independently of one another: hydrogen, fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO ₂ NH ₂ , SO2NHR ⁴ , SO2NR ⁴ R ⁴ ', NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO ₂ R ⁴ , XNR ⁴ SO2R ⁴ ', XN (SO2R ⁴ ) SO ₂ R ⁴ ', XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ or R ⁴ , wherein the two R ³ substituents, when in ortho position to each other, may be joined together to form together methanediylbisoxy, ethane-1, 2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl.

Also preferred are the benzimidazoles of formula (I) wherein

R ⁴ and R ⁴ independently of one another are CF ₃ , C ₂ F ₅ , C _1-6 . ₄ -alkyl, C _{2nd 4} -alkenyl, C _{2nd 4-} alkynyl, C ₃ . ₆ -cycloalkyl, (C ₃ -alkyl-C _{3. 6} cycloalkyl), phenyl or 5-6-membered heteroaryl with 1-2 N, S or O, wherein the phenyl and heteroaryl groups can be substituted by one or two substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, a CH ₃ group, a C ₂ H ₅ group, an OCH ₃ group, an OC ₂ H ₅ group, a CF ₃ group or a C ₂ F ₅ group; The 5-membered cycloalkyl ring may be a nitrogen or oxygen atom in one ring member and in the 6-membered cycloalkyl ring one or two ring members may be nitrogen and / or oxygen atom (s), wherein the ring nitrogen atoms may be optionally substituted cj. _3- alkyl or C _1-3 -alkanoyl.

Also preferred are the benzimidazoles of formula (I) wherein

R ⁵ and R ⁵ independently of one another are a C _1-6 -alkyl group, wherein any carbon atom may be replaced by an oxygen atom, an NH group, an NC group]. _3- alkyl or N-C _1-3 -alkanoyl,

_C3 _7 _{cycloalkyl-Co-3} -alkyl, wherein the five-membered cycloalkyl ring may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members N and / or O, wherein the nitrogen in the ring may be optionally substituted with a C _1-3 -alkyl group or a C _1-3 -alkanoyl group, wherein said C _1-6 -alkyl moiety may be substituted with one of said cycloalkyls or 5-

A 6-membered heteroaromatic having 1-2 heteroatoms selected from nitrogen, sulfur or oxygen, all of said alkyl and cycloalkyl groups being substituted by up to two substituents selected from the group consisting of CF ₃ , OH, or OC]. _3- alkyl, and said heteroaryl may be substituted by one or two substituents selected from the group consisting of fluorine, chlorine, CF ₃ , CH ₃ , C ₂ H ₅ , OCH ₃ , OC ₂ H ₅ , or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7 membered heterocycle which may contain an additional oxygen, nitrogen or sulfur atom and may be substituted with a C 1-4 -alkyl group, C _1-4 -alkoxy-C ₀ . _2- alkyl, C _1-4 -alkoxycarbonyl, aminocarbonyl or phenyl.

Also preferred are the benzimidazoles of formula (I) wherein

A is C-io-alkanediyl, C ₂ .i ₀ -alkéndiylová group, a C ₂ .i ₀ -alkíndiylová group, _{(CO-p-alkanediyl-C3} .7 cycloalkyl-alkanediyl-Co_5 alkanediyl), wherein in a 5-membered cycloalkyl ring, one member of the ring may be nitrogen or oxygen, and in a 6-membered or 7-membered cycloalkyl ring, one or two ring members may be nitrogen and / or oxygen, the nitrogen atoms in the ring optionally substituted by C _1-3 alkyl or C 1-4 -alkanoyl, wherein in said aliphatic chains one or two carbon atoms may be replaced by an oxygen atom, an NH group, an N-C _1-3 -alkyl group or an N-C 1 -alkanoyl group.

Also preferred are the benzimidazoles of formula (I) wherein

B is COOH, COOR ⁵ , CONH ₂ , CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ or tetrazolyl, each of which is bound to a carbon atom in Group A.

Particularly preferred are compounds in which B is COOR ⁵ , CONH ₂ , CONHR ⁵ or CONR ⁵ R ⁵ .

Also preferred are the benzimidazoles of formula (I) wherein

X is a bond or a methylene group.

Also preferred are the benzimidazoles of formula (I) wherein

Y is an oxygen atom.

Preferably especially R ¹ and R ² independently of each other represent a phenyl or 5-6-membered heteroaryl group with

1-2 heteroatoms such as N, O or S, which may be substituted by F, Cl, Br, CN, C _M -alkyl, C _M -alkoxy, metylédioxyskupinou, C |. ₄ alkylthio, a group NO _2, CF _3, NH _2, NH (C |. ₃ alkyl) or N _{(C1. 3} alkyl) _2.

Particularly preferred values for R ³ are hydrogen, fluorine, chlorine, OH, C 1-4 -alkoxy, C 1. _4- alkyl, NO ₂ , NH ₂ , NH-C 1. ₄ -alkanoyl, _{NH-SO2-benzyl,} or NH-SO ₂ -phenyl, where the phenyl radical may be substituted by F, Cl, Br, C ^ -alkyl, C _{first 4-} alkoxy, CF ₃ or acetylamino.

Particularly preferred are the following benzimidazoles: [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -acetic acid isopropyl ester, 3 - [(1,2-diphenyl-1H-benzimidazol-6-yl) methyl ester ) oxy] -propanoic acid, 2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -propanoic acid methyl ester, 4 - [(1,2-diphenyl-1H-benzimidazole-6-) isopropyl ester yl) -oxy] butanoic acid, 5 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid isopropyl ester, 6 - [(1,2-diphenyl-1H-benzimidazole- 6-yl) oxy] hexanoic acid, 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester, 6 - [(1,2-diphenyl-1H-benzimidazole-6- yl) oxy] hexanamide, N-methoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N - (phenylmethoxy) -6 - [(1,2-diphenyl-1)] H-benzimidazol-6-yl) oxy] hexanamide, N-hydroxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, 7 - [(1,2-diphenyl- 6 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-y] isopropyl ester, 1H-benzimidazol-6-yl) oxy] heptanoic acid 1] oxyjhexanoic acid, 6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[2-phenyl-1- [ 3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (3-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (3-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[1- (3-cyanophenyl) -2-phenyl-1H] benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (4-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[isopropyl ester] 1- (4-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] methyl ester 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl 6 - [[1- (4-chlorophenyl) -2-] -, isopropyl ester phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (4-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] isopropyl ester xanoic acid, 6 - [[1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (3-methylphenyl) -2-phenyl- 1H - Benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- 6 - [[1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester Oxy] hexanoic acid, 6 - [[1- (3,5-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (3,5-Dimethylphenyl) isopropyl ester 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (3-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methyl ester 6 - [[1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (3,4-dimethoxyphenyl) -2-phenyl-1H-methyl] methyl ester -benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- [3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexane methyl ester 6 - [[1- [3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2-phenyl-1- (3-methyl) -ethyl] ester 4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- [4- (W) -methyl] hexanoic acid, isopropyl ester , 77-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[l- [4 - (/ V, and ^{L-dimethylamino)} phenyl] -2-phenyl 6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 6 - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, isopropyl ester - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol] 6-yl] oxy] hexanoic acid 6 - [[2- (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[2- (4- chloro-phenyl) -l-phenyl-lH-benzimidazole 6-yl] oxy] hexanoic acid, 6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[2- (4-methylphenyl) phenyl isopropyl ester] 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1-phenyl-2- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methyl ester 6 - [(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid, 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazole-6-) isopropyl ester yl) oxy] hexanoic acid, 6 - [[5 - [[(4-bromophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[methyl ester] 5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino isopropyl ester -1,2-Diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1,2-Diphenyl-5 - [[(3-methylphenyl) sulfonyl] amino] -1H-benzimidazole isopropyl ester 6-yl] oxy] hexanoic acid, 6 - [[1,2-diphenyl-5 - [[(4-methylphenyl) sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hex isopropyl ester 6 - [[1,2-diphenyl-5 - [[(4-methoxyphenyl) sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[1,2-isopropyl ester] 6 - [[5 - [[[4- (acetylamino) phenyl] diphenyl-5 - [[[(4-trifluoromethyl) phenyl] sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[bis (3-chlorophenyl) sulfonyl] -amino] -amino] isopropyl ester - 6 - [[1,2-Diphenyl-5 - [(propylsulfonyl) amino] -1H-benzimidazol-6-yl] oxy, 1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid Hexanoic acid, 6 - [[5 - [(benzylsulfonyl) amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 2- [2 - [(1,2-Diphenyl) methyl ester 3- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] ethoxy] propanoic acid methyl ester, 6-ethyl-6-yl) ethoxy] acetic acid, ethyl ester of 6- 6 - [[4-acetyl-1- (4-methylphenyl) -2-phenyl-1H-methyl] - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester, 6 - [[2-phenyl] -benzimidazol-6-yl] oxy] hexanoate 6 - [[2-phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazol-6-yl] -1- [4- (thiomethyl) phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester 6 - [[2-phenyl-1- (3-thienyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid, methyl 6 - [[2-phenyl-1 - ( 3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -butanoic acid methyl ester, N - (phenylmethoxy) - 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanamide, N, N-dimethyl-6 - [(1,2-diphenyl-1H) N-isopropyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide,

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-pyrrolidin-1-yl-hexan-1-one, 5 - [[5 - [[(4-chlorophenyl) methyl ester] Sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methylphenyl) methyl ester 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H- Benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[4- (acetyloxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[4-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[4-hydroxy-1- (4-methylphenyl) - 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[7-methyl-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] methyl ester hexanoic acid, 6 - [[2-phenyl-1- (3-pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester, methyl 6 - [[2-phenyl-1- (3-pyridyl) - 1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl ester 6 - [[2-phenyl-1- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2- (4-fluorophenyl) -1-phenyl-1H-benzimidazole-, methyl ester] - 6-yl] oxy] hexanoic acid, 6 - [[2- (4-methoxyphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[2- (4-bromophenyl) methyl ester] 1-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2- [4- (trifluoromethyl) phenyl] -1-phenyl-1H-benzimidazol-6-yl] oxy] methyl ester hexanoic acid, 6 - [[1-phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1-phenyl-2- (benzothien-2-) yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy isopropyl ester Hexanoic acid 6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5-methoxy-1- (4-isopropyl ester)] 6-methyl- [5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] methyl] -2-phenyl-1 H -benzoimidazol-6-yl] oxyxane oxy] hexanoic acid, 6 - [[5 6-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- ( 3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -2- (4-fluorophenyl) methyl ester 1- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-methyl ester - (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 4 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl methyl ester -1H-benzimidazol-6-yl] oxy] butanoic acid, 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazole-6-methyl ester 5-aryloxy-pentanoic acid 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester [5 - [[(4- (trifluoromethyl) phenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5- [[(4-chlorophenyl) sulfonyl 1] methylamino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (indan-5-yl) -2-phenyl-1H] -methyl ester 6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl 6 - [[1- (benzimidazol-6-yl) oxy] hexanoic acid; 6 - [[2- (4-Nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] - (3-fluorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1-phenyl-2- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, N - (cyclopropylmethoxy) -6 - [(1,2-diphenyl- 1H-benzimidazol-6-yl) oxy] hexanamide, N-isobutoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N- (cyclopropylmethoxy) -6- [2- phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide, N-isobutoxy-6- [2-phenyl-1- (3,4,5-trimethoxyphenyl) -1 N - (2-methoxyethyl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N- (3-methoxypropyl) - N -benzimidazol-6-yl) oxy] hexanamide 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N-isobutyl-6 - [(1,2-diphenyl-1H) benzimidazole-6-yl) oxy] hexanamide,

6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-morpholin-1-yl-hexan-1-one, N, N-di- (2-methoxyethyl) -6- [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N-isopentyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide; - (pyrid-2-yl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N- (pyrid-3-yl) -6 - [(1,2- diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N-isopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N, N-dimethyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N, N-diethyl-6 - [[1- ( 3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N-isobutyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazole-6] N-cyclopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N-cyclobutyl-6 - [[1-yl] oxy] hexanamide; - (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N-tert-butyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1] (R) -6 - [[1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimide] -benzimidazol-6-yl] oxy] hexanamide zol-6-yl] oxy] -1- (2-methoxymethyl) pyrrolidin-1-ylhexan-1-one, N- (3-imidazol-1-ylpropyl) -6 - [[1- (3,4-dimethylphenyl) ) -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanamide,

N- (2-pyrid-2-yl-ethyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N- (3 Methoxypropyl) -6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] heptanamide, 6 - [[1- (4-Methylphenyl) -2-] methyl ester (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (4-methylphenyl) -2- (4-pyridyl) -1H-benzimidazol-6-yl] methyl ester oxy] hexanoic acid, 6 - [[1- (4-methylphenyl) -2- (2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1 - ( 4-methylphenyl) -2- (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2- (3-indolyl) -1- (4-methylphenyl) -] -, methyl ester 1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (4-methylphenyl) -2- (2-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (4-methylphenyl) -2- (3-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (4-methylphenyl) - 2- (5-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[[[1- (4-methylphenyl) -2- (3-methyl-2-thienyl) methyl] ester -lH-benzimidazole imidazol-6-yl] oxy] hexanoic acid.

The benzimidazole derivatives of the invention inhibit the activation of microglia and can therefore be used to prepare a medicament for the treatment or prophylaxis of diseases that are associated with microglia. By microglia is meant brain macrophages.

This effect is surprising since the use of benzimidazole derivatives for the treatment of thromboses and arteriosclerosis only (EP 0531883, WO 95/07263, EP 0104727, WO 97/12613), cystitis (WO 97/33873) and diseases associated with β- amyloid peptide (US 5,552,426) and enhanced Cakanal activation (EP 520200); the effect on microglia has not been known to date.

The invention also relates to the use of the benzimidazole of the general formula (II)

where

R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group consisting of N, S or O, wherein said aryl or heteroaryl the group may be independently substituted with up to three of the following substituents:

fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH 2, C ( NR ⁴ ) NHR ⁴ , C (NR ⁴ ) NR ⁴ R ⁴ , XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ^4, group XSR ^4, group XSOR ^4, group XSO2R ^4, the group SO 2 NH _2, SO ₂ NHR ^4, a group SO 2 NR ⁴ R ^4, NO 2, XNH _2, groups XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ⁴ , XN (SO ² R ⁴ ) (SO ² R ⁴ ), XNR ⁴ SO ² R ⁴ , XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxo-pyrrol-1-yl, 2,5- dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-diox oisoindol-1-yl or R ⁴ , wherein the two substituents on R ¹ , when in the ortho position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3 -diyl or butane-1,4-diyl,

R ² is a mono- or bicyclic C _{6.] 0} -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group consisting of N, S or O, where the specified aryl or the heteroaryl group may be independently substituted with up to three of the following substituents:

fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH 2, C (NR) ⁴ ) NHR ⁴ , C (NR ⁴ ) NR ⁴ R ⁴ , XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC ( NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ^4, a group XSR ^4, group XSOR ^4, group XSO2R ^4, the group SO 2 NH _2, SO ₂ NHR ^4, a group SO 2 NR ⁴ R ^4, NO 2, XNH _2, groups XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ⁴ , XN (SO 2 R ⁴⁾ (SO 2 R ⁴⁾ SO 2 R ⁴ XNR group ^4, group ⁴ XNHCOR, XNHCOOR group ^4, group XNHCONHR ^4, tetrahydro-2,5-dioxo-pyrrol-l-yl, 2,5-dihydro- -2,5-dioxopyrrol-1-yl test, 2,7-dihydro-2,7- dioxoisoindol-1-yl or R ⁴ , wherein the two substituents on R ² , when in the ortho position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3 -diyl or butane-1,4-diyl,

R ³ is one or two substituents, which independently of one another may be:

hydrogen, fluorine, chlorine, bromine, iodine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR) ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH2, SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO2, XNH2, XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ XNR ⁴ SO ₂ R ⁴ ', XN (SO ₂ R ⁴ ) (SO ₂ R ⁴ '), XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxopyrol-1-yl, 2,5-dihydro -2,5-dioxo-pyrrol-1-yl,

A 2,7-dihydro-2,7-dioxoisoindol-1-yl group or an R ⁴ group, wherein the two R ³ substituents, when in ortho position to each other, may be joined together to form a methanediylbisoxy group, ethane-1, 2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl,

R ⁴ and R ⁴ independently of one another are C _1-4 -fluoroalkyl, C _1-4 . ₆ -alkyl, C _{2nd 6} -alkenyl, C _{2nd 6} -alkynyl, C _{3-_7} cycloalkyl, (C _{3 -alkyl-C3} _7 cycloalkyl), C ₃ -alkyl-C _6. | _O- aryl, C _1-3 -alkyl-substituted 5-10-membered heteroaryl having 1-4 nitrogen, sulfur or oxygen atoms, C ₆ . ₁₀ -aryl or 5-10-membered heteroaryl with 1-4 N, S or O, wherein the _{C6-_io} the aryl and heteroaryl groups can be substituted by one or two of the group comprising fluorine, chlorine, a bromine atom, a CH ₃ group, a C ₂ H ₅ group, a NO ₂ group, an OCH ₃ group, an OC ₂ H ₅ group, a CF ₃ group or a C ₂ F _{5 group} , or may also carry an fused methanediyl bisoxy group or wherein in the five-membered cycloalkyl ring one member of the ring may be a nitrogen or oxygen atom and in the six-membered or seven-membered cycloalkyl ring one or two of the ring members may be a nitrogen and / or oxygen atom, the nitrogen atoms in the ring optionally being C | _ ₃ -alkyl or a C ₃ -alkanoyl,

R ⁵ and R ⁵ independently of one another are hydrogen, C 1-6 alkyl; ₆ -alkyl, C _{2nd 6-} alkenyl or C ₂ . _6- alkynyl, wherein any carbon atom can be replaced by oxygen, sulfur, SO, SO ₂ , NH, N-C 1. _3- alkyl or N-C 1 -alkanoyl,

_C3 .7 cycloalkyl-C _{0th A 3-} alkyl group wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen and one of the six-membered seven-membered cycloalkyl ring may be nitrogen and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted with C _1-3 -alkyl or C _1-3 -alkanoyl,

_Io _C6-aryl or a 5-10-membered heteroaryl with 1-4 heteroatoms from the group N, S and O, wherein the said alkyl, alkenyl and alkynyl may be substituted with one of said cycloalkyl, aryl or heteroaryl groups, all of the foregoing alkyl and cycloalkyl groups being substituted by up to two substituents selected from the group consisting of CF ₃ , C ₂ F ₅ , OH, O-C _1-3 -alkyl, NH ₂ , NH C]. _3-alkyl, NH-C ₃ -alkanoyl, N (C _{(. 3} alkyl) _2, N (C ₃ alkyl) (C _b3 alkanoyl), COOH, CONH _2, COO-Cu -alkyl, and all the aforementioned aryl and heteroaryl groups may be substituted by one or two substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, a CH ₃ group, a C ₂ H ₅ group, a NO ₂ group, OCH ₃ groups, OC ₂ H ₅ groups, CF ₃ groups and C ₂ F ₅ groups, or may also carry a fused methanediylbisoxy or ethane-1,2-diyl-bisoxy group, or R ⁵ and R ⁵ together with the nitrogen atom form a 5- 7-membered heterocycle containing a further oxygen, nitrogen or sulfur and is optionally substituted C _M -alkyl, _C.-4 alkoxy Co_ ₂ -alkyl, C. _{4-alkoxy-carbonyl,} aminocarbonyl or phenyl group,

A is C | ₀ _i -alkanediyl, C _{2nd 10} -alkéndiylová group, a C _{2nd 10} -alkíndiylová group, a group (C ₀ -5 alkanediyl-C ₃ .7-cycloalkanediyl-Co-5 alkanediyl) group (Co.5-alkándiylarylén _the C-.5-alkanediyl) group, (C ₀ .5 -alkanediyl-heteroarylene-C0-8-alkanediyl) wherein the aryl and heteroaryl groups may be substituted by one or two substituents from the group fluorine atom, chlorine atom, bromine atom, methyl group, ethyl group, NO ₂ group, OCH ₃ group, OC ₂ H ₅ , CF ₃ , C ₂ F ₅ , wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen, and the six-membered or seven-membered cycloalkyl ring may be nitrogen and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted with C 1. ₃ 11

-alkyl or a C ₃ -alkanoyl, wherein the aliphatic chains mentioned above, one or two carbon atoms may be exchanged for O, NH, NR ^4, NCOR ⁴ group, or a group NSO2R ^4, and the alkyl, or cycloalkyl groups may be substituted by up to two substituents selected from the group consisting of fluorine atom, OH group, OR ⁴ group, OCOR ⁴ group, = O group, NH 2 group, NR ⁴ R ⁴ group, NHCOR ⁴ group, NHCOOR ⁴ group, NHCONHR ⁴ , NHSO ₂ R ⁴ , SH and SR ⁴ groups,

B is hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COR ⁵ , C (NOH) R ⁵ , C (NOR ⁵ ) R ⁵ , C (NO (COR ⁵ )) R ⁵ , COOH, COOR ⁵ , CONH2, CONHNH2, CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ , SO 3 H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO2NR ⁵ R ⁵ , PO 3 OH, PO (OH) (OR ⁵ ), PO (OR ⁵ ) (OR ⁵ '), PO (OH) (NHR ⁵ ), PO (NHR ⁵ ) (NHR ⁵ ') or tetrazolyl, each of which is linked to a carbon atom of A, or a whole group of YAB is N (SO ₂ R ⁴⁾ (SO 2 R ⁴⁾ or the group NHSO 2 R ^4,

X is a bond, CH ₂ , (CH ₂ ) ₂ , CH (CH ₃ ), (CH ₂ ) ₃ , CH (CH ₂ CH ₃ ), CH (CH ₃ ) CH ₂ , CH ₂ CH (CH _3),

Y is a bond, oxygen, sulfur, SO, SO ₂ , NH, NR ⁴ , NCOR ^4, or NSO ₂ R ⁴ , for the preparation of a medicament for the treatment or prophylaxis of diseases associated with the activation of microglia.

In addition to the novel compounds of formula (I), the formula (II) also comprises known compounds (EP 0 531 883, DE 4330959). The compounds according to the invention of formula (II) suppress the activation of microglia. This effect is new, even for the compounds already known.

Preferred is the use of compounds of formula (II) wherein

R is a monocyclic or bicyclic aryl group or a monocyclic or bicyclic 5-10-membered heteroaryl group with 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, said aryl or heteroaryl group being independently substituted with up to three with the following substituents:

fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH 2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO 2, XNHR ⁴ , XNR ⁴ R ^4, or R ⁴ , wherein the two substituents on R ¹ are ortho to each other position, they can be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl.

Also preferred is the use of compounds of formula (II) wherein

R ² is a mono- or bicyclic aryl or mono- or bicyclic 5-10 cyclic-membered heteroaryl having 1-2 heteroatoms selected from the group consisting of N, S or O, wherein said aryl or heteroaryl group may be independently substituted with up to three of the following substituents:

fluorine atom, chlorine atom, bromine atom, XOH group, XOR ⁴ group, XOCOR ⁴ group, XOCONHR ⁴ group, XOCOOR ⁴ group, XCOR ⁴ group, XC (NOH) R ⁴ group, XC (NOR ⁴ ) R ⁴ group, XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR, XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ^4, a group XSO2R ^4, SO ₂ NH _2, SO ₂ NHR ^4, a group SO 2 NR ⁴ R ^4, NO 2, XNH _2, groups XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ^4, XN (SO 2 R ⁴ ) (sO 2 R ⁴⁾ group, XNR ⁴ sO 2 R ^4, a group XNHCOR ^4, group XNHCOOR ^4, group XNHCONHR ^4, or a group R ^4, where two substituents on R ^2, where they are in the ortho position, can be linked to the together form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-yl.

Also preferred is the use of compounds of formula (II) wherein

R ³ is one or two substituents independently of one another:

hydrogen, fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO2NH ₂ , SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO2, XNH2, XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ , XNR ⁴ SO ₂ R ⁴ ,

XN (SO ₂ R ⁴ ) (SO ₂ R ⁴ '), XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ^4, or R ⁴ , wherein the two R ³ substituents, when in ortho position, may be joined together together that form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl.

Also preferred is the use of compounds of formula (II) wherein

R ⁴ and R ^4, independently of one another are CF _3, C ₂ F _5, C _M alkyl, C ^ -alkenyl, C _{2nd 4-} alkynyl, C ₃ . ₆ -cycloalkyl, (C ₃ -alkyl-C _{3. 6} cycloalkyl), C. _{A 3-} alkylaryl group, C 1. _{A 3-} alkylheteroaryl group, a monocyclic aryl group or a 5-6-membered heteroaryl group having 1-2 nitrogen, sulfur or oxygen atoms, wherein the aryl and heteroaryl groups may be substituted by one or two substituents from the group containing a fluorine atom, a chlorine atom, a bromine atom, a CH ₃ group, a C ₂ H ₅ group, a NO ₂ group, an OCH ₃ group, an OC ₂ H ₅ group, a CF ₃ group or a C ₂ F _{5 group} or may also carry fused methanediylbisoxy or ethane-1,2-diyl bisoxy, wherein in the five-membered cycloalkyl ring one member of the ring may be a nitrogen or oxygen atom and in the six-membered cycloalkyl ring one or two member of the ring may be a nitrogen atom and / or an oxygen atom, the nitrogen atoms in the ring optionally being C 1 substituted. _3- alkyl or C _1-3 -alkanoyl.

Also preferred is the use of compounds of formula (II) wherein

R ⁵ and R ⁵ independently of one another are C 1-6. _6- alkyl, wherein any carbon atom may be replaced by oxygen, NH, N-C _1-3 -alkyl or N-C _1-3 -alkanoyl, C ₃ . ₇ -cycloalkyl-Co. _3-alkyl, wherein the five-membered cycloalkyl ring may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members N and / or O, wherein ring nitrogen atoms can be optionally substituted with C _{1st 3} -alkyl or a C ₃ -alkanoyl, wherein said C _d6 -alkyl moiety may be substituted by one of the mentioned cycloalkyl groups or else one of the 5-6-membered heteroaromatic with 1-2 heteroatoms selected from the group consisting of a nitrogen atom , sulfur or oxygen, all of the foregoing alkyl and cycloalkyl groups being substituted with up to two substituents selected from the group consisting of CF ₃ , OH, O-C _1-3 -alkyl, and heteroaryl groups mentioned above. be substituted by one or two substituents selected from the group consisting of fluorine atom, chlorine atom, CF ₃ group, CH ₃ group, C ₂ H ₅ group, OCH ₃ group and OC ₂ H _{5 group} , or R ⁵ and R ⁵ together with the nitrogen atom forms a 5-7 membered heterocycle which may contain an additional oxygen, nitrogen or sulfur atom and may be substituted Ci. _4- alkyl, C 1-6 alkyl; _4- Alkoxy-C ₀ . _2- alkyl, C _1-4 -alkoxycarbonyl, aminocarbonyl or phenyl.

Also preferred is the use of compounds of formula (II) wherein

A is a Ci.io-alkanediyl, C ₂ _i ₀ -alkéndiylová group, a C ₂ _i ₀ -alkíndiylová group, a group (C0.5-alkanediyl-C ₃ _7-cycloalkanediyl-Co-5 alkanediyl) group or a (Co s-alkanediyl-heteroarylene-C0- s-alkanediyl), wherein the optionally present heteroaryl group may be substituted by one or two substituents from the group fluorine, chlorine, bromine, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF _3, and C ₂ F ₅ , wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen and the six-membered or seven-membered cycloalkyl ring may be one or two ring members and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted by a C _1-3 -alkyl or a C _3-3 -alkanoyl group, wherein in the aliphatic chain one or two carbon atoms may be replaced by an oxygen atom, NH, N-C _1-3 -alkyl, NC]. _3- alkanoyl or NSO ₂ C 1. ₃ alkyl, and the alkyl or cycloalkyl moieties may be substituted with up to two fluorine atoms, or one of the substituents of the group consisting of OH, OC _B3 -alkyl, O-C ₃ -alkanoyl, = 0 atom, NH ₂ , NH-C 1 groups. _3- alkyl, N (C _1-3 -alkyl) ₂ , NHC ₁ groups. ₃ -alkanoyl, N (C _1-3 -alkyl) (C _1-3 -alkanoyl), NHCOOC _1-3 -alkyl, NHCONHCl groups. _3- alkyl, NHSO ₂ Ci. _3- alkyl, SH groups and SCu-alkyl groups.

Also preferred is the use of compounds of formula (II) wherein

B is hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COOH, COOR ⁵ , CONH ₂ , CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ or tetrazolyl each of which is bound to a carbon atom of group A.

Also preferred is the use of compounds of formula (II) wherein

X is a bond or a CH ₂ group.

Also preferred is the use of compounds of formula (II) wherein

Y is a bond, an oxygen atom, a sulfur atom, an NH group, an NR ⁴ group, an NCOR ⁴ group, or an NSO ₂ R ^{4 group} .

Example 307 illustrates how inhibition of microglia activation can be measured. Activation of microglia can be achieved by various stimulators, such as β-peptide (β-amyloid; Araujo, DM and Cotman, CM, Brain Res. 569, 141-145 (1992)), prion protein, cytokines or cell fragments (Combs, CK et al. J. Neurosci. 19, 928-939 (1999); Wood, PL Neuroinflammation: Mechanisms and Management, 1998, Humana Press). For example, Example 49, isopropyl 6 [[l- (4-methylphenyl) -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanoic acid, the inhibition _IC50 = 0.75 μΜ.

Stimulation with β-peptides corresponds to the pathophysiological situation in Alzheimer's disease. In this assay, during the stimulation with β-peptide, the compounds of the invention inhibited microglia activation. Suppression of microglia activation by the compounds of the invention results in a strong reduction in the production and secretion of cytokines such as IIIβ and TNFα (as measured by ELISA and mRNA expression analysis) and reduced secretion of the reactive oxygen / nitrogen intermediate. At the same time, several inflammatory factors are also suppressed.

The in vivo efficacy of the compounds of the invention has been demonstrated in the MCAO rat model. This model simulates a stroke condition. The compounds of the invention reduce microglia activation, which occurs in acute damage to the animal brain.

The invention also relates to the use of the compounds according to the invention of formula (I) and formula (II) for the preparation of a medicament for the treatment or prophylaxis of diseases associated with the activation of microglia. Examples of such diseases are dementia due to AIDS, amyotrophic lateral sclerosis, Creuzfeld-Jacob disease, Down's syndrome, dementia due to diffuse inclusion of Lewy bodies in the cerebral cortex, Huntington's disease, leukoencephalopathy, multiple sclerosis, Pickinson's disease, Pickinson's disease, Parkinson's disease, Parkinson's disease temporal lobe and tumors.

The invention further relates to pharmaceutical compositions comprising one or more compounds of formula (I) according to the invention and one or more carriers. Pharmaceutical compositions respectively. the formulations of the invention are prepared in a conventional manner using conventional solid or liquid carriers or diluents and conventional pharmaceutical and technical ingredients, according to the desired application type, in suitable dosages. Preferred are preparations which can be administered orally, enterally or parenterally. Such dosage forms are, for example, tablets, coated tablets, dragees, pills, capsules, powder or depot forms such as suppositories. Corresponding tablets may be prepared, for example, by mixing the active ingredient with known ingredients, for example, inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinylpyrrolidone, raising agents such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as is carboxypolymethylene, carboxymethylcellulose, cellulose acetate phthalate or polyvinyl acetate. The tablets may also consist of several layers.

Similarly, dragees can be prepared. Cores prepared analogously to tablets are coated with conventional coatings such as polyvinylpyrrolidone or shellac, acacia, talc, titanium oxide or sugar. The inside of the dragee can also consist of several layers, the additives already mentioned for tablets being used. For example, capsules containing the active ingredients can be prepared by mixing the active ingredient with milk sugar or sorbitol and filling the gelatin capsules with the mixture.

The compounds of the invention may also be used in suitable solutions, such as saline, for infusion or injection.

Particularly suitable for parenteral administration are oily solutions, such as those in sesame oil, castor oil and cottonseed oil. Solubilizers such as benzyl benzoate or benzyl alcohol may be added to increase solubility.

The compounds of the invention may also be incorporated into the transdermal system and thus administered transdermally.

The dosage of the compounds of formula (I) and formula (II) according to the invention will be determined by the attending physician and will depend, inter alia, on the compound to be administered, the route of administration, the condition being treated and its severity. The daily dose of the compound does not exceed 1000 mg, preferably not more than 100 mg, and can be administered in a single dose or in 2 or more divided doses per day.

The compounds of formula (I) may exist as tautomers, stereoisomers or geometric isomers. The invention also relates to all possible isomers, such as E- and Z-isomers, S- and R-enantiomers, diastereoisomers, racemates and mixtures thereof, including tautomeric compounds.

Mixtures of isomers may be separated into enantiomers or E / Z-isomers by conventional methods such as crystallization, chromatography or salt formation.

The compounds of the invention may be prepared analogously to known procedures, such as described in EP 531 883. If the preparation of the starting compounds is not described, these starting compounds are known and commercially available or prepared analogously to the procedures described herein. The following describes the preparation of some precursors, intermediates and products.

DETAILED DESCRIPTION OF THE INVENTION

For example, the following methods are used to prepare the compounds of the invention:

General Regulation 1

Reduction of nitro groups, hydrogenation of olefinic double bonds and hydrogenolytic cleavage of benzyl ethers

The reduced compound is dissolved in ethyl acetate, tetrahydrofuran, methanol or ethanol, or a mixture of solvents and hydrogenated at atmospheric pressure to 2-5% (relative to nitro compound) of palladium on carbon (10%). After completion of the hydrogen uptake, the catalyst is filtered off with suction, washed with ethyl acetate, methanol or ethanol and the filtrate is concentrated in vacuo. The crude product is generally used without further purification.

General Regulation 2 Reduction of nitro groups

Dissolve 9.2 g of ferrous sulphate in 30 ml of water and add 9 ml of ammonia solution. To this was added dropwise a solution of 3.6 mmol of the nitro compound in 100 ml of ethanol, and the suspension was stirred vigorously at 70 ° C for 1 hour. The mixture is allowed to settle, the solid is filtered off, the filtrate is concentrated to near dryness, water is added and extracted three times with ethyl acetate. The combined extracts were dried over sodium sulfate and evaporated in vacuo. The obtained amino compound is further processed in the crude state.

General Regulation 3 Cyclization to benzimidazoles by reaction with orthoesters of a mmol of the 1,2-diaminobenzene derivative is dissolved in 25 ml of ethanol. To this solution was added dropwise 47 ml of 0.8M ethereal hydrogen chloride solution, the mixture was stirred for 30 minutes and then evaporated to dryness in vacuo. The evaporation residue is dissolved in 230 ml of methanol and 6 ml of trimethyl orthobenzoate or an equivalent amount of another orthoester is added. The mixture was heated at reflux for 2-8 hours, poured into saturated sodium bicarbonate solution, cooled, extracted three times with ethyl acetate, the combined extracts were dried over sodium sulfate and the solvent was evaporated in vacuo. The residue was purified by crystallization or silica gel column chromatography.

General Regulation

Cyclization to benzimidazoles with iminoester hydrochlorides

1.2 mmol of the 1,2-diaminobenzene derivative are dissolved in 5 ml of tetrahydrofuran, 1.5 mmol of benzimidate hydrochloride are added and the mixture is stirred for 15 hours. Saturated sodium bicarbonate solution was added, the mixture was diluted with water and extracted three times with ethyl acetate. The combined organic phases are washed three times with 1 N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulfate, filtered through a fritted silica gel and the filtrate is evaporated to dryness. The product is crystallized from diisopropyl ether.

General Regulation

Cyclization to benzimidazoles via carboxylic acid anilides

The 4.7 mmol of the 1,2-diaminobenzene derivative is dissolved in 20 ml of dichloromethane, 14 mmol of triethylamine are added, 6 mmol of carboxylic acid chloride are added slowly, and the mixture is then stirred for 15 hours. Saturated sodium bicarbonate solution was added to the reaction mixture, diluted with water and extracted twice with dichloromethane. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The remaining crude acid anilide was dissolved in a 9: 1 mixture of methanol and concentrated hydrochloric acid and refluxed for 1 hour. After cooling, the reaction mixture was slowly transferred to a saturated sodium bicarbonate solution, diluted with water and extracted three times with dichloromethane. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated in vacuo. The evaporation residue is purified by crystallization or by silica gel column chromatography as necessary.

General Regulation

Cleavage of ethers with hydrobromic acid

A mixture of 5 g of aryl methyl ether and 160 ml of 48% aqueous hydrobromic acid is refluxed for 1-5 hours and, after cooling, the reaction mixture is filtered off. The residue was dissolved in ethyl acetate, extracted three times with saturated sodium bicarbonate solution, and, after drying over sodium sulfate, evaporated in vacuo. The evaporation residue is purified by crystallization or by silica gel column chromatography as necessary.

General regulation 7 Cleavage of ethers with boron tribromide

To a solution of aryl methyl ether (1.86 mmol) in dichloromethane (18 mL) was slowly added boron tribromide (7.4 mL, 1 M in dichloromethane) at -35 ° C. The mixture was allowed to stand for 12-15 hours at -30 ° C, then saturated sodium bicarbonate solution was added, extracted three times with dichloromethane, the combined extracts were dried over sodium sulfate and concentrated in vacuo. The evaporation residue is purified by silica gel column chromatography as necessary.

General Regulation

Alkylation of hydroxybenzimidazole derivatives and phenol derivatives by reaction with halides

To a solution of 1.85 mmol of the hydroxybenzimidazole derivative in 12 mL of N, N-dimethylformamide was added 1.85 mmol of cesium carbonate and 2.24 mmol of alkyl bromide or alkyl iodide. If alkyl bromide is used, 1.85 mmol of sodium iodide are optionally added. The mixture is stirred for 12-96 hours, then poured into water, extracted into ethyl acetate, the organic phase is washed four times with water, dried over sodium sulphate and concentrated in vacuo.

Alternatively to this aqueous treatment, dichloromethane may also be added to the reaction mixture, the precipitated salts may be removed by filtration, and the filtrate concentrated in vacuo.

Irrespective of the processing method, the residue is then purified by crystallization or silica gel column chromatography.

General rule 9 Saponification of alkyl esters of carboxylic acids

To a solution of carboxylic acid alkyl ester (0.77 mmol) in methanol (5 ml) and tetrahydrofuran (5 ml) was added 0.5 N aqueous lithium hydroxide or sodium hydroxide (5 ml). The mixture was stirred for 2-12 hours, then concentrated to dryness in vacuo, neutralized by the addition of aqueous hydrochloric acid, and extracted with ethyl acetate. After drying over sodium sulfate and evaporation of the solvent, the residue is purified by silica gel column chromatography as necessary.

General Regulation 10 Esterification of carboxylic acids

To a solution of 0.2 mmol of carboxylic acid in 1 mL of primary or secondary alcohol was added two drops of concentrated sulfuric acid and the solution was stirred for 12 hours at 60 ° C. Saturated potassium bicarbonate solution was added, the mixture was diluted with water and extracted three times with ethyl acetate. The combined extracts were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The evaporation residue is crystallized from diisopropyl ether.

General rule 11

Reduction of alkyl esters of carboxylic acids with lithium aluminum hydride

To a solution of the carboxylic acid ester (0.15 mmol) in tetrahydrofuran was added 0.09 mmol of lithium aluminum hydride. The reaction mixture was stirred for 1-48 hours, quenched with water and extracted three times with dichloromethane. The combined organic phases are dried over sodium sulphate and concentrated in vacuo. The evaporation residue is purified by crystallization or by silica gel column chromatography as necessary.

General Regulation

Wittig reaction of benzimidazolecarbaldehydes with (ω-carboxyalkyl) -triphenylphosphonium bromides and esterification with methanol

To 2 mmol of (1-carboxyalkyl) triphenylphosphonium bromide in 2.5 ml of dimethylsulfoxide and 2.5 ml of tetrahydrofuran at 0 ° C was added 4 mmol of potassium tert-butoxide, and the mixture was stirred at> 10 ° C for 30 minutes. A solution of aldehyde (0.67 mmol) in tetrahydrofuran (2 mL) was then added and the mixture was stirred at 20 ° C for 3 h. Saturated ammonium chloride solution was added, the mixture was diluted with water and extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated in vacuo. The residue is dissolved in 15 ml of methanol, two drops of concentrated sulfuric acid are added and allowed to stand for 48-72 hours. After concentration in vacuo, the residue was purified by silica gel column chromatography.

General Regulation 13

Reaction of aminobenzimidazoles with alkyl- and arylsulfonic acid halides

To a solution of 47 gmol of the aminobenzimidazole derivative in 0.5 ml of dichloromethane was added 51 µl of triethylamine and 51 gmol of alkyl or arylsulfonic acid halide and the reaction mixture was stirred for 2-15 hours. Saturated sodium bicarbonate solution is added, extracted three times with dichloromethane, the combined organic phases are dried over sodium sulfate and concentrated in vacuo. The evaporation residue is purified by crystallization or silica gel column chromatography.

General Regulation

Copper-mediated O- or N-arylation of benzimidazoles

5 mmol of the A-unsubstituted benzimidazole derivative or the A-arylsubstituted hydroxybenzimidazole derivative are dissolved in 20 ml of dichloromethane. Add 10 mmol of arylboronic acid, 5 mmol of anhydrous cupric acetate, 10 mmol of pyridine or triethylamine and about 2.5 g of molecular sieve (4) and stir for 48-72 hours while eliminating moisture. Silica gel is added, the mixture is dried in vacuo and the powder remaining is chromatographed on silica gel. If desired, regioisomeric A-aryl products are separated by HPLC.

General rule 15

Basic catalyzed A-substitution of benzimidazoles

To a solution of 5 mmol of the A-unsubstituted benzimidazole derivative in 20 mL of dimethylacetamide was added 25 mmol of sodium hydride and 20 mmol of electron deficient aryl halide or heteroaryl halide, and the mixture was refluxed for 48-72 hours, excluding moisture. Silica gel was then added, evaporated to dryness in vacuo and the remaining powder chromatographed on silica gel. If desired, regioisomeric A-aryl products are separated by HPLC.

General regulation 16 Cyclization to benzimidazoles by reaction with aldehydes

To a solution of 1 mmol of the 1,2-diaminobenzene derivative in 3 ml of nitrobenzene is added 1 mmol of aryl or heteroaryl aldehyde. The mixture was heated at 150 ° C for 2-6 hours and then allowed to cool. The residue was purified by silica gel column chromatography without further work-up.

General Regulation

Conversion of carboxylic acids to carboxamides

To a solution of 0.25 mmol of carboxylic acid in 3 ml of N, N-dimethylformamide was added 0.38 mmol of primary or secondary amine, 0.5 mmol of triethylamine and 0.25 mmol of diphenylphosphoryl azide and the mixture was allowed to stir for 2 days. The reaction mixture is quenched by the addition of water, extracted three times with ethyl acetate, the combined organic phases are washed with water, dried over sodium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography.

General Regulation

Conversion of carboxylic acid esters to carboxamides

To a solution of 0.36 mmol of the amine in 3 ml of toluene is added dropwise, while cooling in an ice bath, 0.18 ml.

M solution of trimethylaluminium in toluene. Then a solution of 0.33 mmol of carboxylic acid methyl ester in 3 ml of toluene is added and stirred for 2 to 8 hours at 95 ° C. After cooling, water is added, extracted three times with ethyl acetate, the combined organic layers are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography.

Example 1

[(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] acetic acid isopropyl ester

The compound is prepared by reacting 1,2-diphenyl-6-hydroxy-1H-benzimidazole (Benincori, T .; Sannicolo, F., J. Heterocycl. Chem., 25, 1988, 1029-1033) with isopropyl ester of bromoacetate according to the general formula 8th

T. t. 137-138 ° C.

Example 2 [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] ethan-1-ol

The compound is prepared from [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] acetic acid methyl ester (DE 4330959) according to the general formula 11.

1 H-NMR (d ₆ -DMSO): δ (δριη): 3.72 t (J = 7.5 Hz, 2H); 4.02 t (J = 7.5Hz, 2H); 6.72 d (J = 2Hz, 1 H); 7.10 dd (J = 8.2 Hz, 1H); 7.38-7.68 m (10H); 7.76 d (J = 8Hz, 1 H).

Example 3

- [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] propan-1-ol

0.5 g of 1,2-diphenyl-6-hydroxy-1H-benzimidazole was reacted with 3- (bromopropoxy) -tert-butyl-dimethylsilane according to general formula 8. After chromatography on silica gel, it is dissolved in 2.5 ml of methanol, 0.4 ml of concentrated hydrochloric acid is added and stirred for 2 hours at 20 ° C. The mixture was poured into a saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate, the combined extracts were washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo.

T. t. Mp 191-193 ° C.

Example 4

3 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid

To 100 mg of 3 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] propan-1-ol in 2.5 ml of acetone at -15 ° C is added 0.15 ml of Jones reagent solution ( prepared from 0.27 g of chromium trioxide, 1 ml of water and 0.23 ml of concentrated sulfuric acid). After stirring at -15 ° C for 3.5 hours, the reaction is quenched by addition of isopropanol. The reaction mixture was diluted with water, extracted three times with dichloromethane, the combined organic phases were dried over sodium sulfate and the solvent was evaporated in vacuo. The residue was purified by silica gel chromatography.

1 H-NMR (d 6 -DMSO): δ (ppm): 2.60 t (J = 7.5 Hz, 2H); 4.15 t (J = 7.5Hz, 2H); 6.64 d (J = 2Hz, 1 H); 6.95 dd (J = 8.2Hz, 1H); 7.30-7.61 m (10H); 7.69 d (J = 8Hz, 1 H).

Example 5

3 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -propanoic acid methyl ester mg of 3 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid in 0.5 ml of N, N-dimethylformamide and to the solution 41 mg of cesium carbonate and 10 μΐ of methyl iodide are added. The mixture was stirred for 2 days, then diluted with dichloromethane, filtered off, the filtrate concentrated in vacuo and the residue subjected to silica gel chromatography.

T. t. Mp 120-121 ° C.

Example 6

2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid methyl ester

Prepared by reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 2-bromopropanoic acid methyl ester according to General Regulation 8.

T. t. 132-135 ° C.

Example 7

4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] butanoic acid isopropyl ester

Prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 4-bromobutanoic acid isopropyl ester according to General Regulation 8.

T. t. Mp 89-91 ° C.

Example 8

4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] butan-1-ol

Prepared from methyl 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butanoate according to General Regulation 11.

T. t. Mp 159-160 ° C.

Example 9 [4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] but-1-yl] acetate

To a solution of 50 mg of 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -butan-1-ol in 1 ml of dichloromethane is added 0.34 ml of pyridine and 20 μΐ of acetyl chloride and the mixture is stirred for 15 hours. hours. Saturated sodium bicarbonate solution was added, the mixture was diluted with water and extracted twice with dichloromethane. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue was purified by preparative thin layer chromatography.

T. t. Mp 68-69 ° C.

Example 10 [4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] but-1-yl] pivalate

Prepared in analogy to Example 9 from 50 mg of 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butan-1-ol, 0.34 ml of pyridine and 22 μ a of trimethylacetic acid chloride.

T. t. Mp 104-106 ° C.

Example 11

4 - [(l, 2-diphenyl-lH-benzimidazol-6-yl) oxy] butyl-7V-methylcarbamate

To a solution of 100 mg of 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butan-1-ol in 4 mL of dichloromethane was added 0.1 mL of triethylamine and 20 mg of methyl isocyanate and the mixture was stirred for 15 min. hours. An additional 0.1 ml of triethylamine and 20 mg of methyl isocyanate are then added and the mixture is stirred for 20 hours. It is then concentrated in vacuo and the residue is purified by silica gel chromatography.

T. t. Mp 124-126 ° C.

Example 12

5 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] pentanoic acid isopropyl ester 994

It is prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 5-bromopentanoic acid isopropyl ester according to general formula 8.

T. t. 91-92 ° C.

Example 13

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

H-NMR (CDC1 _3): δ = 1.44 to 1.56 m (2H); 1.64-1.85 m (4H); 2.33 t (J = 7.5Hz, 2H); 3.66 s (3H); 3.93 t (J = 7.5Hz, 2H); 6.70 d (J = 2Hz, 1H); 6.96 dd (J = 8.2 Hz, 1H); 7.22-7.38 m (5H); 7.43-7.58 m (5H); 7.76 d (J = 8Hz, 1 H).

Example 14

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester

Prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.22 d (J = 7.5 Hz, 6H); 1.43-1.56 m (2 H); 1.62-1.87 m (4H); 2.30 t (J = 7.5Hz, 2H); 3.93 t (J = 7.5Hz, 2H); 5.01 sp (J = 7.5Hz, 1H); 6.69 d (J = 2Hz, 1 H); 6.96 dd (J = 8.2 Hz, 1H); 7.25-7.38 m (5H); 7.43-7.55 d (J = 8Hz, 1H).

Example 15

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid

Prepared by reaction of methyl 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoate according to general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.35-1.49 m (2H); 1.50-1.63 m (2H); 1.65-1.77 m (2H); 2.23 t (J = 7.5Hz, 2H); 3.92 t (J = 7.5Hz, 2H); 6.62 d (J = 2Hz, 1 H); 6.95 dd (J = 10.2 Hz, 1H); 7.30-7.62 m (10H); 7.68 d (J = 10Hz, 1 H).

Example 16

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexan-1-ol

Prepared by reaction of methyl 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoate according to General Regulation 11.

1 H-NMR (CDCl 3): δ (ppm): 1.35-1.85 m (8H); 3.67 t (J = 7.5Hz, 2H); 3.98 t (J = 7.5Hz, 2H); 6.70 d (J = 2Hz, 1H); 6.98 dd (J = 8.2 Hz, 1H); 7.24-7.38 m (5H); 7.45-7.58 m (5H); 7.75 d (J = 8Hz, 1H).

Example 17

6 - [(l, 2-diphenyl-lH-benzimidazol-6-yl) oxy] hexanamide

a) 6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanenitrile

It is prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanenitrile according to general formula 8.

T. t. Mp 108-112 ° C.

6 - [(l, 2-diphenyl-lH-benzimidazol-6-yl) oxy] hexanamide

To a solution of 50 mg of 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanenitrile in 1 ml of methanol is added 18 mg of potassium carbonate and 40 μΐ of a 30% hydrogen peroxide solution and stirred for 24 hours. hours. While stirring, ice-cold sodium thiosulphate solution is added and extracted three times with ethyl acetate. After drying over sodium sulfate and evaporation in vacuo, the residue is chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.48-1.60 m (2H); 1.65-1.87 m (4H); 2.25 t (J = 7.5Hz, 2H); 3.94 t (J = 7.5Hz, 2H); 5.30-5.53 br (2H); 6.68 d (J = 2Hz, 1 H); 6.95 dd (J = 8.2 Hz, 1H); 7.23-7.38 m (5H); 7.42-7.58 m (5H); 7.75 d (J = 8Hz, 1H).

Example 18 N-Methoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

100 mg of 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid is dissolved in 2 ml of tetrahydrofuran, 39 mg of carbonyldiimidazole are added, the mixture is stirred at 20 ° C for 30 minutes and then The mixture was heated at reflux for 30 minutes. 21 mg of O-methylhydroxylamine hydrochloride are then added at 20 ° C and stirred for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with 2 N aqueous hydrochloric acid and saturated potassium bicarbonate solution. After drying over sodium sulfate and evaporation in vacuo, the residue is chromatographed on silica gel.

T. t. Mp 144-145 ° C.

Example 19 N- (Phenylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepared by reacting 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid with O-benzylhydroxylamine hydrochloride according to the procedure described in Example 18.

T. t. 144 ° C.

Example 20

N-Hydroxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide mg N- (phenylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) 1-oxy] hexanamide is dissolved in 4 ml of ethanol, 15 mg of palladium on carbon (10%) are added, and the mixture is stirred under a hydrogen atmosphere for 3 hours. After separation of the catalyst, the solvent is removed in vacuo and the residue is crystallized from diethyl ether.

T. t. Mp 83-85 ° C.

Example 21

7 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid methyl ester

Prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 7-bromo-heptanoic acid methyl ester according to general formula 8.

T. t. 77-80 ° C.

Example 22

7 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid

Prepared by reaction of methyl 7 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid according to the general formula 9.

T. t. Mp 142-145 ° C.

Example 23

7 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] heptanoic acid isopropyl ester

Prepared by reacting 7 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid with isopropanol according to the general formula 10.

T. t. 98-100 ° C.

Example 24

6 - [[1- (3-Nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6-hydroxy-1- (3-nitrophenyl) -2-phenyl-1H-benzimidazole (DE 4330959) with 6-bromohexanoic acid isopropyl ester according to general rule 8.

T. t. Mp 111-113 ° C.

Example 25

6 - [[2-Phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) (5-Methoxy-2-nitrophenyl) [(3-trifluoromethyl) phenyl] amine

A mixture of 2 g of 3-fluoro-4-nitroanisole and 16 ml of 3- (trifluoromethyl) aniline is stirred at 140 ° C for 72 hours, then diluted with ethyl acetate, washed ten times with 4 N aqueous hydrochloric acid and once with saturated sodium chloride solution. , dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

1 H-NMR (CDCl 3): δ (ppm): 3.78 s (3H); 6.42 dd (J = 8.2 Hz, 1H); 6.60 d (J = 2Hz, 1 H); 7.45-7.60 m (4H);

8.22 d (J = 8Hz, 1H); 9.78 with br (1H).

b) 6-Methoxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole

It is prepared by hydrogenation of (5-methoxy-2-nitrophenyl) [(3-trifluoromethyl) phenyl] amine according to general formula 1 and subsequent cyclization with triethyl orthobenzoate according to general formula 3.

T. t. Mp 135-137 ° C.

c) 6-Hydroxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole

Prepared from 6-methoxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole according to general formula 6.

1 H-NMR (d 6 -DMSO): δ (ppm): 6.56 d (J = 2 Hz, 1H); 6.82 dd (J = 8.2 Hz, 1H); 7.32-7.50 m (5H); 7.60 d (J = 8Hz, 1H); 7.70-7.95 m (4H); 9.48 with br (1H).

6 - [[2-Phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. 106-108 ° C.

Example 26

6 - [[2-Phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6-hydroxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

T. t. Mp 113-115 ° C.

Example 27

6 - [[2-Phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 156-158 ° C.

Example 28

6 - [[2-phenyl-l- [3- (trifluoromethyl) phenyl] -lH-benzimidazol-6-yl] oxy] hexan-l-ol

Obtained from 6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

T. t. Mp 143-145 ° C.

Example 29

6 - [[1- (3-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (5-Methoxy-2-nitrophenyl) aminobenzonitrile

A mixture of 2 g of 3-fluoro-4-nitroanisole and 15 ml of 3-aminobenzonitrile was stirred at 140 ° C for 65 hours. The reaction mixture was then diluted with ethyl acetate, washed three times with water and once with saturated sodium chloride solution. After drying over sodium sulfate, it is concentrated in vacuo and the residue is chromatographed on silica gel.

T. t. Mp 157-158 ° C.

b) 6-Methoxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole

It is prepared by hydrogenation of 3- (5-methoxy-2-nitrophenyl) aminobenzonitrile according to general formula 1 and subsequent cyclization with triethyl orthobenzoate according to general formula 3. In cyclization, unlike the general formula, tetrahydrofuran is used as solvent.

T. t. Mp 185-191 ° C (dec.).

c) 6-Hydroxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole

Prepared from 6-methoxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole according to general formula 7.

T. t. 216-218 [deg.] C.

6 - [[1- (3-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. Mp 115-118 ° C.

Example 30

6 - [[1- (3-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6-hydroxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to the general formula 8.

T. t. Mp 101-102 ° C.

Example 31

6 - [[1- (3-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (3-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 99-101 ° C.

Example 32

6 - [[1- (4-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 4- (5-Methoxy-2-nitrophenyl) aminobenzonitrile

A mixture of 2 g of 3-fluoro-4-nitroanisole and 15 ml of 4-aminobenzonitrile was stirred at 140 ° C for 22 hours. Then the reaction mixture was diluted with ethyl acetate, washed three times with 2 N aqueous hydrochloric acid, three times with water and once with saturated sodium chloride solution. After drying over sodium sulfate, the solvent is evaporated in vacuo and the residue is chromatographed on silica gel.

1 H-NMR (CDCl 3): δ (ppm): 3.70 s (3H); 6.38 dd (J = 8.2 Hz, 1H); 6.68 d (J = 2Hz, 1 H); 7.27 d (J = 8Hz, 2H); 7.54 d (J = 8Hz, 2H); 8.08 d (J = 8Hz, 1H); 9.60 with br (1H).

b) 6-Methoxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole

It is obtained by hydrogenation of 4- (5-methoxy-2-nitrophenyl) aminobenzonitrile according to general formula 1 and subsequent cyclization with triethyl orthobenzoate according to general regulation 3. Unlike the cyclization procedure, tetrahydrofuran is used as the solvent.

1 H-NMR (CDCl 3): δ (ppm): 3.82 s (3H); 6.72 d (J = 2Hz, 1 H); 7.00 dd (J = 8.2 Hz, 1H); 7.30-7.49 m (7H); 7.78 d (J = 8Hz, 1H); 7.81 d (J = 8Hz, 2Η).

c) 6-Hydroxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole

Prepared from 6-methoxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole according to general formula 7.

T. t. Mp 266-268 ° C.

6 - [[1- (4-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. Mp 145-148 ° C.

Example 33

6 - [[1- (4-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by the reaction of 6-hydroxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

T. t. Mp 102-103 ° C.

Example 34

6 - [[1- (3-Chloro-phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 1- (3-Chlorophenyl) -6-methoxy-2-phenyl-1H-benzimidazole

Prepared by reduction of (3-chlorophenyl) - (5-methoxy-2-nitrophenyl) -amine (Belton, McClnemey, Proc. R. Ir. Acad. Sect. B, 69, 21,27 (1970)) according to general formula 2 followed by cyclisation with triethyl orthobenzoate according to general rule 3.

T. t. Mp 140-143 ° C.

b) 1- (3-Chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole

Prepared from 6-methoxy-1- (3-chlorophenyl) -2-phenyl-1H-benzimidazole according to general formula 6.

T. t. 210-214 ° C.

6 - [[1- (3-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 1- (3-chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. 101-105 ° C.

Example 35

6 - [[1- (3-Chloro-phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reacting 1- (3-chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to General Regulation 8.

T. t. Mp 107-112 ° C.

Example 36

6 - [[1- (3-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Obtained from 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.36-1.78 m (6H); 2.24 t (J = 7.5Hz, 2H); 3.96 t (J = 7.5Hz, 2H); 6.68 d (J = 2Hz, 1 H); 6.97 dd (J = 8.2 Hz, 1H); 7.32-7.65 m (9H); 7.69 d (J = 8Hz, 1 H).

Example 37

6 - [[1- (3-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol

Obtained from 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.38-1.88 m (8H); 3.67 t (J = 7.5Hz, 2H); 3.96 t (J = 7.5Hz, 2H); 6.70 d (J = 2Hz, 1H); 6.97 dd (J = 8.2 Hz, 1H); 7.18 ddd (J = 8.2,2Hz, 1H); 7.25-7.55 m (8H); 7.76 d (J = 8Hz, 1 H).

Example 38

6 - [[1- (4-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 1- (4-Chlorophenyl) -6-methoxy-2-phenyl-1H-benzimidazole

It is prepared by reduction of (4-chlorophenyl) - (5-methoxy-2-nitro-phenyl) amine (Kottenhahn et al., J. Org. Chem. 28, 3114, 3118 (1963)) according to general formula 2 followed by cyclization with triethyl orthobenzoate according to General Regulation 3.

1 H-NMR (CDCl 3): δ (ppm): 3.82 s (3H); 6.67 d (J = 2Hz, 1 H); 6.97 dd (J = 8.2 Hz, 1H); 7.22-7.40 m (5H); 7.46-7.55 m (4H); 7.77 d (J = 8Hz, 1 H).

b) 1- (4-Chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole

Prepared from 1- (4-chlorophenyl) -6-methoxy-2-phenyl-1H-benzimidazole according to general formula 6. 1 H-NMR (d 6 -DMSO): δ (ppm): 6.60 d (J = 2) Hz, 1H); 6.87 dd (J = 8.2 Hz, 1H); 7.40-7.56 m (7H); 7.64 d (J = 8Hz, 1H); 7.70 d (J = 8Hz, 2H); 9.50 with br (1H).

6 - [[1- (4-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by the reaction of 1- (4-chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to General Regulation 8.

T. t. Mp 100-104 ° C.

Example 39

6 - [[1- (4-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by the reaction of 1- (4-chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to General Regulation 8.

T. t. Mp 83-88 ° C.

Example 40

6 - [[1- (4-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Obtained from 6 - [[1- (4-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.35-1.78 m (6H); 2.25 t (J = 7.5Hz, 2H); 3.94 t (J = 7.5Hz, 2H); 6.68 d (J = 2Hz, 1 H); 6.95 dd (J = 8.2Hz, 1H); 7.33-7.54 m (7H); 7.63 d (J = 8Hz, 2H); 7.69 d (J = 8Hz, 1 H).

Example 41

6 - [[1- (4-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol

Obtained from 6 - [[1- (4-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

T. t. Mp 115-120 ° C.

Example 42

6 - [[1- (2-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 5-Chloro-2-nitrophenyl-o-tolylamine

To a solution of 10 g of 1-chloro-3,4-dinitrobenzene in 50 ml of ethanol is added 81 ml of o-toluidine and heated at reflux for 72 hours. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and 2 N aqueous hydrochloric acid. The organic phase is washed three more times with 2 N aqueous hydrochloric acid, dried over sodium sulphate and evaporated in vacuo. The residue was purified by silica gel chromatography.

1 H-NMR (CDCl 3): δ (ppm): 2.28 s (3H); 6.70 dd (J = 10.2 Hz, 1H); 6.80 d (J = 2Hz, 1 H); 7.22-7.40 m (4H); 8.18 d (J = 10Hz, 1H); 9.40 with br (1H).

b) 5-Methoxy-2-nitrophenyl-o-tolylamine

To a solution of 1 g of sodium in 20 ml of methanol was added 1 g of 5-chloro-2-nitrophenyl-o-tolylamine and the mixture was refluxed for 72 hours. It is then cooled to 0 ° C and the crystalline product is filtered off with suction.

1 H-NMR (CDCl 3): δ (ppm): 2.30 s (3H); 3.72 s (3H); 6.19 d (J = 2Hz, 1 H); 6.32 dd (J = 10.2 Hz, 1H); 7.20-7.40 m (4H); 8.20 d (J = 10 Hz, 1H); 9.62 with br (1H).

c) 6-Methoxy-1- (2-methylphenyl) -2-phenyl-1H-benzimidazole

It is prepared from 5-methoxy-2-nitrophenyl-o-tolylamine according to general formula 1 and subsequent cyclization with triethyl orthobenzoate according to general regulation 3.

1 H-NMR (CDCl 3): δ (ppm): 1.93 s (3H); 3.78 s (3H); 6.42 d (J = 2Hz, 1 H); 6.97 dd (J = 8.2 Hz, 1H); 7.22-7.48 m (7H); 7.57 dd (J = 8.1 Hz, 2H); 7.78 d (J = 8Hz, 1 H).

6- [[1- (2-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6-Methoxy-1- (2-methylphenyl) -2-phenyl-1H-benzimidazole Allow to react according to General Regulation 6.

The crude product is reacted with 6-bromohexanoic acid methyl ester according to general formula 8.

1 H-NMR (CDCl 3): δ (ppm): 1.43-1.58 m (2H); 1.62-1.84 m (4H); 1.93 s (3H); 2.34 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.90 t (J = 7.5Hz, 2H); 6.42 d (J = 2Hz, 1 H); 6.96 dd (J = 8.2 Hz, 1H); 7.22-7.48 m (7H); 7.56 dd (J = 8,

1.5 Hz, 2H); 7.76 d (J = 8Hz, 1 H).

Example 43

6 - [[1- (2-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (2-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 198-200 ° C.

Example 44

6 - [[1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 5-Chloro-2-nitrophenyl-n-tolylamine

To a solution of 50 g of 1-chloro-3,4-dinitrobenzene in 250 ml of ethanol is added 81 ml of n-toluidine and the solution is allowed to stand for 72 hours. The reaction mixture was then filtered and the crystalline solid was washed with cold ethanol and 2 N aqueous hydrochloric acid. The product was purified by silica gel chromatography.

1 H-NMR (CDCl ₃ ): δ (ppm): 2.40 s (3H); 6.72 dd (J = 10.2 Hz, 1H); 7.04-7.13 m (3H); 7.14 d (J = 2Hz, 1 H); 7.32 t (J = 10Hz, 1 H); 8.18 d (J = 10Hz, 1H); 9.52 with br (1H).

b) 5-Methoxy-2-nitrophenyl-n-tolylamine

To a solution of 9 g of sodium in 670 ml of methanol was added 39 g of 5-chloro-2-nitrophenyl-n-tolylamine, and the mixture was heated under reflux for 72 hours. It is then cooled to 0 ° C and the crystalline product is filtered off with suction.

1 H-NMR (CDCl 3): δ (ppm): 2.40 s (3H); 3.73 s (3H); 6.33 dd (J = 10.2 Hz, 1H); 6.58 d (J = 2Hz, 1 H); 7.03-7.15 m (3H); 7.311 (J = 10Hz, 1H); 8.19 d (J = 10Hz, 1H); 9.72 with br (1H).

c) 6-Methoxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole

Prepared from 5-methoxy-2-nitrophenyl-n-tolylamine according to general formula 1 and subsequent cyclisation with triethyl orthobenzoate according to general formula 3.

1 H-NMR (CDCl 3): δ (ppm): 2.42 s (3H); 3.81 s (3H); 6.69 d (J = 2Hz, 1 H); 7.03 dd (J = 8.2 Hz, 1H); 7.10-7.18 m (2H); 7.30-7.48 m (5H); 7.62 dd (J = 8.1 Hz, 2H); 7.89 d (J = 8Hz, 1 H).

d) 6-Hydroxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole

Prepared from 6-methoxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole according to general formula 6.

1 H-NMR (d 6 -DMSO): δ (ppm): 2.34 s (3H); 6.52 d (J = 2Hz, 1 H); 6.80 dd (J = 8.2 Hz, 1H); 7.15 d (J = 8Hz, 1H); 7.28 with br (1H); 7.32-7.55 m (7H); 7.59 d (J = 8Hz, 1H); 9.37 with br (1H).

6 - [[1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

1 H-NMR (CDCl 3): δ (ppm): 1.44-1.58 m (2H); 1.64-1.85 m (4H); 2.35 t (J = 7.5Hz, 2H); 2.40 s (3H); 3.68 s (3H); 3.95 t (J = 7.5Hz, 2H); 6.70 d (J = 2Hz, 1H); 6.96 dd (J = 8.2 Hz, 1H); 7.10 d (J = 8Hz, 1H); 7.16 with br (2H); 7.25-7.43 m (4H); 7.55 dd (J = 8.1 Hz, 2H); 7.77 d (J = 8Hz, 1 H).

Example 45

6 - [[1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by the reaction of 6-hydroxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.22 d (J = 8 Hz, 6H); 1.44 to 1.56 m (2H, _CH2); 1.64 to 1.84 m (4H, _CH2); 2.30 t (J = 7.5Hz, 2H); 2.41 s (3H); 3.95 t (J = 7.5Hz, 2H); 5.00 sp (J = 8Hz, 1 H); 6.68 d (J = 2Hz, 1 H); 6.96 dd (J = 8.2 Hz, 1H); 7.10 d (J = 8Hz, 1H); 7.14 with br (1H); 7.25-7.41 m (4H); 7.54 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8Hz, 1H).

Example 46

6 - [[1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.38-1.80 m (6H); 2.23 t (J = 7.5Hz, 2H); 3.84-3.93 m (2H); 6.60 d (J = 2Hz, 1 H); 6.87 d br (J = 8Hz, 1H); 7.15 d (J = 8Hz, 2H); 7.20-7.32 m (4H); 7.42-7.50 m (2 H); 7.59 d (J = 8Hz, 1H); 7.77 d (J = 8Hz, 1 H).

Example 47

6 - [[1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol

Prepared from 6 - [[1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

1 H-NMR (CDCl 3): δ (ppm): 1.40-1.85 m (8H); 2.40 s (3H); 3.68 t (J = 7.5Hz, 2H); 3.96 t (J = 7.5Hz, 2H);

6.69 d (J = 1.5 Hz, 1H); 6.96 dd (J = 8, 1.5 Hz, 1H); 7.10 d (J = 8Hz, 1H); 7.13 with br (1H); 7.25-7.42 m (5H); 7.54 dd (J = 8.1 Hz, 2H); 7.76 d (J = 8Hz, 1 H).

Example 48

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 5-Chloro-2-nitrophenyl-p-tolylamine

Prepared in analogy to 5-chloro-2-nitrophenyl-n-tolylamine from 1-chloro-3,4-dinitrobenzene and p-toluidine and purified by crystallization.

1 H-NMR (CDCl ₃ ): δ (ppm): 2.40 s (3H); 6.70 dd (J = 10.2 Hz, 1H); 7.08 d (J = 2Hz, 1 H); 7.16 d (J = 10Hz, 2H); 7.28 d (J = 10Hz, 2H); 8.18 d (J = 10Hz, 1H); 9.50 with br (1H).

b) 5-Methoxy-2-nitrophenyl-p-tolylamine

Prepared in an analogous manner to 5-methoxy-2-nitrophenyl-m-tolylamine from 5-chloro-2-nitrophenyl-p-tolylamine and sodium methanolate.

1 H-NMR (CDCl 3): δ (ppm): 2.39 s (3H); 3.72 s (3H); 6.31 dd (J = 10.2 Hz, 1H); 6.50 d (J = 2Hz, 1 H); 7.19 d (J = 10Hz, 2H); 7.25 d (J = 10Hz, 2H); 8.19 d (J = 10Hz, 1H); 9.70 with br (1H).

c) 6-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

It is prepared from 5-methoxy-2-nitrophenyl-p-tolylamine according to general formula 1 and subsequent cyclization with triethyl ortho-benzoate according to general regulation 3.

1 H-NMR (CDCl 3): δ (ppm): 2.49 s (3H); 3.80 s (3H); 6.69 d (J = 2Hz, 1 H); 6.97 dd (J = 8.2 Hz, 1H); 7.20 d br (J = 8Hz, 2H); 7.25-7.36 m (5H); 7.53 dd (J = 8.1 Hz, 2H); 7.76 d (J = 8Hz, 1 H).

d) 6-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

Prepared from 6-methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole according to general formula 6.

1 H-NMR (d 6 -DMSO): δ (ppm): 2.40 s (3H); 6.50 d (J = 2Hz, 1 H); 6.80 dd (J = 8.2 Hz, 1H); 7.28 d (J = 8Hz, 2H); 7.32-7.43 m (5H); 7.46-7.52 m (2H); 7.56 d (J = 8Hz, 1H); 9.28 with br (1H).

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole and 6-bromohexanoic acid methyl ester according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.44-1.58 m (2H); 1.62-1.86 m (4H); 2.34 t (J = 7.5Hz, 2H); 2.48 s (3H); 3.68 s (3H); 3.94 t (J = 7.5Hz, 2H); 6.69 d (J = 2Hz, 1 H); 6.96 dd (J = 8.2 Hz, 1H); 7.19 d (J = 8Hz, 2H); 7.28-7.38 m (5H); 7.55 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8Hz, 1H).

Example 49

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by the reaction of 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

1 H-NMR (CDCl 3): δ (ppm): 1.22 d (J = 7.5 Hz, 6H); 1.44-1.56 m (2 H); 1.62-1.85 m (4H); 2.30 t (J = 7.5Hz, 2H); 2.47 s (3H); 3.93 t (J = 7.5Hz, 2H); 5.01 sp (J = 7.5Hz, 1H); 6.68 d (J = 2Hz, 1 H); 6.96 dd (J = 8.2 Hz, 1H); 7.20 d (J = 8Hz, 2H); 7.26-7.36 m (5H); 7.55 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8Hz, 1H).

Example 50

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Obtained from 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 186-190 ° C.

Example 51

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol

Obtained from 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

1 H-NMR (CDCl 3): δ (ppm): 1.38-1.80 m (8H); 2.47 s (3H); 3.65 t (J = 7.5Hz, 2H); 3.93 t (J = 7.5Hz, 2H); 6.68 d (J = 2Hz, 1 H); 6.97 dd (J = 8.2 Hz, 1H); 7.18 d (J = 8Hz, 2H); 7.24-7.37 m (5H); 7.54 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8Hz, 1H).

Example 52

6 - [[1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (3,4-Dimethylphenyl) amino-4-nitrophenol

A mixture of 3 g of 3-fluoro-4-nitrophenol and 6.9 g of 3,4-dimethylaniline is stirred for 2 hours at 150 ° C. After cooling, the reaction mixture was dissolved in dichloromethane and extracted six times with 1 N aqueous hydrochloric acid. The organic phase is discarded and the combined aqueous phases are extracted three times with chloroform. The combined extracts were dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

1 H-NMR (CDCl ₃ / d ₆ -DMSO): δ (ppm): 2.18 s (6H); 6.13 dd (J = 8.2 Hz, 1H); 6.36 d (J = 2Hz, 1 H); 6.90-7.00 m (2H); 7.09 d (J = 8Hz, 1H); 7.93 d (J = 8Hz, 1H); 9.50 with br (1H); 10.19 with br (1H).

b) 6- [3- (3,4-Dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester

It is prepared by reacting 3- (3,4-dimethylphenyl) amino-4-nitrophenol with methyl 6-bromohexanoate according to general formula 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.38-1.52 m (2H); 1.59-1.80 m (4H); 2.30 s (6H); 2.33 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.87 t (J = 7.5Hz, 2H); 6.28 dd (J = 8.2 Hz, 1H); 6.48 d (J = 2Hz, 1 H); 7.04 d (J = 8Hz, 1H); 7.06 with br (1H); 7.18 d (J = 8Hz, 1H); 8.17 d (J = 8Hz, 1H); 9.71 with br (1H).

6 - [[1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Obtained from methyl 6- [3- (3,4-dimethylphenyl) amino-4-nitrophenyl] oxyhexanoate according to general formula 1, followed by cyclization with triethyl orthobenzoate according to general formula 3.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.44-1.56 m (2H); 1.62-1.84 m (4H); 2.30 s (3H); 2.33 t (J = 7.5Hz, 2H); 2.34 s (3H); 3.68 s (3H); 3.93 t (J = 7.5Hz, 2H); 6.67 d (J = 2Hz, 1 H); 6.94 dd (J = 8.2 Hz, 1H); 7.03 dd (J = 8, 1.5 Hz, 1H); 7.09 with br (1H); 7.22-7.35 m (4H); 7.57 dd (J = 8.1.5 Hz, 2H); 7.76 d (J = 8Hz, 1 H).

Example 53

6 - [[1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 158-161 ° C.

Example 54

6 - [[1- (3,5-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (3,5-Dimethylphenyl) amino-4-nitrophenol

A mixture of 5.4 g of 3-fluoro-4-nitrophenol and 4.3 ml of 3,5-dimethylaniline was stirred at 120 ° C for 6 hours. After cooling, the reaction mixture was partitioned between ethyl acetate and water, and the organic layer was extracted three times with 1 N aqueous hydrochloric acid. The combined aqueous phases are extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulphate, concentrated in vacuo and the residue is crystallized.

1 H-NMR (d 6 -DMSO): δ (ppm): 2.30 s (6H); 6.28 dd (J = 8.2 Hz, 1H); 6.49 d (J = 2Hz, 1 H); 6.52 d (J = 2Hz, 1 H); 6.90 with br (1H); 6.98 with br (2H); 8.04 d (J = 8Hz, 1H); 9.51 with br (1H).

b) 6- [3- (3,5-Dimethylphenyl) amino-4-nitro-phenyl] oxyhexanoic acid methyl ester

Prepared by the reaction of 3- (3,5-dimethylphenyl) amino-4-nitrophenol with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.40-1.52 m (2H); 1.60-1.80 m (4H); 2.301 (J = 7.5Hz, 2H); 2.32 s (6H); 3.68 s (3H); 3.88 t (J = 7.5Hz, 2H); 6.30 dd (J = 8.2 Hz, 1H); 6.52 d (J = 2Hz, 1 H); 6.88 with br (1H); 6.91 with br (2H); 8.17 d (J = 8Hz, 1H); 9.69 with br (1H).

6 - [[3- (3,5-Dimethylphenyl) -amino-4-nitrophenyl] oxy] hexanoic acid methyl ester

Prepared from 6- [3- (3,5-dimethylphenyl) amino-4-nitrophenyl] oxy-hexanoic acid methyl ester according to general formula 1, followed by cyclization with triethyl orthobenzoate according to general formula 3.

T. t. Mp 124-126 ° C.

Example 55

6 - [[1- (3,5-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Obtained from 6 - [[3- (3,5-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 162-164 ° C.

Example 56

6 - [[1- (3,5-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reacting 6 - [[3- (3,5-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid with isopropanol according to the general formula 10.

T. t. Mp 98-101 ° C.

Example 57

6 - [[1- (3-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (3-Methoxyphenyl) amino-4-nitrophenol

A mixture of 4 g of 3-fluoro-4-nitrophenol and 9.4 g of n-anisidine was stirred at 150 ° C for 2.5 hours. After cooling, the reaction mixture was dissolved in dichloromethane and extracted three times with 1 N aqueous hydrochloric acid. The organic phase is dried over sodium sulphate, concentrated in vacuo and the residue is chromatographed on silica gel.

1 H-NMR (CDCl 3): δ (ppm): 3.83 s (3H); 6.30 dd (J = 10.2 Hz, 1H); 6.57 d (J = 2Hz, 1 H); 6.70-6.84 m (2H); 6.89 dbr (J = 10Hz, 1H); 7.32 t (J = 10Hz, 1 H); 8.19 d (J = 10Hz, 1H); 9.68 with br (1H); 9.69 with br.

b) 6- [3- (3-Methoxyphenyl) amino-4-nitro-phenyl] oxyhexanoic acid methyl ester

Prepared by the reaction of 3- (3-methoxyphenyl) amino-4-nitrophenol with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.42-1.58 m (2H); 1.60-1.93 m (4H); 2.34 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.80 s (3H); 4.03 t (J = 7.5Hz, 2H); 6.32 dd (J = 10.2 Hz, 1H); 6.59 d (J = 2Hz, 1 H); 6.68-6.84 m (2H); 6.90 d br (J = 8Hz, 1H); 7.32 t (J = 8Hz, 1H); 8.19 d (J = 10Hz, 1H); 9.70 with br (1H).

6 - [[1- (3-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from 6- [3- (3-methoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester according to general formula 1, followed by cyclization with triethyl orthobenzoate according to general formula 3.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.44-1.58 m (2H); 1.62-1.86 m (4H); 2.34 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.78 s (3H); 3.95 t (J = 7.5Hz, 2H); 6.71 d (J = 1.5 Hz, 1H); 6.83 dd (J = 1.5, 1.5 Hz, 1H); 6.90 dd (J = 8, 1.5 Hz, 1H); 6.94 dd (J = 8, 1.5 Hz, 1H); 7.01 dd (J = 8.1.5 Hz, 1H); 7.27-7.36 m (3H); 7.401 (J = 8.1 H); 7.56 dd (J = 8.2 Hz, 2H); 7.74 d (J = 8Hz, 1H).

Example 58

6 - [[1- (3-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Prepared from 6 - [[1- (3-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 149-152 ° C.

Example 59

6 - [[1- (4-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (4-Methoxyphenyl) amino-4-nitrophenol

A mixture of 0.16 g of 3-fluoro-4-nitrophenyl and 0.37 g of p-anisidine was stirred at 150 ° C for 1.5 hours. After cooling, the reaction mixture was dissolved in dichloromethane, extracted twice with 1 N aqueous hydrochloric acid and once with saturated sodium chloride solution. The organic phase is dried over sodium sulphate and concentrated in vacuo.

1 H-NMR (CDCl 3 / d 6 -DMSO): δ (ppm): 3.57 s (3H); 6.06 dd (J = 10.2 Hz, 1H); 6.18 d (J = 2Hz, 1 H); 6.77 d (J = 10Hz, 2H); 7.03 d (J = 10Hz, 2H); 7.89 d (J = 10Hz, 1H); 9.40 with br (1H); 9.80 with br.

b) 6- [3- (4-Methoxyphenyl) amino-4-nitro-phenyl] oxyhexanoic acid methyl ester

Prepared by the reaction of 3- (4-methoxyphenyl) amino-4-nitrophenol with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.38-1.50 m (2H); 1.60-1.80 m (4H); 2.33 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.85 t (J = 7.5Hz, 2H); 3.88 s (3H); 6.29 dd (J = 10, 1.5 Hz, 1H); 6.30 d (J = 1.5 Hz, 1H); 6.98 d (J = 10Hz, 2H); 7.20 d (J = 10Hz, 2H); 8.18 d (J = 10Hz, 1H); 9.63 with br (1H).

6 - [[1- (4-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from methyl 6- [3- (4-methoxyphenyl) amino-4-nitrophenyl] oxyhexanoate according to general formula 1, followed by cyclization with triethyl orthobenzoate according to general formula 3.

T. t. Mp 98-102 ° C.

Example 60

6 - [[1- (4-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 160-165 ° C.

Example 61

6 - [[1- (3,4-Dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (3,4-Dimethoxyphenyl) amino-4-nitrophenol

A mixture of 3 g of 3-fluoro-4-nitrophenol and 8.8 g of 3,4-dimethoxyaniline was stirred at 150 ° C for 2 hours. After cooling, the reaction mixture was dissolved in dichloromethane and extracted twice with 1 N aqueous hydrochloric acid. The aqueous phase is extracted twice with chloroform and the combined chloroform extracts are dried over sodium sulphate and concentrated in vacuo.

1 H-NMR (d 6 -DMSO): δ (ppm): 3.75 s (3H); 3.78 s (3H); 6.25 dd (J = 10.2 Hz, 1H); 6.35 d (J = 2Hz, 1 H);

6.88 dd (J = 8, 1.5 Hz, 1H); 6.98 dd (J = 1.5 Hz, 1H); 7.05 d (J = 8Hz, 1H); 8.04 d (J = 10Hz, 1H); 9.52 with br (1H); 10,72 with br.

b) 6- [3- (3,4-Dimethoxyphenyl) amino-4-nitro-phenyl] oxyhexanoic acid methyl ester

It is prepared by reacting 3- (3,4-dimethoxyphenyl) amino-4-nitrophenol with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.40-1.52 m (2H); 1.60-1.80 m (4H); 2.32 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.85 t (J = 7.5Hz, 2H); 3.88 s (3H); 3.93 s (3H); 6.29 dd (J = 10, 1.5 Hz, 1H); 6.33 d (J = 1.5 Hz, 1H); 6.80 d (J = 1.5 Hz, 1H); 6.87 dd (J = 10, 1.5 Hz, 1H); 6.92 d (J = 10Hz, 1H); 8.18 d (J = 10Hz, 1H); 9.68 sbr (1H).

6 - [[1- (3,4-Dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from 6- [3- (3,4-dimethoxyphenyl) -amino-4-nitrophenyl] oxyhexanoic acid methyl ester according to general formula 1, followed by cyclization with triethyl orthobenzoate according to general formula 3.

T. t. Mp 116-118 ° C.

Example 62

6 - [[1- (3,4-Dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from methyl 6 - [[1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 158-161 ° C.

Example 63

6 - [[1- [3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (3,4-Methylenedioxyphenyl) amino-4-nitrophenol

A mixture of 0.86 g of 3-fluoro-4-nitrophenol and 2.25 g of 3,4-methylenedioxy-aniline was stirred at 120 ° C for 5 hours. The crude reaction mixture was subjected to silica gel chromatography.

1 H-NMR (d 6 -DMSO): δ (ppm): 6.02 s (2H); 6.25 dd (J = 10.2 Hz, 1H); 6.33 d (J = 2Hz, 1 H); 6.72 dd (J = 8,

1.5 Hz, 1H); 6.87 d (J = 1.5 Hz, 1H); 7.05 d (J = 10Hz, 1H); 8.18 d (J = 10Hz, 1H); 9.52 with br (1H).

b) 6- [3- (3,4-methylenedioxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester

It is prepared by reacting 3- (3,4-methylenedioxyphenyl) amino-4-nitro-phenol with methyl 6-bromohexanoate according to general formula 8.

T. t. 108-111 ° C.

6 - [[1- (3,4-methylenedioxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from 6- [3- (3,4-methylenedioxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester according to general formula 1 and subsequent cyclization with triethyl orthobenzoate according to general formula 3.

1 H-NMR (CDCl 3): δ (ppm): 1.43-1.55 m (2H); 1.65-1.82 m (4H); 2.35 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.95 t (J = 7.5Hz, 2H); 6.10 s (2H); 6.65 d (J = 1.5 Hz, 1H); 6.72-6.83 m (2H); 6.90 d (J = 10Hz, 1H); 6.93 dd (J = 10,

1.5 Hz, 1H); 7.29-7.38 m (3H); 7.52-7.62 m (2H); 7.72 d (J = 10Hz, 1 H).

Example 64

6 [[1- [3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (3,4-methylenedioxy-phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. 130 [deg.] C.

Example 65

6 - [[2-Phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (3,4,5-Trimethoxyphenyl) amino-4-nitrophenol

A mixture of 3.7 g of 3-fluoro-4-nitrophenol and 4.76 g of 3,4,5-trimethoxy-aniline is stirred for 10 hours at 100 ° C. After cooling, the mixture was partitioned between ethyl acetate and water and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases are extracted three times with 1 N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulphate and evaporated as much as possible in vacuo. The product was digested with diisopropyl ether.

1 H-NMR (d 6 -DMSO): δ (ppm): 3.70 s (3H); 3.80 s (6H); 6.28 dd (J = 10.2 Hz, 1H); 6.53 d (J = 2Hz, 1 H);

6.70 s (2H); 8.05 d (J = 10Hz, 1H); 9.50 with br (1H); 10.71 with br.

b) 6- [4-Nitro-3 - [(3,4,5-trimethoxyphenyl) amino] phenyl] oxyhexanoic acid methyl ester

It is prepared by reacting 4-nitro-3 - [(3,4,5-trimethoxyphenyl) amino] -phenol with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.40-1.53 m (2H); 1.60-1.82 m (4H); 2.32 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.85 s (6H); 3.88 t (J = 7.5Hz, 2H); 3.90 s (3H); 6.30 dd (J = 10, 1.5 Hz, 1H); 6.50 d (J = 1.5 Hz, 1H); 6.52 s (2H);

8.18 d (J = 10Hz, 1H); 9.68 with br (1H).

6 - [[2-Phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Obtained from 6- [4-nitro-3 - [(3,4,5-trimethoxyphenyl) amino] phenyl] oxy-hexanoic acid methyl ester according to general formula 1 and subsequent cyclization with triethyl orthobenzoate according to general formula 3.

T. t. Mp 128-130 ° C.

Example 66

6 - [[2-Phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 198-201 ° C.

Example 67

6 - [[2-Phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reacting 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid with isopropanol according to the general formula 10.

T. t. 98-101 ° C.

Example 68

6 - [[1- [4- (N, N-Dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

(a) N, N-Dimethyl-N '- (5-chloro-2-nitrophenyl) benzene-1,4-diamine

Prepared in analogy to 5-chloro-2-nitrophenyl-1-tolylamine from 1-chloro-3,4-dinitrobenzene and N, N-dimethyl- (2-phenylenediamine).

1 H-NMR (CDCl 3): δ (ppm): 3.01 s (6H); 6.63 dd (J = 10.2 Hz, 1H); 6.80 d br (J = 10Hz, 2H); 6.97 d (J = 2Hz, 1 H); 7.14 d (J = 10Hz, 2H); 8.14 d (J = 10Hz, 1H); 9.42 with br (1H).

(b) N- (7-Dimethyl-7 '- (5-methoxy-2-nitrophenyl) benzene-1,4-diamine

24.9 g of N- (N-dimethyl-N '- (5-chloro-2-nitrophenyl) benzene-1,4-diamine) were added to a solution of 8 g of sodium in 200 ml of methanol and the mixture was heated to autoclave for 9 hours at 120 [deg.] C. After cooling, the crystalline product is filtered off with suction.

1 H-NMR (CDCl ₃ ): δ (ppm): 3.00 s (6H); 3.70 s (3H); 6.25 dd (J = 10.2 Hz, 1H); 6.34 d (J = 2Hz, 1 H); 6.78 d (J = 10Hz, 2H); 7.14 d (J = 10Hz, 2H); 8.16 d (J = 10Hz, 1H); 9.67 with br (1H).

c) 6-Methoxy-1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole

Prepare from N, N -dimethyl-N- (5-methoxy-2-nitrophenyl) benzene-1,4-diamine according to general formula 1, followed by reaction of the crude diamine with trimethyl orthobenzoate according to general formula 3, followed by boiling under reflux with 6 N aqueous hydrochloric acid for 1 hour. After alkalization of the reaction mixture with aqueous sodium hydroxide, the mixture is extracted with ethyl acetate, the organic phase is dried over sodium sulphate and concentrated in vacuo.

1 H-NMR (CDCl ₃ ): δ (ppm): 3.04 s (6H); 3.80 s (3H); 6.68 d (J = 2Hz, 1 H); 6.78 d (J = 10Hz, 2H); 6.95 dd (J = 10.2 Hz, 1H); 7.17 d (J = 10Hz, 2H); 7.25-7.33 m (3H); 7.56-7.64 m (2H); 7.74 d (J = 10Hz, 1 H).

d) 6-Hydroxy-1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole

Prepared from 6-methoxy-l- [4- (7V, and ^L N-dimethylamino) phenyl] -2-phenyl-lH-benzimidazole of the general procedure sixth

1 H-NMR (d 6 -DMSO): δ (ppm): 2.98 s (6H); 6.48 d (J = 2Hz, 1 H); 6.78 dd (J = 10.2 Hz, 1H); 6.83 d (J = 10Hz, 2H); 7.17 d (J = 10Hz, 2H); 7.30-7.38 m (3H); 7.50-7.57 m (3H); 9.32 with br (1H).

Methyl 6 - [[l- [4- ^(l, 7V-dimethylamino) phenyl] -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanoic acid

It is prepared by reacting 6-hydroxy-1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.43-1.57 m (2H); 1.64-1.85 m (4H); 2.33 t (J = 7.5Hz, 2H); 3.05 s (6H); 3.67 s (3H); 3.93 t (J = 7.5Hz, 2H); 6.65 d (J = 2Hz, 1 H); 6.76 d (J = 10Hz, 2H); 6.93 dd (J = 10.2 Hz, 1H); 7.14 d (J = 10Hz, 2H); 7.23-7.27 m (3H); 7.62 dd (J = 10.1, Hz, 2H); 7.74 d (J = 10Hz, 1 H).

Example 69

6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from methyl 6 - [[l- [4- (N ^s, N-dimethylamino) phenyl] -2-phenyl-lH-benzimidazol-6-yl] oxylhexánovej the general procedure ninth

T. t. 210-213 ° C.

Example 70

6 - [[1- (4-Biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 5-Chloro-2-nitrophenyl-4-biphenylamine

Prepared in analogy to 5-chloro-2-nitrophenyl- n -tolylamine from 1-chloro-3,4-dinitrobenzene and 4-biphenylamine. The product was purified by silica gel chromatography.

1 H-NMR (CDCl 3): δ (ppm): 6.76 dd (> 10.2 Hz, 1H); 7.26 d (J = 2Hz, 1 H); 7.35 d (J = 8Hz, 1H); 7.32-7.52 m (4H); 7.60-7.72 m (4H); 8.19 d (J = 10Hz, 1H); 9.60 with br (1H).

b) 5-Methoxy-2-nitrophenyl-4-biphenylamine

Prepared in analogy to 5-methoxy-2-nitrophenyl- n -tolylamine by reacting 5-chloro-2-nitrophenyl-4-biphenylamine with sodium methoxide.

T. t. Mp 150-154 ° C.

c) 1- (4-Biphenyl) -6-methoxy-2-phenyl-1H-benzimidazole

It is prepared from 5-methoxy-2-nitrophenyl-4-biphenylamine according to general formula 1 and subsequent cyclisation with triethyl orthobenzoate according to general regulation 3.

T. t. Mp 140-144 ° C.

d) 1- (4-Biphenyl) -6-hydroxy-2-phenyl-1H-benzimidazole

Prepared from 1- (4-biphenyl) -6-methoxy-2-phenyl-1H-benzimidazole according to general formula 6.

T. t. 312 ° C.

6 - [[1- (4-Biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by the reaction of 1- (4-biphenyl) -6-hydroxy-2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to General Regulation 8.

T. t. 106-108 ° C.

Example 71

6 - [[1- (4-Biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (4-biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.35-1.78 m (6H); 2.20 t (J = 7.5Hz, 2H); 3.96 m (2H); 6.72 d (J = 2Hz, 1 H); 6.97 dd (> 10, 2 Hz, 1H); 7.32-7.58 m (10H); 7.69 d (J = 10Hz, 1H); 7.80 d (J = 8Hz, 2H); 7.89 d (J = 10Hz, 2H).

Example 72

6 - [[1- (2-Naphthyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (2-Naphlamino) -4-nitrophenol

A mixture of 3 g of 3-fluoro-4-nitrophenol and 8.2 g of 2-naphthylamine was stirred at 180 ° C for 8 hours. The crude mixture was dissolved in chloroform and washed with 2 N aqueous hydrochloric acid. The organic phase is dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (d 6 -DMSO): δ (ppm): 6.02 s (2H); 6.25 dd (> 10, 2 Hz, 1H); 6.33 d (J = 2Hz, 1 H); 6.72 dd (J = 8,

1.5 Hz, 1H); 6.87 d (J = 1.5 Hz, 1H); 7.05 d (J = 10Hz, 1H); 8.18 d (> 10 Hz, 1H); 9.52 with br (1H).

b) 6- [3- (2-Naphthyl) amino-4-nitrophenyl] oxy-hexanoic acid methyl ester

It is prepared by reacting 3- (2-naphthylamino) -4-nitrophenol with 6-bromohexanoic acid methyl ester as described in General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.35-1.49 m (2H); 1.60-1.80 m (4H); 2.30 t (J = 7.5Hz, 2H); 3.64 s (3H); 3.84 t (J = 7.5Hz, 2H); 6.35 dd (> 10, 2 Hz, 1H); 6.62 d (> 2 Hz, 1H); 7.43 dd (J = 10.2 Hz, 1H); 7.48-7.57 m (2H); 7.75 d (J = 2Hz, 1 H); 7.78-7.90 m (2H); 7.91 d (J = 10Hz, 1H); 8.21 d (> 10 Hz, 1H); 9.92 with br (1H).

6 - [[1- (2-Naphthyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from methyl 6- [3- (2-naphthyl) amino-4-nitrophenyl] oxyhexanoate according to general formula 1, followed by cyclisation with triethyl orthobenzoate according to general formula 3.

T. t. Mp 111-111 ° C.

Example 73

6 - [[1- (2-Naphthyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[1- (2-naphthyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester as described in General Regulation 9.

Mp 1.170-175 ° C.

Example 74

6 - [[1- (2-Fluorenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 3- (2-Fluorenylamino) -4-nitrophenol

A mixture of 2.17 g of 3-fluoro-4-nitrophenol and 5 g of 2-aminofluorene was stirred at 140 ° C for 9 hours. The crude reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with 1 N aqueous hydrochloric acid. The aqueous phase is extracted with ethyl acetate, the combined organic phases are washed 3x with 2 N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel.

1 H-NMR (d 6 -DMSO): δ (ppm): 3.96 s (2H); 6.30 dd (J = 10.2 Hz, 1H); 6.52 d (J = 2Hz, 1 H); 7.28-7.45 m (3H); 7.57 with br (1H); 7.60 d (J = 8Hz, 1H); 7.92 d (J = 8Hz, 1H); 7.98 d (J = 8Hz, 1H); 8.10 d (J = 10Hz, 1H);

9.70 s (1H); 10.80 with br (1H).

b) 6- [3- (2-Fluorenylamino) -4-nitrophenyl] oxyhexanoic acid methyl ester

It is prepared by reacting 3- (2-fluorenylamino) -4-nitrophenol with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.38-1.50 m (2H); 1.58-1.80 m (4H); 2.301 (J = 7.5Hz, 2H); 3.65 s (3H); 3.84 t (J = 7.5Hz, 2H); 3.95 s (2H); 6.31 dd (J = 10.2 Hz, 1H); 6.53 d (J = 2Hz, 1 H); 7.33 t (J = 8Hz, 2H); 7.42 t (J = 8Hz, 1H); 7.47 s (1H); 7.58 d (J = 8Hz, 1H); 7.80 d (J = 8Hz, 1H); 7.83 d (J = 8Hz, 1H); 8.21 d (J = 10Hz, 1H);

9.87 with br (1H).

6 - [[1- (2-Fluorenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepare from methyl 6- [3- (2-fluorenylamino) -4-nitrophenyl] oxyhexanoate according to general formula 1 and then cyclize with triethyl orthobenzoate according to general formula 3.

T. t. Mp 125-128 ° C.

Example 75

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) Ethyl (3-trifluoromethyl) benzimidate hydrochloride

A solution of 9.7 mL of 3- (trifluoromethyl) benzonitrile in 12 mL of ethanol was saturated with hydrogen chloride gas while cooling in an ice bath. After 72 hours, the precipitated product is filtered off with suction and washed with diethyl ether.

T. t. 131-133 ° C (dec.).

b) 5-Methoxy-2-nitrophenyldiphenylamine

A solution of 2 g of 3-fluoro-4-nitroanisole in 16 ml of aniline was stirred at 140 ° C for 24 hours. After cooling, the reaction mixture was diluted with ethyl acetate and extracted with 2 N aqueous hydrochloric acid. The organic phase is dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (CDCl 3): δ (ppm): 3.72 s (3H); 6.36 dd (J = 10.2 Hz, 1H); 6.57 d (J = 2Hz, 1 H); 7.22-7.33 m (3H); 7.44 dd (J = 8.8 Hz, 2H); 8.18 d (J = 10Hz, 1H); 9.78 with br (1H).

c) 4-Methoxy-N'-phenyl-o-phenylenediamine

Prepared from 5-methoxy-2-nitrophenyldiphenylamine according to General Regulation 1.

1 H-NMR (CDCl 3): δ (ppm): 3.42 s br (2H); 3.72 s (3H); 5.33 with br (1H); 6.56 dd (J = 10.2 Hz, 1H); 6.76 d (J = 10Hz, 1H); 6.79 d (J = 2Hz, 1 H); 6.82-6.90 m (3H); 7.25 dd (J = 8.8 Hz, 2H).

d) 6-Methoxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole

Prepared by reaction of 4-methoxy-N ^2- phenyl-o-phenylenediamine with ethyl (3-trifluoromethyl) benzimidate hydrochloride according to general formula 4.

T. t. 138-140 ° C.

e) 6-Hydroxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole

Prepared from 6-methoxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole according to general formula 7.

1 H-NMR (d 6 -DMSO): δ (ppm): 6.60 d (J = 2 Hz, 1H); 6.99 dd (J = 10.2 Hz, 1H); 7.50-7.89 m (10H).

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. Mp 68-70 ° C.

Example 76

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6-hydroxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

T. t. 96-98 ° C.

Example 77

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid

From methyl 6 - [[1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.38-1.80 m (6H); 2.27 t (J = 7.5Hz, 2H); 3.98 t (J = 7.5Hz, 2H); 6.70 d (J = 2Hz, 1H); 7.02 dd (J = 10.2Hz, 1H); 7.48-7.88 m (9H); 7.77 d (J = 10Hz, 1H); 11.94 with br (1H).

Example 78

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexan-1-ol

Prepared from 6 - [[1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

1 H-NMR (CDCl 3): δ (ppm): 1.38-1.68 m (6H); 1.75-1.87 m (2H); 3.60-3.72 m (2H); 3.94 t (J = 7.5Hz, 2H); 6.69 d (J = 2Hz, 1 H); 6.99 dd (J = 10.2 Hz, 1H); 7.25-7.35 m (2H); 7.40 dd (J = 8.8 Hz, 1H); 7.50-7.61 m (4H); 7.68 d br (J = 8Hz, 1H); 7.78 d (J = 10Hz, 1H); 7.83 with br (1H).

Example 79

6 - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 2- (3-Chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole

It is prepared by reacting 4-methoxy- _N ² -phenyl-o-phenylenediamine with ethyl 3-chlorobenzimidate hydrochloride (prepared according to DeWolf and Augustine, J. Org. Chem. 30, 699) according to general formula 4.

T. t. Mp 149-151 ° C.

b) 2- (3-Chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole

Prepared from 2- (3-chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole according to the general formula 7.

T. t. Mp 199-202 ° C.

6 - [[2- (3-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reacting 2- (3-chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to General Regulation 8.

T. t. Mp 69-72 ° C.

Example 80

6 - [[2- (3-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reacting 2- (3-chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole with 6-bromo-hexanoic acid isopropyl ester according to General Regulation 8.

T. t. 98-100 ° C.

Example 81

6 - [[2- (3-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Obtained from 6 - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 137-140 ° C.

Example 82

6 - [[2- (3-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol

Obtained from 6 - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

1 H-NMR (CDCl 3): δ (ppm): 1.40-1.70 m (6H); 1.75-1.86 m (2H); 3.67 t (J = 7.5Hz, 2H); 3.93 t (J = 7.5Hz, 2H); 6.69 d (J = 2Hz, 1 H); 6.99 dd (J = 10.2 Hz, 1H); 7.20 dd (J = 8.8 Hz, 1H); 7.26-7.38 m (4H); 7.47-7.58 m (3H); 7.60 dd (J = 2.2 Hz, 1H); 7.76 d (J = 10Hz, 1 H).

Example 83

6 - [[2- (4-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) Ethyl 4-chlorobenzimidate hydrochloride g 4-chlorobenzonitrile is suspended in 12 ml of ethanol and diethyl ether is added until dissolution. The solution was saturated with hydrogen chloride gas while cooling in an ice bath. After 72 hours, the precipitated product is filtered off with suction and washed with diethyl ether.

T. t. Mp 173-174 ° C (dec.).

a) 2- (4-Chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole

It is prepared by reacting 4-methoxy- N ² -phenyl-o-phenylenediamine with ethyl 4-chlorobenzimidate hydrochloride according to general formula 4.

T. t. Mp 162-164 ° C.

b) 2- (4-Chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole

Prepared from 2- (4-chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole according to the general formula 7.

T. t. Mp 246-250 ° C.

6 - [[2- (4-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reacting 2- (4-chlorophenyl) -6-hydroxy-1-phenyl-benz-benzimidazole with 6-bromohexanoic acid methyl ester according to General Regulation 8.

T. t. Mp 86-87 ° C.

Example 84

6 - [[2- (4-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reacting 2- (4-chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole with 6-bromo-hexanoic acid isopropyl ester according to General Regulation 8.

T. t. Mp 124-126 ° C.

Example 85

6 - [[2- (4-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Obtained from 6 - [[2- (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.35-1.48 m (2H); 1.50-1.62 m (2H); 1.64-1.77 m (2H); 2.23 t (J = 7.5Hz, 2H); 3.91 t (J = 7.5Hz, 2H); 6.64 d (J = 2Hz, 1 H); 6.96 dd (J = 10.2 Hz, 1H); 7.38-7.50 m (6H); 7.52-7.65 m (3H); 7.70 d (J = 10Hz, 1H).

Example 86

6 - [[2- (4-Chloro-phenyl) -l-phenyl-lH-benzimidazol-6-yl] oxy] hexan-l-ol

Obtained from 6 - [[2- (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 11.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.38-1.68 m (6H); 1.74-1.85 m (2H); 3.67 t br (J = 7.5Hz, 2H); 3.94 t (J = 7.5Hz, 2H); 6.68 dd (J = 2Hz, 1H); 6.98 dd (J = 10.2 Hz, 1H); 7.22-7.35 m (5H); 7.47 d (J = 8 Hz, 2H); 7.49-7.59 m (2H); 7.73 d (J = 10Hz, 1 H).

Example 87

6 - [[2- (3-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 6-Methoxy-2- (3-methylphenyl) -1-phenyl-1H-benzimidazole

It is prepared by reacting 4-methoxy-N ^2- phenyl-o-phenylenediamine with ethyl 3-methylbenzimidate hydrochloride (prepared according to: DeWolfe and Augustine, J. Org. Chem. 30, 699) according to general formula 4.

T. t. Mp 156-158 ° C.

b) 6-Hydroxy-2- (3-methylphenyl) -1-phenyl-1H-benzimidazole

Prepared from 6-methoxy-2- (3-methylphenyl) -1-phenyl-ΙΗ-benzimidazole according to general formula 7. 1 H-NMR (d 6 -DMSO): δ (ppm): 2.23 s (3H); 6.52 d (J = 2Hz, 1 H); 6.80 dd (J = 10.2 Hz, 1H); 7.18 with br (3H); 7.35-7.52 m (3H); 7.50-7.63 m (4H); 9.28 with br (1H).

6 - [[2- (3-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-2- (3-methylphenyl) -1-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. Mp 82-84 ° C.

Example 88

6 - [[2- (3-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by the reaction of 6-hydroxy-2- (3-methylphenyl) -1-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.22 d (J = 7.5 Hz, 6H); 1.38-1.56 m (2 H); 1.62-1.85 m (4H); 2.30 t (J = 7.5Hz, 2H); 2.30 s (3H); 3.93 t (J = 7.5Hz, 2H); 5.00 sp (J = 7.5Hz, 1H); 6.68 d (J = 2Hz, 1 H); 6.95 dd (J = 10.2 Hz, 1H); 7.13 with br (3H); 7.31 dd (J = 8.2Hz, 2H); 7.42-7.57 m (4H); 7.76 d (J = 10Hz, 1 H).

Example 89

6 - [[2- (3-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Obtained from 6 - [[2- (3-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.35-1.49 m (2H); 1.50-1.63 m (2H); 1.64-1.78 m (2H); 2.22 t (J = 7.5Hz, 2H); 2.24 s (3H); 3.92 t (J = 7.5Hz, 2H); 6.62 d (J = 2Hz, 1 H); 6.95 dd (J = 10.2 Hz, 1H); 7.18 with br (3H); 7.37-7.42 m (3H); 7.51-7.65 m (3H); 7.67 d (J = 10Hz, 1H); 11.90 with br (1H).

Example 90

6 - [[2- (3-methylphenyl) -l-phenyl-lH-benzimidazol-6-yl] oxy] hexan-l-ol

Obtained from 6 - [[2- (3-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 92-94 ° C.

Example 91

6 - [[2- (4-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 6-Methoxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole

It is prepared by reacting 4-methoxy-4'-phenyl-o-phenylenediamine with ethyl 4-methylbenzimidate hydrochloride (prepared according to: DeWolfe and Augustine, J. Org. Chem. 30, 699) according to general formula 4.

T. t. Mp 150-152 ° C.

b) 6-Hydroxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole

Prepared from 6-methoxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole according to general formula 7.

T. t. 257-264 ° C.

6 - [[2- (4-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6-hydroxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. Mp 99-102 ° C.

Example 92

6 - [[2- (4-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by the reaction of 6-hydroxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to General Regulation 8.

T. t. Mp 107-109 ° C.

Example 93

6 - [[2- (4-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Prepared from 6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.33-1.49 m (2H); 1.50-1.62 m (2H); 1.64-1.77 m (2H); 2.22 t (J = 7.5Hz, 2H); 2.30 s (3H); 3.901 (J = 7.5Hz, 2H); 6.62 d (J = 2Hz, 1 H); 6.94 dd (J = 10.2 Hz, 1H); 7.15 d (J = 8Hz, 2H); 7.36 d (J = 8Hz, 2H); 7.40 dd (J = 8.1.5 Hz, 2H); 7.52-7.62 m (3H); 7.68 d (J = 10Hz, 1 H).

Example 94

6 - [[2- (4-methylphenyl) -l-phenyl-lH-benzimidazol-6-yl] oxy] hexan-l-ol

Prepared from 6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to General Regulation 11.

T. t. Mp 150-152 ° C.

Example 95

6 - [[1-Phenyl-2- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 6-Methoxy-1-phenyl-2- (4-pyridyl) -1H-benzimidazole

To a solution of 0.4 g of 4-methoxy-N, ^2- phenyl-o-phenylenediamine in 8 ml of N, N-dimethylformamide is added 0.7 g of ethyl 2-ethoxy-1,2-dihydroquinoline-1-carboxylate and 0, 34 g of isonicotinic acid. The mixture was stirred at 100 ° C for 16 h. After cooling, it was diluted with water and extracted three times with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. After chromatography on silica gel, the amide obtained is refluxed with 5 ml of 6 N aqueous hydrochloric acid for 3 hours. After cooling, the mixture is stirred with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, the combined extracts are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl ₃ ): δ (ppm): 3.80 s (3H); 6.65 d (J = 2Hz, 1 H); 7.02 dd (J = 10.2 Hz, 1H); 7.32-7.38 m (2H); 7.42 dd (J = 8.1.5 Hz, 2H); 7.54-7.62 m (3H); 7.79 d (J = 10Hz, 1H); 8.53 d br (J = 6Hz, 2H).

b) 6-Hydroxy-1-phenyl-2- (4-pyridyl) -1H-benzimidazole

Prepared from 6-methoxy-1-phenyl-2- (4-pyridyl) -1H-benzimidazole according to general formula 7.

1 H-NMR (CD 3 OD): δ (ppm): 6.52 d (J = 2 Hz, 1H); 6.82 dd (J = 10.2 Hz, 1H); 7.28-7.33 m (2H); 7.39 dd (J = 8.1.5 Hz, 2H); 7.49-7.57 m (4H); 8.40 d br (J = 6Hz, 2H).

6 - [[1-Phenyl-2- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from 6-hydroxy-1-phenyl-2- (4-pyridyl) -1H-benzimidazole according to general formula 8. m.p. Mp 100-103 ° C.

Example 96

6 - [[1-Phenyl-2- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] -hexanoic acid

Obtained from 6 - [[1-phenyl-2- (4-pyridinyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 160-162 ° C.

Example 97

6 - [(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

a) 1,2-Diphenyl-6-hydroxy-5-nitro-1H-benzimidazole

b) 1,2-Diphenyl-6-hydroxy-7-nitro-1H-benzimidazole

c) 1,2-Diphenyl-6-hydroxy-5,7-dinitro-1H-benzimidazole

To a solution of 5 g of 1,2-diphenyl-6-hydroxy-1H-benzimidazole in 45 ml of acetic acid is added dropwise a solution of 1.67 g of potassium nitrite in 15 ml of water at 10-15 ° C. The mixture was stirred in an ice bath for 2 hours and at 20 ° C for 2 hours, concentrated in vacuo and the product purified by silica gel chromatography.

a) 1 H-NMR (CDCl ₃ ): δ (ppm): 6.83 s (1H); 7.25-7.44 m (5H); 7.52-7.60 m (5H); 8.66 s (1H); 10.78 s (1 H).

b) 1 H-NMR (d 6 -DMSO): δ (ppm): 7.05 d (J = 10 Hz, 1H); 7.30-7.53 m (10H); 7.82 d (J = 10Hz, 1H);

10.83 s (1 H).

c) 1 H-NMR (d 6 -DMSO): δ (ppm): 7.32-7.58 m (10H); 8.67 s (1H).

6 - [(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared by the reaction of 1,2-diphenyl-6-hydroxy-5-nitro-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to General Regulation 8.

T. t. Mp 123 ° C.

Example 98

6 - [(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester

It is prepared by reacting 1,2-diphenyl-6-hydroxy-5-nitro-benz-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

T. t. Mp 115-117 ° C.

Example 99

6 - [(1,2-Diphenyl-7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

It is prepared by the reaction of 1,2-diphenyl-6-hydroxy-7-nitro-ΙΗ-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. Mp 110-112 ° C.

Example 100

6 - [(1,2-Diphenyl-7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester

It is prepared by the reaction of 1,2-diphenyl-6-hydroxy-7-nitro-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

T. t. 88 ° C.

Example 101

6 - [(7-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

340 mg of 6 - [(1,2-diphenyl-7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester was hydrogenated in ethanol on Raney-nickel in an autoclave at 50 ° C at atmospheric pressure. After the hydrogen uptake is complete, the catalyst is filtered off and the filtrate is concentrated in vacuo.

T. t. Mp 113-115 ° C.

Example 102

6 - [(7-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester

Prepared from 6 - [(1,2-diphenyl-7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester analogously to Example 101.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.22 d (J = 7.5 Hz, 6H); 1.43-1.88 m (6H); 2.301 (J = 7.5Hz, 2H); 4.04 t (J = 7.5Hz, 2H); 5.00 sp (J = 7.5Hz, 1H); 6.97 d (J = 7.5Hz, 1H); 7.20-7.33 m (4H); 7.42-7.53 m (7H).

Example 103

6 - [(5,7-Dinitro-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

It is prepared by reacting 5,7-dinitro-1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

T. t. 88-91 DEG.

Example 104

6 - [(5,7-Dinitro-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester

It is prepared by reacting 5,7-dinitro-1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to general formula 8.

T. t. Mp 92-93 ° C.

Example 105

6 - [[5- (Acetylamino) -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 5-Fluoro-2,4-dinitrophenol

A solution of 0.41 g of 1,3-difluoro-4,6-dinitrobenzene in 8 ml of 0.5 N aqueous sodium hydroxide solution was refluxed for 2 hours. After cooling, the reaction mixture was diluted with water and extracted three times with diethyl ether. The aqueous phase is acidified with 1 N hydrochloric acid and then extracted with diethyl ether. The organic phase is dried over sodium sulphate and concentrated in vacuo.

1 H-NMR (CDCl ₃ ): δ (ppm): 7.10 d (J = 12 Hz, 1H); 9.03 d (J = 8Hz, 1H); 11.10 s (1H).

b) 2,4-Dmitro-5-hydroxydiphenylamine

To a suspension of 50 mg of 5-fluoro-2,4-dinitrophenol in 0.5 ml of ethanol is added 100 μΐ of aniline, the mixture is stirred for 30 minutes and then left to stand for 15 hours. The solid is filtered off with suction, washed with 1 N aqueous hydrochloric acid and dried under vacuum.

1 H-NMR (CDCl 3): δ (ppm): 6.58 s (1H); 7.31 d (J = 10Hz, 2H); 7.39 dd (J = 10, 10 Hz, 1H); 7.51 dd (J = 10, 10 Hz, 2H); 9.20 s (1H); 9.90 with br (1H); 10.97 with br (1H).

c) (2,4-Dinitro-5-phenylamino) phenylacetate

To a solution of 275 mg of 2,4-dinitro-5-hydroxydiphenylamine in 1 ml of pyridine was added 0.11 ml of acetic anhydride, the mixture was stirred in an ice bath for 30 minutes and then at 20 ° C for 1 hour. The reaction mixture was diluted with ethyl acetate and washed three times with glacial 1 N aqueous hydrochloric acid, once with saturated potassium bicarbonate solution and once with saturated sodium chloride solution. After drying over sodium sulfate, the solvent was evaporated in vacuo.

1 H-NMR (CDCl 3): δ (ppm): 2.34 s (3H); 6.80 s (1 H); 7.32 d (J = 10Hz, 2H); 7.40 dd (J = 10, 10 Hz, 1H); 7.52 dd (J = 10, 10 Hz, 2H); 9.21 s (1H); 9.95 with br (1H).

d) (1,2-Diphenyl-6-hydroxy-1H-benzimidazol-5-yl) acetamide

It is prepared from (2,4-dinitro-5-phenylamino) phenylacetate according to general formula 1 and subsequent reaction with trimethyl orthobenzoate according to general formula 3.

1 H-NMR (CDCl 3): δ (ppm): 2.26 s (3H); 6.88 s (1H); 7.22-7.36 m (5H); 7.42-7.53 m (5H); 7.61 s (1H);

8.43 with br (1H).

6 - [[5- (Acetylamino) -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of (1,2-diphenyl-6-hydroxy-1H-benzimidazol-5-yl) acetamide with 6-bromohexanoic acid methyl ester according to General Regulation 8.

T. t. Mp 128-130 ° C.

Example 106

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester

Prepared from 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester according to General Regulation 1.

1 H-NMR (CDCl 3): δ (ppm): 1.23 d (J = 7.5 Hz, 6H); 1.47-1.90 m (6H); 2.321 (J = 7.5Hz, 2H); 3.95 t (J = 7.5Hz, 2H); 5.02 sp (J = 7.5Hz, 1H); 6.60 s (1 H); 7.20 s (1H); 7.22-7.33 m (5H); 7.43-7.58 m (5H).

Example 107

6 - [[5 - [[(4-Bromophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 4-bromobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 173-175 ° C.

Example 108

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared from 6 - ((1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester according to General Regulation 1.

1 H-NMR (CDCl 3): δ (ppm): 1.48-1.88 m (6H); 2.361 (J = 7.5 Hz, 2H, = _CH2 CO); 3.67 s (3H); 3.94 t (J = 7.5Hz, 2H); 6.60 s (1 H); 7.21 s (1H); 7.22-7.35 m (5H); 7.43-7.59 m (5H).

Example 109

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 157-159 ° C.

Example 110

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reaction of 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 4-chlorobenzenesulphonic acid chloride according to General Regulation 13.

T. t. Mp 158-159 ° C.

Example 111

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared by reaction of 6 - [[5 - [[(4-chlorophenyl) -sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

T. t. Mp 201-203 ° C.

Example 112

6 - [[1,2-Diphenyl-5 - [[(3-methylphenyl) -sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reaction of 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 3-methylbenzenesulphonic acid chloride according to General Regulation 13.

T. t. Mp 149-151 ° C.

Example 113

6 - [[1,2-Diphenyl-5 - [[(4-methylphenyl) -sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reaction of 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 4-methylbenzenesulphonic acid chloride according to General Regulation 13.

T. t. 139-141 ° C.

Example 114

6 - [[1,2-Diphenyl-5 - [[(4-methoxyphenyl) -sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reaction of 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 4-methoxybenzenesulphonic acid chloride according to General Regulation 13.

1 H-NMR (CDCl 3): δ (ppm): 1.25 d (J = 7.5 Hz, 6H); 1.35-1.45 m (2H); 1.59-1.73 m (4H); 2.30 t (J = 7.5Hz, 2H); 3.72 t (J = 7.5Hz, 2H); 3.80 s (3H); 5.02 sp (J = 7.5Hz, 1H); 6.50 s (lH); 6.85 d (J = 10Hz, 2H); 6.99 s (1H); 7.25-7.35 m (5H); 7.45-7.52 m (5H); 7.74 d (J = 10Hz, 2H); 7.99 s (1 H).

Example 115

6 - [[1,2-Diphenyl-5 - [[[(4-trifluoromethyl) phenyl] sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reaction of 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 4-trifluoromethylbenzenesulphonic acid chloride according to General Regulation 13.

T. t. 170-171 [deg.] C.

Example 116

6 - [[5 - [[[4- (acetylamino) phenyl] sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Prepared by reaction of 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 4-acetylaminobenzenesulphonic acid chloride according to General Regulation 13.

T. t. Mp 100-102 ° C.

Example 117

6 - [[5 - [[Bis (3-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with 3-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 163-167 ° C.

Example 118

6 - [[1,2-Diphenyl-5 - [(propylsulfonyl) amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexane-isopropyl ester with propanesulfonic acid chloride according to general procedure 13.

T. t. Mp 126-128 ° C.

Example 119

6 - [[5 - [(Benzylsulfonyl) amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

It is prepared by reacting 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester with benzene methanesulfonic acid chloride according to General Regulation 13.

T. t. Mp 137-138 ° C.

Example 120

4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] methylbenzoic acid methyl ester

It is prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 4- (bromomethyl) benzoic acid methyl ester according to general formula 8.

T. t. Mp 180-184 ° C.

Example 121

4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] methylbenzoic acid

Prepared from 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] methylbenzoic acid methyl ester according to the procedure in General Regulation 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 5.12 s (2H); 6.76 d (J = 2Hz, 1 H); 7.04 dd (J = 10.2 Hz, 1H); 7.30-7.63 m (12H); 7.70 d (J = 10Hz, 1H); 7.89 d (J = 8Hz, 2H).

Example 122

4 - [[1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] methylbenzoic acid methyl ester

Prepared by reaction of 6-hydroxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole with 4- (bromomethyl) benzoic acid methyl ester according to the general formula 8.

T. t. 138-142 ° C.

Example 123

4 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] methylbenzoic acid methyl ester

Prepared by reacting 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole with 4- (bromomethyl) benzoic acid methyl ester according to General Regulation 8.

T. t. Mp 145-148 ° C.

Example 124

2- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] acetic acid tert-butyl ester

To a suspension of 0.2 g of [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethan-1-ol in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran is added 0.1 ml of tert-butyl ester bromoacetic acid, 13 mg tetrabutyl ammonium hydrogen sulfate and

1.45 ml of 32% sodium hydroxide solution and the mixture was stirred for 48 hours. An additional 0.1 ml of tert-butyl bromoacetate and 13 mg of tetrabutylammonium hydrogen sulfate are then added and the mixture is placed in an ultrasonic bath for 48 hours. Finally, it is diluted with water and extracted three times with toluene. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.43 s (9H); 3.91 t (J = 6Hz, 2H); 4.10 s (2H); 4.17 t (J = 6Hz, 2H); 6.75 d (J = 2Hz, 1 H); 7.00 dd (J = 10.2 Hz, 1H); 7.24-7.36 m (5H); 7.45-7.56 m (5H); 7.76 d (J = 10Hz, 1 H).

Example 125

2- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] acetic acid 2- [2 - [(1,2-Diphenyl-1H-benzimidazole) - tert -butyl ester 6-yl) oxy] ethoxy] acetic acid was dissolved in 0.5 mL trifluoroacetic acid and allowed to stir for 48 hours. It is then diluted with water and extracted three times with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

T. t. Mp 134-136 ° C.

Example 126

2- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] ethoxy] acetic acid methyl ester mg of 2- [2 - [(1,2-Diphenyl-1H-benzimidazole-6-) yl) oxy] -ethoxy] acetic acid is dissolved in 0.4 ml of N, N-dimethylformamide and 29 mg of cesium carbonate and 50 μΐ of methyl iodide are added. The mixture was stirred for 20 hours, concentrated in vacuo and chromatographed on silica gel.

1 H-NMR (CDCl 3): δ (ppm): 3.73 s (3H); 3.93 t (J = 6Hz, 2H); 4.18 t (J = 6Hz, 2H); 4.25 s (2H); 6.73 d (J = 2Hz, 1 H); 7.00 dd (J = 10.2 Hz, 1H); 7.25-7.42 m (5H); 7.46-7.58 m (5H); 7.77 d (J = 10Hz, 1Η).

Example 127

3- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] propanoic acid tert-butyl ester

To a suspension of 0.2 g of [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethan-1-ol in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran is added 60 μΐ of t-butyl acrylate. 13 mg tetrabutyl ammonium hydrogen sulfate a

1.45 ml of 32% sodium hydroxide solution and the mixture was stirred for 48 hours. An additional 60 μΐ of acrylic acid tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfate are then added and the mixture is placed in an ultrasonic bath for 48 hours. Finally, it is diluted with water and extracted three times with toluene. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

Ή-NMR (CDCl 3): δ (ppm): 1.45 s (9H); 2.52 t (J = 8Hz, 2H); 3.73-3.84 m (4H); 4.101 (J = 6Hz, 2H); 6.72 d (J = 2Hz, 1 H); 6.99 dd (J = 10.2 Hz, 1H); 7.22-7.38 m (5H); 7.45-7.57 m (5H); 7.75 d (J = 10 Hz, 1Η).

Example 128

3- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] propanoic acid 3- [2 - [(1,2-Diphenyl-1H-benzimidazole-6) -butyl ester -yl) oxy] ethoxy] propanoic acid was dissolved in 0.5 ml of trifluoroacetic acid and stirred for 15 hours. It is then diluted with water and extracted three times with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (d 6 -DMSO): δ (ppm): 2.261 (J = 8 Hz, 2H); 3.60-3.70 m (4H); 3.98-4.06 m (2H); 6.65 d (J = 2Hz, 1 H); 6.94 dd (J = 10.2 Hz, 1H); 7.30-7.62 m (10H); 7.68 d (J = 10Hz, 1 H).

Example 129

3- [2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] propanoic acid methyl ester mg of 3- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) (1) oxy] -ethoxy] propane are dissolved in 0.4 ml of N, N-dimethylformamide and 28 mg of cesium carbonate and 50 μitanu of methyl iodide are added and the mixture is stirred for 30 hours. Water was then added and the mixture was extracted three times with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

T. t. 91-93 ° C.

Example 130

3- [3 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] propoxy] propanoic acid tert-butyl ester

0.2 g of 3 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] propan-1-ol was suspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. To this suspension was added 60 μΐ of tert-butyl acrylate, 13 mg of tetrabutylammonium hydrogen sulfate and 1.47 ml of 32% sodium hydroxide solution, and the mixture was stirred for 48 hours. An additional 60 µl of tert-butyl acrylate and 13 mg of tetrabutylammonium hydrogen sulfate are then added and the mixture is placed in an ultrasonic bath for 48 hours. Finally, the reaction mixture is diluted with water and extracted three times with toluene. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

T. t. Mp 95-98 ° C.

Example 131

(E / Z) -5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pent-4-enoic acid methyl ester

a) 1,2-Diphenyl-6-methyl-1H-benzimidazole

5.1 g of 5-methyl-2-nitrodiphenylamine are hydrogenated in 55 ml of ethanol according to general formula 1 and the crude product is reacted with trimethyl orthobenzoate according to general formula 3.

T. t. Mp 134-136 ° C.

b) 1,2-Diphenyl-1H-benzimidazole-6-carbaldehyde

To a suspension of 1 g of 1,2-diphenyl-6-methyl-1H-benzimidazole in 31 ml of 40% sulfuric acid is added 13.5 g of cerium ammonium nitrate. The mixture was stirred at 80 ° C for 2.5 hours, cooled to 20 ° C, and added cautiously to saturated aqueous sodium bicarbonate while stirring. The mixture is extracted three times with ethyl acetate, the combined extracts are washed with saturated sodium chloride solution, dried over sodium sulfate and the solvent is evaporated to dryness in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ (ppm): 7.30-7.42 m (5H); 7.50-7.66 m (5H); 7.81 d (J = 2Hz, 1 H); 7.89 dd (J = 8.2 Hz, 1H); 8.00 d (J = 8Hz, 1 H); 10.05 s (1H).

(E / Z) -5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pent-4-enoic acid methyl ester

Prepare by reaction of 1,2-diphenyl-1H-benzimidazole-6-carbaldehyde with 3-carboxypropyltriphenylphosphonium bromide according to the general formula 12.

1 H-NMR (CDCl 3): δ (ppm): 2.40-2.71 m (4H); 3.68 s (3H); 3.66 s (3H); 5.56-5.64 m (lH); 6.12-6.22 m (1H); 6.50 d (J = 18 Hz, 1H); 6.58 d br (J = 12Hz, 1H); 7.12 with br (1H); 7.15 with br (1H); 7.25-7.40 m (6H); 7.45-7.62 m (5H); 7.80 d (J = 8Hz, 1H); 7.83 d (J = 8Hz, 1H).

Example 132

(E) -5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pent-4-enoic acid

Prepared from (E / Z) -5- (1,2-diphenyl-1H-benzimidazol-6-yl) pent-4-enoic acid methyl ester according to the general formula 9.

1 H-NMR (CD ₃ OD): δ (ppm): 2.26-2.43 m (4H); 6.10-6.21 m (1H); 6.45 d (J = 18Hz, 1H); 7.08 s (1H); 7.22-7.52 m (11H); 7.59 d (J = 8Hz, 1H).

Example 133

5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pentanoic acid methyl ester

Prepared from (E / Z) -5- (1,2-diphenyl-1H-benzimidazol-6-yl) pent-4-enoic acid methyl ester according to General Regulation 1.

1 H-NMR (CDCl 3): δ (ppm): 1.63-1.72 m (4H); 2.30-2.39 m (2H); 2.68-2.77 m (2H); 3.65 s (3H); 7.04 with br (1H); 7.17 dd (J = 8.2 Hz, 1H); 7.25-7.38 m (5H); 7.45-7.60 m (5H); 7.79 d (J = 8Hz, 1 H).

Example 134

5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pentanoic acid

Prepared from methyl 5- (1,2-diphenyl-1H-benzimidazol-6-yl) pentanoic acid methyl ester according to the general formula 9.

Mp 1.192-193 ° C.

Example 135

(E / Z) -6- (1,2-Diphenyl-1H-benzimidazol-6-yl) hex-5-enoic acid methyl ester

Obtained from 1,2-diphenyl-1H-benzimidazole-6-carbaldehyde and 4-carboxybutyltriphenylphosphonium bromide according to the general formula 12.

1 H-NMR (CDCl 3): δ (ppm): 1.72-1.88 m (2H); 2.20-2.42 m (4H); 3.65 s (3H, _CH3); 3.67 s (3H, _CH3); 5.57-5.68 m (lH); 6.10-6.20 m (lH); 6.48 d (J = 18Hz, 1H); 6.56 d br (J = 12Hz, 1H); 7.12 with br (1H); 7.16 with br (1H); 7.25-7.38 m (6H); 7.45-7.60 m (5H); 7.80 d (J = 8Hz, 1H); 7.84 d (J = 8Hz, 1 H).

Example 136

(E / Z) -6- (1,2-Diphenyl-1H-benzimidazol-6-yl) hex-5-enoic acid

Prepared from (E / Z) -6- (1,2-diphenyl-1H-benzimidazol-6-yl) hex-5-enoic acid methyl ester according to the general formula 9.

1 H-NMR (CDCl 3): δ (ppm): 1.74-1.89 m (2H); 2.22-2.43 m (4H); 5.58-5.68 m (lH); 6.10-6.22 m (1H); 6.47 d (J = 18Hz, 1H); 6.55 d br (J = 12Hz, 1H); 7.11 s (1H); 7.14 s (1H); 7.25-7.40 m (6H); 7.48-7.59 m (5H); 7.80 d (J = 8Hz, 1H); 7.85 d (J = 8Hz, 1 H).

Example 137

6- (1,2-Diphenyl-1H-benzimidazol-6-yl) hexanoic acid methyl ester

Prepared from (E / Z) -6- (1,2-diphenyl-1H-benzimidazol-6-yl) hex-5-enoic acid methyl ester according to General Regulation 1.

1 H-NMR (CDCl 3): δ (ppm): 1.32-1.43 m (2H); 1.62-1.74 m (4H); 2.311 (J = 7.5Hz, 2H); 2.72 t (J = 7.5Hz, 2H); 3.56 s (3H); 7.02 with br (1H); 7.18 dd (J = 8.2 Hz, 1H); 7.27-7.38 m (5H); 7.45-7.60 m (5H); 7.80 d (J = 8Hz, 1H).

Example 138

6- (1,2-Diphenyl-1H-benzimidazol-6-yl) hexanoic acid

Prepared from 6- (1,2-diphenyl-1H-benzimidazol-6-yl) -hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (CDCl 3): δ (ppm): 1.30-1.45 m (2H); 1.54-1.74 m (4 H); 2.32 t (J = 7.5Hz, 2H); 2.70 t (J = 7.5Hz, 2H); 7.02 with br (1H); 7.20 dd (J = 8.2 Hz, 1H); 7.25-7.38 m (5H); 7.42-7.60 m (5H); 7.81 d (J = 8Hz, 1 H).

Example 139

(E / Z) -7- (1,2-Diphenyl-1H-benzimidazol-6-yl) -hept-6-enoic acid methyl ester

Prepared by the reaction of 1,2-diphenyl-1H-benzimidazole-6-carbaldehyde with 5-carboxybutyltriphenylphosphonium bromide according to the general formula 12.

1 H-NMR (CDCl 3): δ (ppm): 1.43-1.55 m (2H); 1.58-1.72 m (2H); 2.18-2.38 m (4H); 3.65 s (3H, _CH3);

3.66 s (3H, CH3); 5.58-5.68 m (lH); 6.12-6.22 m (1H); 6.45 d (J = 18Hz, 1H); 6.54 d br (J = 12Hz, 1H); 7.12 with br (1H); 7.14 with br (1H); 7.26-7.40 m (6H); 7.48-7.60 m (5H); 7.80 d (J = 8Hz, 1H); 7.83 d (J = 8Hz, 1H).

Example 140

(E / Z) -7- (1,2-Diphenyl-1H-benzimidazol-6-yl) hept-6-enoic acid

Prepared from (E / Z) -7- (1,2-diphenyl-1H-benzimidazol-6-yl) hept-6-enoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.40-1.60 m (4H); 2.14-2.28 m (4H); 6.18-6.30 m (1H); 6.50 d (J = 18 Hz, 1H); 7.07 with br (1H); 7.12 with br (1H); 7.32-7.64 m (11H); 7.70 d (J = 8Hz, 1H); 7.78 d (J = 8Hz, 1H); 12.00 with br (1H).

Example 141

7- (1,2-Diphenyl-1H-benzimidazol-6-yl) heptanoic acid methyl ester

Prepared from (E / Z) -7- (1,2-diphenyl-1H-benzimidazol-6-yl) hept-6-enoic acid methyl ester according to General Regulation 1.

1 H-NMR (CDCl 3): δ (ppm): 1.30-1.42 m (4H); 1.55-1.70 m (4H); 2.301 (J = 7.5Hz, 2H); 2.68 t (J = 7.5Hz, 2H); 3.56 s (3H); 7.02 with br (1H); 7.18 dd (J = 8.2 Hz, 1H); 7.28-7.35 m (5H); 7.45-7.58 m (5H); 7.79 d (J = 8Hz, 1 H).

Example 142

7- (1,2-Diphenyl-1H-benzimidazol-6-yl) heptanoic acid

Prepared from 7- (1,2-diphenyl-1H-benzimidazol-6-yl) -heptanoic acid methyl ester according to the general formula 9.

T. t. Mp 99-103 ° C.

Example 143

N - (1,2-Diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 144 N- (Phenylsulfonyl) -N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

a) 5-Amino-1,2-diphenyl-1H-benzimidazole

It is prepared by reacting 2,4-diaminodiphenylamine with trimethyl orthobenzoate according to general formula 3.

1 H-NMR (CDCl 3): δ (ppm): 6.70 dd (J = 7.5, 2 Hz, 1H); 7.06 d (J = 7.5Hz, 1H); 7.18 d (J = 2Hz, 1 H); 7.28-7.60 m (10H).

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with benzenesulfonyl chloride according to general formula 13.

143: 1.1. Mp 196-205 ° C.

144: 1 H-NMR (CDCl 3): δ (ppm): 6.94 dd (J = 7.5, 2 Hz, 1H); 7.20 d (J = 2Hz, 1H); 7.26-8.04 m (21H).

Example 145

-Chloro-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 146 N - [(3-Chlorophenyl) sulfonyl] -N- (1,2-diphenyl-1H-benzimidazol-5-yl) - (3-chlorobenzene) sulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with 3-chlorobenzenesulfonyl chloride according to general formula 13.

145: 1.1. Mp 160-162 ° C.

144: 1 H-NMR (CDCl 3): δ (ppm): 6.93 dd (J = 7.5, 2 Hz, 1H); 7.25 d (J = 2Hz, 1 H); 7.28-7.57 m (13H);

7.66 d (br, 2H); 7.90 d br (2H); 8.00 d br (2H).

Example 147

4-Chloro- / V- (l, 2-diphenyl-lH-benzoimidazol-5-yl) -benzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with 4-chlorobenzenesulfonyl chloride according to general formula 13.

1 H-NMR (CDCl 3): δ (ppm): 6.86 s br (1H); 7.11 d (J = 7.5, 2 Hz, 1H); 7.17 d (J = 2Hz, 1 H); 7.25-7.55 m (12H); 7.70 d (J = 10Hz, 2H).

Example 148

4-Bromo-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 149

A - [(4-bromo-phenylsulfonyl) -7V- (l, 2-diphenyl-lH-benzoimidazol-5-yl)] - 4-bromobenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with 4-bromobenzenesulfonyl chloride according to general formula 13.

148: 1.1. Mp 135-139 ° C.

149: 1 H-NMR (CDCl ₃ ): δ (ppm): 6.90 dd (J = 7.5, 2 Hz, 1H); 7.23 d (J = 2Hz, 1 H); 7.28-7.43 m (11H);

7.72 d (J = 10Hz, 2H); 7.86 d (J = 10Hz, 2H).

Example 150

4- (Trifluoromethyl) -N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 151

N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -N- [(3-trifluoromethyl) phenylsulfonyl] - (3-trifluoromethyl) benzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with (3-trifluoromethyl) benzenesulfonyl chloride according to general formula 13.

150: 1.1. Mp 116-121 ° C.

151: 1.1. 238-224 ° C.

Example 152

3-Methyl-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 153 N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -N- (3-methylphenylsulfonyl) -3-methylbenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole was reacted with 3-methylbenzenesulfonyl chloride according to the general formula 13.

152: 1.1. Mp 192-195 ° C.

153: 1.1. Mp 173-176 ° C.

Example 154

4-Methyl-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 155 N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -N- (4-methylphenylsulfonyl) -4-methylbenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with 4-methylbenzenesulfonyl chloride according to general formula 13.

154: 1 H-NMR (CDCl ₃ ): δ (ppm): 2.38 s (3H); 6.77 with br (1H); 7.14-7.55 m (14H); 7.66 d (J = 10Hz, 2H).

155: 1.1. Mp 234-236 ° C.

Example 156

4-Methoxy-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 157

N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -N- (4-methoxyphenylsulfonyl) -4-methoxybenzenesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with 4-methoxybenzenesulfonyl chloride according to the general formula 13.

156: 1 H-NMR (CDCl ₃ ): δ (ppm): 3.82 s (3H); 6.78 with br (1H, H-4); 6.88 d (J = 7.5Hz, 1H); 7.14 d (J = 1.5 Hz, 1H); 7.28-7.55 m (12H); 7.72 d (J = 8Hz, 2H).

157: 1 H-NMR (CDCl ₃ ): δ (ppm): 3.90 s (6H); 6.93 dd (J = 7.5, 2 Hz, 1H); 7.00 d (J = 10Hz, 4H); 7.06 d (J = 2Hz, 1 H); 7.30-7.58 m (11H); 7.93 d (J = 10Hz, 4H).

Example 158

7V- (l, 2-diphenyl-lH-benzoimidazol-5-yl) propanesulfonamide

Example 159

N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -N- (propylsulfonyl) propane sulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with propanesulfonyl chloride according to general formula 13.

158: 1 H-NMR (CDCl 3 / d 6 -DMSO): δ (ppm): 0.80 t (J = 7.5 Hz, 3H); 1.65 m (2H); 2.82 m (2H); 6.95 d (J = 7.5Hz, 1H); 7.08 dd (J = 7.5, 2 Hz, 1H); 7.10-7.40 m (10H); 7.61 d (J = 2Hz, 1 H); 9.05 with br (1H, NH).

159: 1 H-NMR (CDCl ₃ ): δ (ppm): 1.08 t (J = 7.5 Hz, 3H); 1.12 t (J = 7.5Hz, 3H); 2.00 m (4H); 3.60 m (4H);

7.25-7.63 m (13H).

Example 160 N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -benzenemethanesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is reacted with benzenemethanesulfonyl chloride according to general formula 13.

T. t. Mp 185-188 ° C.

Example 161

6 - [[1,2-Diphenyl-1H-benzimidazol-5-yl] amino] -hexanoic acid methyl ester

Example 162

6- [N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -N - [(5-methoxycarbonyl) pentyl] amino] hexanoic acid methyl ester

To a solution of 285 mg of 5-amino-1,2-diphenyl-1H-benzimidazole in 5 ml of methanol is added 207 mg of 6-bromohexanoic acid methyl ester, 138 mg of potassium carbonate and 150 mg of sodium iodide, and the mixture is allowed to stir at 20 C. Water is then added, extracted three times with ethyl acetate, the combined organic phases are dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on silica gel.

161: 1.1. Mp 109-113 ° C.

162: 1 H-NMR (CDCl ₃ ): δ (ppm): 1.30-1.43 m (4H); 1.53-1.73 m (8H); 2.32 t (J = 7.5Hz, 4H); 3.30 t (J = 7.5Hz, 4H); 3.68 s (6H); 6.75 dd (J = 10.2 Hz, 1H); 7.10 d (J = 10Hz, 1H); 7.14 d (J = 2Hz, 1 H); 7.23-7.35 m (5H); 7.42-7.58 m (5H).

Example 163

6 - [[1,2-Diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid

Prepared from methyl 6 - [[1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.35-1.50 m (2H); 1.50-1.68 m (4H); 2.23 t (J = 7.5Hz, 2H); 3.05 t (J = 7.5Hz, 2H); 6.67 dd (J = 10.2 Hz, 1H); 6.80 d (J = 2Hz, 1 H); 6.92 d (J = 10Hz, 1H); 7.30-7.40 m (4H); 7.45-7.62 m (6H).

Example 164

6 - [[2-Phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) (5-Hydroxy-2-nitrophenyl) [4- (phenylmethoxy) phenyl] amine

A mixture of 1 g of 3-fluoro-4-nitrophenol and 3.8 g of 4-benzyloxyaniline is stirred for 6.5 hours at 150 ° C. The reaction mixture was then diluted with dichloromethane. After extraction twice with 1 N aqueous hydrochloric acid and washing with water, it is extracted twice with 2 N aqueous sodium hydroxide solution. Ethyl acetate and 1 N aqueous hydrochloric acid were added to the basic aqueous phase. After phase separation, the organic phase is washed several times with 1 N aqueous hydrochloric acid and saturated sodium chloride solution. After drying over sodium sulfate and evaporation of the solvent in vacuo, the residue is chromatographed on silica gel.

1 H-NMR (d 6 -DMSO): δ (ppm): 5.14 s (2H); 6.23 m (2H); 7.10 d (J = 8Hz, 2H); 7.26 d (J = 8Hz, 2H); 7.32-7.52 m (5H); 8.03 d (J = 8Hz, 1H); 9.52 s (1H); 10.71 s (1 H).

b) 6 - [[4-Nitro-3 - [[4- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid methyl ester

Prepared by reaction of (5-hydroxy-2-nitrophenyl) [4- (phenylmethoxy) phenyl] amine with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.37-1.50 m (2H); 1.59-1.80 m (4H); 2.33 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.83 t (J = 7.5Hz, 2H); 5.12 s (2H); 6.24-6.33 m (2H); 7.04 d (J = 8Hz, 2H); 7.21 d (J = 8Hz, 2H); 7.32-7.50 m (5H); 8.17 d (J = 8Hz, 1H); 9.66 s (1 H).

6 - [[2-Phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reduction of 6 - [[4-nitro-3 - [[4- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid methyl ester according to General 2 and subsequent cyclization with trimethyl orthobenzoate according to General 3.

1 H-NMR (CDCl 3): δ (ppm): 1.43-1.58 m (2H); 1.65-1.86 m (4H); 2.35 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.94 t (J = 7.5Hz, 2H); 5.14 s (2H); 6.64 d (J = 2Hz, 1 H); 6.95 dd (J = 8.2 Hz, 1H); 7.11 d (J = 8Hz, 2H); 7.18-7.61 m (12H); 7.74 d (J = 8Hz, 1H).

Example 165

6 - [[2-Phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[2-phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.36-1.62 m (4H); 1.65-1.78 m (2H); 2.22 t (J = 7.5Hz, 2H); 3.92 t (J = 7.5Hz, 2H); 5.18 s (2H); 6.59 d (J = 2Hz, 1 H); 6.92 dd (J = 8.2 Hz, 1H); 7.20 d (J = 8Hz, 2H); 7.30-7.54 m (12H);

7.66 d (J = 8Hz, 1H).

Example 166

6 - [[1- (4-Hydroxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 - [[2-phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] -oxanoic acid according to General Regulation 1.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.37-1.79 m (6H); 2.22 t (J = 7.5Hz, 2H); 3.92 t (J = 7.5Hz, 2H); 6.60 d (J = 2Hz, 1 H); 6.91 dd (J = 8.2 Hz, 1H); 6.94 d (J = 8.2 Hz, 2H); 7.20 d (J = 8Hz, 2H); 7.36 m (3 H); 7.52 m (2 H); 7.63 d (J = 8Hz, 1H).

Example 167

6 - [[2-Phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) (5-Hydroxy-2-nitrophenyl) [3- (phenylmethoxy) phenyl] amine

A mixture of 1 g of 3-fluoro-4-nitrophenol and 3.81 g of 3-benzyloxyaniline was stirred at 150 ° C for 22 hours. The mixture was diluted with a small amount of dichloromethane and chromatographed directly on silica gel.

1 H-NMR (CDCl 3): δ (ppm): 5.10 s (2H); 5.82 with br (1H); 6.27 dd (J = 8.2 Hz, 1H); 6.48 d (J = 2Hz, 1 H);

6.86 m (3 H); 7.28-7.48 m (5H); 8.15 d (J = 8Hz, 1H); 9.52 with br (1H); 10.71 s (1 H).

b) 6 - [[4-Nitro-3 - [[3- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid methyl ester

Prepared by reaction of (5-hydroxy-2-nitrophenyl) [3- (phenylmethoxy) phenyl] amine with methyl 6-bromohexanoate according to General Regulation 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.40-1.53 m (2H); 1.61-1.82 m (4H); 2.341 (J = 7.5Hz, 2H); 3.67 s (3H); 3.88 t (J = 7.5Hz, 2H); 5.10 s (2H); 6.33 dd (J = 8.2 Hz, 1H); 6.58 d (J = 2Hz, 1 H); 6.83-6.96 m (3H); 7.28-7.49 m (5H); 8.17 d (J = 8Hz, 1H); 9.74 with br.

6 - [[2-Phenyl-1- [3- (phenylmethoxy) -phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reduction of 6 - [[4-nitro-3 - [[3- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid methyl ester according to General 2 and subsequent cyclization with trimethyl orthobenzoate according to General 3.

1 H-NMR (CDCl 3): δ (ppm): 1.45-1.60 m (2H); 1.66-1.88 m (4H); 2.35 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.93 t (J = 7.5Hz, 2H); 5.02 s (2H); 6.69 d (J = 2Hz, 1 H); 6.90 m (2H); 6.97 dd (J = 8.2 Hz, 1H); 7.11 ddd (J = 8.2,2Hz, 1H); 7.28-7.46 m (9H); 7.78 d (J = 8Hz, 1 H).

Example 168

6 - [[2-Phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid

Obtained from 6 - [[2-phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to protocol 9.

1 H-NMR (CDCl 3): δ (ppm): 1.49-1.62 m (2H); 1.67-1.88 m (4H); 2.39 t (J = 7.5Hz, 2H); 3.93 t (J = 7.5Hz, 2H); 5.03 s (2H); 6.68 d (J = 2Hz, 1 H); 6.91 m (3 H); 6.98 dd (J = 8.2 Hz, 1H); 7.12 ddd (J = 8.2,2Hz, 1H); 7.29-7.47 m (8H); 7.57 d (J = 8Hz, 1H); 7.81 d (J = 8Hz, 1 H).

Example 169

6 - [[1- (3-Hydroxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared from 6 [[2-phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to General Regulation 1.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.39-1.80 m (6H); 2.23 t (J = 7.5Hz, 2H); 3.94 t (J = 7.5Hz, 2H); 6.57 d (J = 2Hz, 1 H); 6.74 dd (J = 2.2 Hz, 1H); 6.84 dd (J = 8.2 Hz, 1H); 6.94 m (2 H); 7.38 m (4H); 7.53 m (2 H); 7.66 d (J = 8Hz, 1H).

Example 170

6 - [[1- (3-Hydroxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared from 6 - [[2-phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to General Regulation 1.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.38-1.80 m (6H); 2.32 t (J = 7.5Hz, 2H); 3.59 s (3H); 3.94 t (J = 7.5Hz, 2H); 6.66 d (J = 2Hz, 1 H); 6.74 dd (J = 2.2 Hz, 1H); 6.83 dd (J = 8.2 Hz, 1H); 6.93 dd (J = 8.2 Hz, 2H); 7.38 m (4H); 7.54 m (2 H); 7.67 d (J = 8Hz, 1H).

Example 171

6 - [[1- (3-Nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid ethyl ester

It is prepared by the reaction of 6-hydroxy-1- (3-nitrophenyl) -2-phenylbenzimidazole (DE 4330959) with 6-bromohexanoic acid ethyl ester according to general regulation 8.

T. t. Mp 104-106 ° C.

Example 172

6 - [[4-Bromo-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 4-Bromo-6-methoxy-2-phenyl-1H-benzimidazole

To 36.6 g of 4-amino-3-bromo-5-nitroanisole (J. Chem. Soc. 1966, 1769) in 750 ml of ethanol is added 19.8 g of iron powder and 126 ml of acetic acid. The mixture was stirred at 55 ° C for 2.5 hours, then 350 mL of dichloromethane was added and basified with 2 N sodium hydroxide. After filtration through celite, the filtrate was washed with water and saturated sodium chloride solution and the solvent was evaporated. The crude phenylenediamine thus obtained is reacted with trimethyl orthobenzoate according to general formula 3.

T. t. Mp 203-205 ° C.

b) 4-Bromo-6-methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

A mixture of 2.5 g of 4-bromo-6-methoxy-2-phenyl-1H-benzimidazole, 2.24 g of 4- (methylbenzene) boronic acid, 1.5 g of copper (II) acetate and about 3 g of molecular sieve in 35 ml of pyridine is stirred at 100 ° C for 7 hours. After addition of dichloromethane and celite, the mixture was concentrated and chromatographed on silica gel with hexane-ethyl acetate.

T. t. Mp 209-210 ° C.

c) 4-Bromo-6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

A mixture of 1.2 g of 4-bromo-6-methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole, 6 ml of acetic acid and 6 ml of aqueous hydrobromic acid (62%) is heated to boiling. for 5.5 hours. Water is then added and the precipitate formed is filtered off with suction and partitioned between ethyl acetate and 2N sodium hydroxide. After washing the organic phase with water, the solvent is evaporated.

T. t. Mp 136-137 ° C.

6 - [[4-Bromo-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 4-bromo-6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8.

Mp 1.136 ° C.

Example 173

6 - [[4-Acetyl-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

A mixture of 0.5 g of 4-bromo-6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole, 0.37 ml of (.alpha.-ethoxyvinyl) tributyltin and 140 mg of dichlorobis (triphenylphosphine) palladium in 10 ml. of toluene was stirred at 100 ° C for 18 hours. After cooling, the mixture was stirred with 2 N aqueous hydrochloric acid for 0.25 hours. After phase separation, the organic phase is washed with water and concentrated. The residue is chromatographed on silica gel with hexane-ethyl acetate.

T. t. Mp 114-115 ° C.

Example 174

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

a) 5-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

16.8 g of 5-methoxy-2-phenyl-1H-benzimidazole (Bull. Sci. Fac. Chim. Ind. Bologna 11, 42 (1953)) is reacted with 20.4 g of 4- (methylbenzene) boronic acid according to of the General Regulation 14.

1 H-NMR (CDCl 3): δ (ppm): 2.45 s (3H); 3.91 s (3H); 6.90 dd (J = 8.2 Hz, 1H); 7.12 d (J = 8Hz, 1H); 7.18 d (J = 8Hz, 2H); 7.25-7.38 m (6H); 7.57 m (2 H).

In addition, 6-methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole is also obtained.

b) 5-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

Prepared from 5-methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole according to general formula 6.

T. t. 270 ° C.

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of 5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.48-1.92 m (6H); 2.38 t (J = 7.5Hz, 2H); 2.46 s (3H); 3.69 s (3H); 4.06 t (J = 7.5Hz, 2H); 6.89 dd (J = 8.2 Hz, 1H); 7.11 d (J = 8Hz, 1H); 7.18 d (J = 8Hz, 2H); 7.24-7.37 m (6H); 7.57 m (2 H).

Example 175

6 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid

Obtained from 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

1 H-NMR (d 6 -DMSO): δ (ppm): 1.41-1.67 m (4H); 1.70-1.83 m (2H); 2.26 t (J = 7.5Hz, 2H); 2.43 s (3H);

4.05 t (J = 7.5Hz, 2H); 6.90 dd (J = 8.2 Hz, 1H); 7.04 d (J = 8Hz, 1H); 7.23-7.40 m (8H); 7.52 m (2 H); 11.92 with br (1H).

Example 176

6 - [[2-Phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

(a) 6 - [[2-Phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 4,84 g of 2-phenyl-5-hydroxy-1H-benzimidazole (Izv. Akad. USSR, USSR Ser. Chim. 8, 1888 (1990)) with methyl 6-bromohexanoate according to general formula 8.

1 H-NMR (CDCl 3): δ (ppm): 1.43-1.58 m (2H); 1.64-1.87 m (4H); 2.37 t (J = 7.5Hz, 2H); 3.69 s (3H); 3.94 t (J = 7.5Hz, 2H); 6.87 dd (J = 8.2Hz, 1H); 7.02 s br; 7.40-7.57 m (4H); 8.05 m (2H).

6 - [[2-Phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid with 4- (thiomethylbenzene) boronic acid according to the general formula 14.

1 H-NMR (CDCl 3): δ (ppm): 1.48-1.61 m (2H); 1.66-1.92 m (4H); 2.361 (J = 7.5Hz, 2H); 2.54 s (3H); 3.68 s (3H); 4.05 t (J = 7.5Hz, 2H); 6.90 dd (J = 8.2 Hz, 1H); 7.11 d (J = 8Hz, 1H); 7.22 d (J = 8Hz, 2H); 7.27-7.49 m (6H); 7.57 m (2 H).

Example 177

6 - [[2-Phenyl-1 - [(4-thiomethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[2-phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid with 4- (thiomethylbenzene) boronic acid according to the general formula 14.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.45-1.57 m (2H); 1.62-1.86 m (4H); 2.441 (J = 7.5Hz, 2H); 2.56 s (3H); 3.66 s (3H); 3.93 t (J = 7.5Hz, 2H); 6.66 d (J = 2Hz, 1 H); 6.96 dd (J = 8.2 Hz, 1H); 7.18-7.39 m (7H); 7.54 m (2 H);

7.73 d (J = 8Hz, 1 H).

Example 178

6 - [[2-Phenyl-1- (3-thienyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of 6 - [[2-phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester with thiophene-3-boronic acid according to the general formula 14.

1 H-NMR (CDCl 3): δ (ppm): 1.48-1.62 m (2H); 1.66-1.92 m (4H); 2.47 t (J = 7.5Hz, 2H); 3.68 s (3H); 4.04 t (J = 7.5Hz, 2H); 6.93 dd (J = 8.2 Hz, 1H); 6.98 dd (J = 5.1 Hz, 1H); 7.18 d (J = 8Hz, 1H); 7.28 dd (J = 3.1 Hz, 1H); 7.30-7.40 m (4H); 7.46 dd (J = 5.3 Hz, 1H); 7.60 m (2 H).

Example 179

6 - [[2-Phenyl-1- (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of 6 - [[2-phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester with thiophene-3-boronic acid according to the general formula 14.

1 H-NMR (CDCl 3): δ (ppm): 1.45-1.58 m (2H); 1.64-1.87 m (4H); 2.35 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.97 t (J = 7.5Hz, 2H); 6.74 d (J = 2Hz, 1 H); 6.95 dd (J = 8.2 Hz, 1H); 7.01 dd (J = 5.1 Hz, 1H); 7.29 dd (J = 3.1 Hz, 1H); 7.30-7.38 m (4H); 7.47 dd (J = 5.3 Hz, 1H); 7.58 m (2 H); 7.73 d (J = 8Hz, 1 H).

Example 180

4- [3 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] butanoic acid methyl ester

a) 6- (3-Methoxyphenoxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

Prepared from 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole and 3-methoxybenzeneboronic acid according to General Regulation 14.

T. t. Mp 120-122 ° C.

b) 3 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol

Prepared from 6- (3-methoxyphenoxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazole according to general formula 6 with addition of 10 mol% hexadecyltributylphosphonium bromide.

T. t. Mp 252-253 ° C.

4- [3 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] butanoic acid methyl ester

Prepared by reaction of 3 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol with 4-bromobutyric acid methyl ester according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 2.00-2.13 m (2H); 2.43 s (3H); 2.50 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.93 t (J = 7.5Hz, 2H); 6.44-6.62 m (3H); 6.95 d (J = 2Hz, 1 H); 7.06 dd (J = 8.2 Hz, 1H); 7.12-7.22 m (3H); 7.25-7.39 m (5H); 7.59 m (2 H); 7.87 d (J = 8Hz, 1H).

Example 181

4- [4 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] butanoic acid methyl ester

a) 6- (4-Methoxyphenoxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazole

Obtained from 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole and 4-methoxybenzeneboronic acid according to the general formula 14.

1 H-NMR (CDCl 3): δ (ppm): 2.44 s (3H); 3.79 s (3H); 6.82-6.98 m (5H); 7.01 dd (J = 8.2 Hz, 1H); 7.17 d (J = 8Hz, 2H); 7.25-7.41 m (5H); 7.57 m (2H); 7.82 d (J = 8Hz, 1 H).

b) 4 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol

Prepared from 6- (3-methoxyphenoxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazole according to general formula 6 with addition of 10 mol% hexadecyltributylphosphonium bromide.

1 H-NMR (d 6 -DMSO): δ (ppm): 2.38 s (3H); 6.61 d (J = 2Hz, 1 H); 6.74 d (J = 8Hz, 2H); 6.86 d (J = 8Hz, 2H); 6.91-7.01 m (2H); 7.22-7.41 m (6H); 7.49 m (2 H); 7.75 d (J = 8Hz, 1H); 9.32 s (1 H).

4- [4 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] butanoic acid methyl ester

It is prepared by reacting 4 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol with 4-bromobutyric acid methyl ester according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 2.03-2.16 m (2H); 2.42 s (3H); 2.53 t (J = 7.5Hz, 2H); 3.69 s (3H); 3.97 t (J = 7.5Hz, 2H); 6.78-6.94 m (5H); 6.99 dd (J = 8.2 Hz, 1H); 7.16 d (J = 8Hz, 2H); 7.24-7.38 m (5H); 7.57 m (2H); 7.79 d (J = 8Hz, 1 H).

Example 182

4 - [[1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] acetic acid methyl ester

It is prepared by reacting 4 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol with methyl bromoacetate according to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 2.43 s (3H); 3.82 s (3H); 4.61 s (2H); 6.78-6.96 m (5H); 7.00 dd (J = 8.2 Hz, 1H); 7.14 d (J = 8Hz, 2H); 7.23-7.38 m (5H); 7.56 m (2 H); 7.80 d (J = 8Hz, 1H).

Example 183

4 - ((1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] butanoic acid methyl ester

Obtained from 1,2-diphenyl-6-hydroxy-1H-benzimidazole and 4-bromobutanoic acid methyl ester according to the general formula 8.

T. t. Mp 107-110 ° C.

Example 184

6 [[2-Phenyl-1- (3-pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6 - [[2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester with pyridine-3-boronic acid according to the general formula 14.

MS (EI): 415 (molecular ion).

Example 185

6 - [[2-Phenyl-1- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6 - [[2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester with pyridine-3-boronic acid according to the general formula 14.

MS (EI): 415 (molecular ion).

Example 186

6 - [[2-Phenyl-1- (2-pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid

Prepared by reaction of 6 - [[2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester with 2-fluoropyridine according to the general formula 15.

MS (EI): 401 (molecular ion).

Example 187

6 - [[2-Phenyl-1- (2-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepared by reaction of 6 - [[2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester with 2-fluoropyridine according to the general formula 15.

MS (EI): 401 (molecular ion).

Example 188

6 - [[2-Phenyl-1- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid with pyridine-4-boronic acid according to the general formula 14.

MS (EI): 415 (molecular ion).

Example 189

6 - [[2- (4-Fluorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[4-amino-3- (phenylamino) phenyl] oxy] hexanoate with 4-fluorobenzoyl chloride according to general formula 5.

MS (EI): 432 (molecular ion).

Example 190

6 - [[2- (4-Methoxyphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[4-amino-3- (phenylamino) phenyl] oxy] hexanoate with 4-methoxybenzoyl chloride according to general formula 5.

MS (EI): 444 (molecular ion).

Example 191

6 - [[2- (3-Fluorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of 6 - [[4-amino-3- (phenylamino) phenyl] oxy] hexanoic acid methyl ester with 3-fluorobenzoyl chloride according to general formula 5.

MS (EI): 432 (molecular ion).

Example 192

6 - [[2- (4-Bromophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[4-amino-3- (phenylamino) phenyl] oxy] hexanoate with 4-bromobenzoyl chloride according to general formula 5.

MS (EI): 492/494 (molecular ions).

Example 193

6 - [[2- [4- (Trifluoromethyl) phenyl] -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared by reaction of methyl 6 - [[4-amino-3- (phenylamino) phenyl] oxy] hexanoic acid with 4- (trifluoromethyl) benzoyl chloride according to general formula 5.

MS (EI): 482 (molecular ion).

Example 194

6 - [[2- (4-Fluorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Obtained from 6 - [[2- (4-fluorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester according to the general formula 9.

MS (EI): 418 (molecular ion).

Example 195

6 - [[1-Phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is prepared by reacting 6 - [[4-amino-3- (phenylamino) phenyl] oxy] hexanoic acid methyl ester with benzothiophene-2-carboxylic acid chloride according to general formula 5.

T. t. Mp 129-130 ° C.

Example 196

6 - [[1-Phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. 340 ° C (dec.).

Example 197

6 - [[5-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

Example 198

6 - [[6-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid isopropyl ester

4,5-Dimethoxy-1,2-dinitrobenzene is hydrogenated according to general formula 1 to a diamino compound which is cyclized as a crude product of general formula 3 with trimethyl orthobenzoate to give 5,6-dimethoxy-2-phenyl-1H-benzimidazole ( mp 131-133 ° C). This benzimidazole derivative is reacted with 4-methylphenylboronic acid according to general formula 14 to give 5,6-dimethoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole (m.p. 145-148 ° C). This was cleaved with hydrobromic acid according to general formula 6 to give 5,6-dihydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole (1 H-NMR of hydrobromide (de-DMSO): δ (ppm): 2 42 s (3H); 6.68 s (1H); 7.22 s (1H); 7.40-7.62 m (10H)) which is then alkylated according to general formula 8 with isopropyl 6-bromohexanoate. There was thus obtained 6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester,

1.1. 137-139 ° C, and 6 - [[6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid isopropyl ester,

1.1. Mp 177-178 ° C.

Example 199

6 - [[5-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 245-248 ° C.

Example 200

6 - [[6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

Mp 1.182-184 ° C.

Example 201

6 - [[5-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

6 - [[5-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is methylated with methyl iodide according to General Regulation 8.

T. t. Mp 89-91 ° C.

Example 202

6 - [[5-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 184-186 ° C.

Example 203

6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Example 204

6 - [[6-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

Esters are prepared analogously to the corresponding isopropyl esters by alkylation of 5,6-dihydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general formula 8. The 6 - [[5- hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexane, 1 H-NMR (CDCl ₃ ): δ (ppm): 1.45-1.58 m (2H ); 1.65-1.90 m (4H); 2.37 t (J = 7.5Hz, 2H); 2.48 s (3H); 3.68 s (3H); 3.98 t (1 = 7.5 Hz, 2H); 5.68 s br (lH, OH); 6.62 s (1H); 7.18 d (J = 8Hz, 2H); 7.22-7.38 m (5H); 7.40 s (lH); 7.53 dd (J = 8.1 Hz, 2H), and 6 - [[6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester,

1.1. Mp 141-143 ° C.

Example 205

6 - [[5-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester mg 6 - [[5-methoxy-1- (4-methylphenyl)] Dissolve -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid in 2 mL of methanol, add 1 drop of concentrated sulfuric acid and stir for 2 hours. Saturated potassium bicarbonate solution was added, the mixture was diluted with water, extracted with ethyl acetate, the extracts dried over sodium sulfate and concentrated in vacuo. The evaporation residue is crystallized from diisopropyl ether.

T. t. Mp 81-82 ° C.

Example 206

6 - [[6-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

6 - [[6-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid is methylated with methyl iodide according to General Regulation 8.

T. t. Mp 108-110 ° C.

Example 207

6 - [[6-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 182-184 ° C.

Example 208

6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

a) 3 - [(3,4-Dimethylphenyl) amino] -4,6-dinitrophenol

To a suspension of 4 g of 4,6-dinitro-3-fluorophenol (J. Org. Chem. 1991, 5958) in 100 ml of ethanol was added 6.6 g of 3,4-dimethylaniline and the mixture was allowed to stir at 40 ° C for 7 days. After cooling, the reaction mixture is filtered off with suction and the residue is recrystallized from ethanol.

1 H-NMR (CDCl ₃ ): δ (ppm): 2.20 s (6H); 6.43 s (1H); 6.90-7.0 m (2H); 7.14 d (J = 8Hz, 1H); 9.08 s (1H);

9.70 with br (1H); 10.2-10.6 (1 H).

b) 6 - [[3 - [(3,4-Dimethylphenyl) amino] -4,6-dinitrophenyl] oxy] hexanoic acid methyl ester

5.0 g of 3 - [(3,4-dimethylphenyl) amino] -4,6-dinitrophenol is O-alkylated with methyl 6-bromohexanoate at 70 ° C analogously to General Regulation 8.

1 H-NMR (CDCl 3): δ (ppm): 1.45-1.88 m (6H); 2.30 s (6H); 2.33 t (J = 7.5Hz, 2H); 3.68 s (3H); 3.88 t (J = 7.5Hz, 2H); 6.45 s (1H); 7.00-7.08 m (2H); 7.25 d (J = 8Hz, 1H); 9.03 s (1H); 9.89 with br (1H).

c) 6 - [(5-Amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

2.45 g of 6 - [[3 - [(3,4-dimethylphenyl) amino] -4,6-dinitrophenyl] oxy] hexanoic acid methyl ester is hydrogenated in methanol according to general formula 1 and 500 mg of the crude product is reacted with benzimidate hydrochloride according to general formula 4, except that the crude product is not washed with aqueous hydrochloric acid after removal into the solvent.

1 H-NMR (CDCl 3): δ (ppm): 1.48-1.58 m (2H); 1.62-1.78 m (2H); 1.78-1.90 m (2 H); 2.30 s (3H); 2.38 s (3H); 2.38 t (J = 7.5Hz, 2H); 3.67 s (3H); 3.93 t (J = 7.5Hz, 2H); 6.56 s (1H); 6.98-7.08 m (2H); 7.18 s (1H); 7.20-7.32 m (4H); 7.52 dd (J = 8.2 Hz, 2H).

Example 209

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-Amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 186-191 ° C.

Example 210

6 - [(5-amino-2- (4-fluorophenyl) -1- (4-methoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared in an analogous manner to methyl 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoate.

MS (EI): 477 (molecular ion).

Example 211

6 - [(5-amino-1- (4-methoxyphenyl) -2- (4-methoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared in an analogous manner to methyl 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoate.

MS (EI): 489 (molecular ion).

Example 212

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -2- (4-fluorophenyl) -1- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-Amino-2- (4-fluorophenyl) -1- (4-methoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is reacted with 4-chlorobenzenesulfonic acid chloride according to the general procedure of Regulation 13.

T. t. Mp 180-182 ° C.

Example 213

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-amino-1- (4-methoxyphenyl) -2- (4-methoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13th

T. t. Mp 169-171 ° C.

Example 214

4 - [(5-amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] butanoic acid methyl ester

Prepared in an analogous manner to 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-methyl) -methyl ester

benzimidazol-6-yl) oxy] hexanoic acid.

1 H-NMR (CDCl 3): δ (ppm): 2.17 tt (J = 8.8 Hz, 2H); 2.52 t (J = 8Hz, 2H); 3.68 s (3H); 3.90 s (3H); 3.98 t (J = 7.5Hz, 2H); 6.54 s (1H); 7.0 d (J = 12Hz, 2H); 7.18-7.35 m (6H); 7.50-7.58 m (2 H).

Example 215

4 - [[5 - [[(4-Chloro-phenyl) -sulfonyl] -amino] -1- (4-methoxy-phenyl) -2-phenyl-1H-benzimidazol-6-yl-oxo] -butanoic acid methyl ester

4 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] butanoic acid methyl ester is reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

MS (EI): 605 (molecular ion).

Example 216

5 - [(5-amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester

Prepared in analogy to 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester.

1 H-NMR (CDCl 3): δ (ppm): 1.78-1.89 m (4H); 2.321 (J = 8Hz, 2H); 3.68 s (3H); 3.88 s (3H); 3.921 (l = 7.5 Hz, 2H); 6.53 s (1H); 7.0 d (J = 12 Hz, 2H); 7.18-7.36 m (6H); 7.48-7.58 m (2H).

Example 217

5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester

5 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester is reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

MS (EI): 619 (molecular ion).

Example 218

6 - [(5-amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared in analogy to 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester.

T. t. 129-131 [deg.] C.

Example 219

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester was reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 168-170 ° C.

Example 220

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 181-182 ° C.

Example 221

6 - [(5-amino-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester

Prepared in analogy to 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester.

T. t. 105-107 ° C.

Example 222

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-amino-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester was reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 189-191 ° C.

Example 223

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 102-105 ° C.

Example 224

5 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester

Prepared in analogy to 6 - [(5-amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester.

1 H-NMR (CDCl 3): δ (ppm): 1.82-1.95 m (4H); 2.391 (J = 8Hz, 2H); 3.69 s (3H); 3.92-4.00 m (2H); 6.60 s (1 H); 7.26-7.34 m (6H); 7.43-7.58 m (5H).

Example 225

5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester

5 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester was reacted with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 157-161 ° C.

Example 226

5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 236-242 ° C.

Example 227

6 - [[5 - [[(4-Fluorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester was reacted with 4-fluorobenzenesulfonic acid chloride according to the general formula 13.

MS (EI): 617 (molecular ion).

Example 228

6 - [[5 - [[(4- (trifluoromethyl) phenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

6 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester was reacted with 4- (trifluoromethyl) benzenesulfonic acid chloride according to the general formula 13.

MS (EI): 668 (molecular ion).

Example 229

6 - [[5 - [[(4- (Trifluoromethyl) phenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 190-192 ° C.

Example 230

6 - [[5 [[(4-chlorophenyl) sulfonyl] methylamino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

To a solution of 100 mg of 6 - [[5 - [[(4-chlorophenyl) -sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester in 3 ml of tetrahydrofuran was added at 0 ° C to 10 mg of sodium hydride. After stirring for 30 minutes, 50 µL of methyl iodide is added dropwise and stirred for an additional 60 minutes at 0 ° C. The mixture is quenched with ammonium chloride solution, extracted 3 times with ethyl acetate, the organic phases are washed with water, dried over sodium sulphate, evaporated in vacuo and the residue chromatographed on silica gel.

T. t. 178-180 ° C.

Example 231

[[(4-chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] acetic acid methyl ester

To a suspension of 100 mg of 4-chloro-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide in 0.5 ml of N, N-dimethylformamide was added 8 mg of sodium hydride and stirred at room temperature for 30 minutes. Noc: 18 ° C. 50 mg of methyl bromoacetate is added, the mixture is stirred for 15 hours, quenched with water and extracted 3 times with ethyl acetate. After drying over sodium sulfate, it is concentrated in vacuo and the residue is chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ (ppm): 3.70 s (3H); 4.52 s (2H); 7.20 d (J = 8Hz, 1H); 7.26-7.58 m (14H); 7.70 d (J = 10Hz, 2H).

Example 232

[[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] acetic acid

Prepare in accordance with General Regulation 9.

T. t. 248 ° C.

Example 233

4 - [[(4-chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] butanoic acid methyl ester

100 mg of 4-chloro-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide were suspended in 0.5 ml of N, N-dimethylformamide. 6 mg of sodium hydride was added to the suspension, and the mixture was stirred at 20 ° C for 30 minutes. 56 mg of 4-bromobutyric acid methyl ester is then added, the mixture is stirred for 15 hours, quenched with water and extracted three times with ethyl acetate. After drying over sodium sulfate, the combined extracts are concentrated in vacuo and the residue digested with diisopropyl ether.

T. t. Mp 54-58 ° C.

Example 234

4 - [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] butanoic acid

Obtained according to General Regulation 9.

T. t. Mp 249-254 ° C.

Example 235

5 - [[(4-Chloro-phenyl) -sulfonyl] [1,2-diphenyl-1H-benzoimidazol-5-yl] -amino] -pentanoic acid methyl ester

100 mg of 4-chloro-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide are suspended in 0.5 ml of N, N-dimethylformamide, 8 mg of sodium hydride are added to the suspension and stirred 30 minutes at 20 ° C. 60 mg of 5-bromopentanoic acid methyl ester was added and the mixture was stirred for 15 hours, then quenched with water and extracted three times with ethyl acetate. The extracts are dried over sodium sulfate, concentrated in vacuo and the residue subjected to silica gel chromatography.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.46-1.54 m (2H); 1.62-1.78 m (2H); 2.30 t (J = 8Hz, 2H); 3.62 s (3H); 3.62 t (J = 8Hz, 2H); 7.12-7.53 m (17H).

Example 236

5 - [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] pentanoic acid

Obtained according to General Regulation 9.

T. t. Mp 123-127 ° C.

Example 237

6 - [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid methyl ester

Prepared by reaction of 6 - [[1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid methyl ester with 4-chloro-benzenesulfonic acid chloride according to General Regulation 13.

MS (EI): 588 (molecular ion).

Example 238

7 - [[(4-Chloro-phenyl) -sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] -amino] -heptanoic acid methyl ester

100 mg of 4-chloro- N - (1,2-diphenyl-1 H -benzoimidazol-5-yl) benzenesulfonamide are suspended in 0.5 ml of M-dimethyl dimethyl form, 8 mg of sodium hydride are added to the suspension. and stirred at 20 ° C for 30 minutes. 70 mg of 7-bromoheptanoic acid methyl ester was added and the mixture was stirred for 15 hours, then quenched with water and extracted three times with ethyl acetate. The extracts are dried over sodium sulfate, concentrated in vacuo and the residue subjected to silica gel chromatography.

1 H-NMR (CDCl 3): δ (ppm): 1.26-1.64 m (8H); 2.271 (J = 8Hz, 2H); 3.601 (J = 8Hz, 2H); 3.68 s (3H); 7.12 dd (J = 10.2 Hz, 1H); 7.22 d (J = 10Hz, 1H); 7.30-7.61 m (15H).

Example 239

7 - [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] heptanoic acid

Obtained according to General Regulation 9.

T. t. Mp 172-178 ° C.

Example 240 N- (1,2-Diphenyl-1H-benzimidazol-5-yl) -4-fluorobenzenesulfonamide

Prepared by reacting 5-amino-1,2-diphenyl-1H-benzimidazole with 4-fluorobenzenesulfonic acid chloride according to general procedure 13.

T. t. Mp 209-214 ° C.

Example 241

6 - [[(4-Fluorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid methyl ester

150 mg of N- (1,2-diphenyl-1H-benzimidazol-5-yl) -4-fluorobenzenesulfonamide are suspended in 0.5 ml of Ν, Ν-dimethylformamide, 12 mg of sodium hydride are added thereto, and the mixture is stirred for 30 minutes. minutes at 20 ° C. 98 mg of 6-bromohexanoic acid methyl ester was added and the mixture was stirred for 15 hours, then quenched with water and extracted three times with ethyl acetate. The extracts were dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

T. t. Mp 128-134 ° C.

Example 242

6 - [[(4-Fluorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid

Obtained according to General Regulation 9.

T. t. 200-210 ° C.

Example 243

6 - [[[4- (Trifluoromethyl) phenyl] sulfonyl] - [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid methyl ester

150 mg of 4- (trifluoromethyl) - [7- (1,2-diphenyl-1H-benzimidazol-5-yl) -benzenesulfonamide is suspended in 0.5 ml of Ν, Ν-dimethylformamide, 11 mg of sodium hydride are added to the suspension, and Stir for 30 minutes at 20 ° C. 88 mg of 6-bromohexanoic acid methyl ester is added and the mixture is stirred for 15 hours, then quenched with water and extracted three times with ethyl acetate. The extracts were dried over sodium sulfate, the solvent was evaporated in vacuo and the residue digested with diisopropyl ether.

T. t. 159-161 ° C.

Example 244

6 - [[[4- (Trifluoromethyl) phenyl] sulfonyl] - [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid

Obtained according to General Regulation 9.

T. t. Mp 224-230 ° C.

Example 245

4-Chloro-N- [1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-5-yl] benzenesulfonamide

a) (2,4-Dinitrophenyl) (4-methoxyphenyl) amine

A mixture of 1.43 g of 4- (2,4-dinitroaniline) phenol, 500 mg of potassium carbonate, 0.32 ml of methyl iodide and 5 ml of N, N-dimethylformamide was allowed to stir for 2 days at 20 ° C. The mixture was poured into water, extracted three times with ethyl acetate, dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

T. t. Mp 117-127 ° C.

b) 5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazole (2,4-dinitrophenyl) (4-methoxyphenyl) amine is hydrogenated according to general formula 1 and the crude product is cyclized with trimethyl ortobenzoate to the benzimidazole derivative according to General Regulation 3.

1 H-NMR (CDCl 3): δ (ppm): 3.88 s (3H); 6.70 dd (J = 12.2 Hz, 1H); 6.95-7.06 m (4H); 7.18-7.38 m (7H);

7.53-7.65 m (2 H).

c) 4-Chloro-N- [1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-5-yl] -benzenesulfonamide

It is prepared by reacting 5-amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazole with 4-chlorobenzenesulfonic acid chloride according to the general formula 13.

T. t. Mp 238-240 ° C.

Example 246

6 - [[(4-Chloro-phenyl) -sulfonyl] - [1- (4-methoxy-phenyl) -2-phenyl-1H-benzimidazol-5-yl] -amino] -hexanoic acid methyl ester

To a suspension of 75 mg of 4-chloro-N- [1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-5-yl] benzenesulfonamide in 0.5 ml of Ν, Ν-dimethylformamide was added 6 mg of sodium hydride and stirred at 30 ° C for 30 minutes. After addition of 44 mg of methyl 6-bromohexanoate, the mixture was stirred for 15 hours, quenched with water and extracted three times with ethyl acetate. The extracts were dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

MS (EI): 617 (molecular ion).

Example 247

6 - [[(4-chlorophenyl) sulfonyl] - [1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-5-yl] amino] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. 205-208 ° C.

Example 248

2,2-Dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

a) 2,2-Dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanenitrile

It is prepared by reacting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromo-1,1-dimethylhexanenitrile according to the general formula 8.

T. t. Mp 115-118 ° C.

b) 2,2-Dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

500 mg of 2,2-dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanenitrile was refluxed for 2 hours with 5 ml of 80% sulfuric acid. After cooling, the reaction mixture was poured carefully into ice water, adjusted to pH 8 by addition of sodium hydroxide, and extracted three times with ethyl acetate. The extracts were dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

T. t. Mp 115-118 ° C.

Example 249

8 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -octanoic acid methyl ester

Prepared by the reaction of 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 8-bromooctanoic acid methyl ester according to general procedure 8.

T. t. Mp 92-95 ° C.

Example 250

8 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] octanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 136-140 ° C.

Example 251

6 - [[1- (Indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared in analogy to 6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester.

T. t. Mp 81-85 ° C.

Example 252

6 - [[1- (Indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. 176-180 ° C.

Example 253

7 - [[1- (Indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] heptanoic acid methyl ester

Prepared in an analogous manner to methyl 6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester.

T. t. Mp 92-98 ° C.

Example 254

7 - [[1- (Indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] heptanoic acid

Prepare in accordance with General Regulation 9.

T. t. 175-178 ° C.

Example 255

6 - [[1- (3-Fluorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared in an analogous manner to methyl 6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester.

T. t. Mp 104-106 ° C.

Example 256

6 - [[1- (3-Fluorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. Mp 149-151 ° C.

Example 257

6 - [[2- (4-Nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

a) 6-Methoxy-2- (4-nitrophenyl) -1-phenyl-1H-benzimidazole

200 mg of 4-methoxy-N ² -phenyl-o-phenylenediamine are dissolved in 5 ml of N, N -dimethylformamide, 346 mg of EEDQ and 234 mg of 4-nitrobenzoic acid are added and stirred at 100 ° C for 5 hours. After cooling, the mixture is quenched with water, the precipitate is filtered off with suction and purified by silica gel column chromatography. It is then taken up in 6N hydrochloric acid and heated under reflux for 2 hours. After cooling, it is added dropwise to a saturated solution of potassium bicarbonate. The precipitate formed is filtered off with suction and dried.

T. t. Mp 189-191 ° C.

b) 6-Hydroxy-2- (4-nitrophenyl) -1-phenyl-1H-benzimidazole

Prepare in accordance with General Regulation 6.

1 H-NMR (d 6 -DMSO): δ (ppm): 6.56 d (J = 2 Hz, 1H); 6.87 dd (J = 10.2 Hz, 1H); 7.46 dd (J = 10.2 Hz, 2H);

7.53-7.70 m (4H); 7.75 d (J = 10Hz, 2H); 8.20 d (J = 10Hz, 2H); 9.55 with br (1H).

c) 6 - [[2- (4-Nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepare in accordance with General Regulation 8.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.45-1.55 m (2H); 1.62-1.84 m (4H); 2.33 t (J = 8Hz, 2H); 3.68 s (3H); 3.95 t (J = 8Hz, 2H); 6.67 d (J = 2Hz, 1 H); 7.00 dd (J = 10.2 Hz, 1H); 7.28-7.38 m (2H); 7.52-7.60 m (3H); 7.71 d (J = 10Hz, 2H); 7.77 d (J = 10Hz, 1H); 8.13 d (J = 10Hz, 2H).

Example 258

6 - [[2- (4-Nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

Prepare in accordance with General Regulation 9.

T. t. 181-186 ° C.

Example 259

6 - [[1-Phenyl-2- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

Prepared in analogy to 6 - [[1-phenyl-2- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester.

T. t. Mp 159-160 ° C.

Example 260

N- (Cyclopropylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

MS (EI): 469 (molecular ion).

Example 261

N-Isobutoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

MS (EI): 471 (molecular ion).

Example 262 N- (Phenylmethoxy) -6 - [(2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide

To a solution of 17 mg of carbonyldiimidazole in 1 ml of tetrahydrofuran is added a solution of 50 mg of 6 - [(2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanoic acid in 1 ml of tetrahydrofuran and the mixture is stirred for 30 minutes at 20 ° C and then for 30 minutes at reflux. 16 mg of O-benzylhydroxylamine hydrochloride are added at 20 ° C and the mixture is stirred for 20 hours. Ethyl acetate was then added and the mixture was extracted with 2 N hydrochloric acid and saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography.

T. t. Mp 145-148 ° C.

Example 263 N- (Cyclopropylmethoxy) -6 - [(2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide

Prepared in analogy to N - (phenylmethoxy) -6 - [(2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide.

MS (EI): 559 (molecular ion).

Example 264

N-isobutoxy-6 - [(2-phenyl-l- (3,4,5-trimethoxy-phenyl) -lH-benzimidazol-6-yl) oxy] hexanamide

Prepared in analogy to M (phenylmethoxy) -6 - [(2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide.

1 H-NMR (CDCl ₃ ): δ (ppm): 0.94 d (J = 8 Hz, 6H); 1.48-2.03 m (7H); 2.05-2.18 m (2H); 3.60-3.72 m (2H); 3.76 s (6H); 3.90-4.00 m (2H); 3.96 s (3H); 6.50 s (2H); 6.72 d (J = 2Hz, 1 H); 6.95 dd (J = 10.2 Hz, 1H); 7.28-7.38 m (3H); 7.55-7.62 m (2H); 7.74 d (J = 10Hz, 1H); 8.20 with br (1H).

Example 265

N-Isopropyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 17.

T. t. Mp 107-112 ° C.

Example 266 / N, N-Dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 17.

T. t. Mp 83-88 ° C.

Example 267

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-pyrrolidin-1-yl-hexan-1-one

Prepare in accordance with General Regulation 17.

T. t. Mp 84-88 ° C.

Example 268

N- (2-methoxyethyl) -6 - [(l, 2-diphenyl-lH-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 17.

T. t. 63-68 ° C.

Example 269

N- (3-Methoxypropyl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. Mp 84-91 ° C.

Example 270

N-isobutyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 17.

1 H-NMR (CDCl ₃ ): δ (ppm): 0.90 d (J = 8 Hz, 6H); 1.44-1.57 m (2H); 1.65-1.85 m (2H); 2.20 t (J = 8Hz, 2H); 3.08 t (J = 8Hz, 2H); 3.94 t (J = 8Hz, 2H); 6.68 d (J = 2Hz, 1 H); 6.96 dd (J = 10.2 Hz, 1H); 7.25-7.38 m (5H); 7.45-7.58 m (5H); 7.75 d (J = 10Hz, 1 H).

Example 271 N - [(2,2-Dimethylamino) ethyl] -N-methyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 17.

1 H-NMR (CDCl ₃ ) (major rotamer signals): δ (ppm): 1.44-1.57 m (2H); 1.64-1.84 m (4H); 2.30 s (6H); 2.34 t (J = 8Hz, 2H); 2.47 t (J = 8Hz, 2H); 3.00 s (3H); 3.50 t (J = 8Hz, 2H); 3.94 t (J = 8Hz, 2H); 6.69 d (J = 2Hz, 1 H); 6.96 dd (J = 10.2 Hz, 1H); 7.25-7.36 m (5H); 7.45-7.56 m (5H); 7.73 d (J = 10Hz, 1H).

Example 272 N- (Methoxyethyl) -N-methyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 17.

1 H-NMR (CDCl ₃ ) (major rotamer signals): δ (ppm): 1.43-1.58 m (2H); 1.63-1.84 m (4H); 2.33 t (J = 8Hz, 2H); 3.07 s (3H); 3.32 s (3H); 3.47-3.58 m (4H); 3.95 t (J = 8Hz, 2H); 6.70 d (J = 2Hz, 1H); 6.96 dd (J = 10.2 Hz, 1H); 7.25-7.35 m (5H); 7.45-7.55 m (5H); 7.75 d (J = 10Hz, 1 H).

Example 273

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-morpholin-1-yl-hexan-1-one

Prepare in accordance with General Regulation 17.

H-NMR (CDC1 _3): δ (ppm): L, 47-L, 59 m (2H); 1.63-1.88 m (4H); 2.34 t (J = 8Hz, 2H); 3.42-3.49 m (2H); 3.57-3.70 m (6H); 3.94 t (J = 8Hz, 2H); 6.68 d (J = 8Hz, 1H); 6.96 dd (J = 10.2 Hz, 1H); 7.23-7.38 m (5H); 7.45-7.56 m (5H); 7.75 d (J = 10Hz, 1 H).

Example 274

7V, 7V-di (2-methoxyethyl) -6 - [(l, 2-diphenyl-lH-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. 88-98 [deg.] C.

Example 275

N-Isopentyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. 127-129 ° C.

Example 276

N - (Pyrid-2-yl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. Mp 120-124 ° C.

Example 277

77- (Pyrid-3-yl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. 154 [deg.] C.

Example 278

6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-piperidin-1-yl-hexan-1-one

Prepare in accordance with General Regulation 18.

T. t. Mp 93-98 ° C.

Example 279 [6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-hexanoyl] piperidine-4-carboxamide

Prepare in accordance with General Regulation 17.

T. t. Mp 177-178 ° C.

Example 280

[[6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) -oxy] -1-hexanoyl] methylamino] acetic acid ethyl ester

Prepare in accordance with General Regulation 17.

1 H-NMR (CDCl ₃ ) (major rotamer signals): δ (ppm): 1.23 t (J = 8 Hz, 3H); 1.45-1.88 m (6H); 2.40 t (J = 8Hz, 2H); 3.08 s (3H); 3.93 t (J = 8Hz, 2H); 4.12 s (2H); 4.18 q (J = 8Hz, 2H); 6.70 d (J = 2Hz, 1H); 6.97 dd (J = 10.2 Hz, 1H); 7.23-7.35 m (5H); 7.45-7.58 m (5H); 7.75 d (J = 10Hz, 1 H).

Example 281

4 - [[6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-hexanoyl] piperazine-1-carboxylic acid ethyl ester Prepared according to the general formula 17.

1 H-NMR (CDCl 3): δ (ppm): 1.27 t (J = 8 Hz, 3H); 1.45-1.60 m (2H); 1.63-1.88 m (4H); 2.36 t (J = 8Hz, 2H); 3.40-3.53 m (6H); 3.56-3.64 m (2H); 3.93 t (J = 8Hz, 2H); 4.15 q (J = 8Hz, 2H); 6.69 d (J = 2Hz, 1 H); 6.96 dd (J = 10.2 Hz, 1H); 7.23-7.38 m (5H); 7.45-7.56 m (5H); 7.76 d (J = 10Hz, 1 H).

Example 282

N-Isopropyl-6 - [[l- (3,4-dimethyl-phenyl) -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

MS (EI): 469 (molecular ion).

Example 283 / N, N-Dimethyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

MS (EI): 455 (molecular ion).

Example 284

N, 7V-diethyl-6 - [[l- (3,4-dimethyl-phenyl) -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

MS (EI): 483 (molecular ion).

Example 285

7V-Isobutyl-6 - [[l- (3,4-dimethyl-phenyl) -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl 3): δ (ppm): 0.90 d (J = 8 Hz, 6H); 1.44-1.55 m (2H); 1.58-1.83 m (5H); 2.20 t (J = 8Hz, 2H); 2.30 s (3H); 2.35 s (3H); 3.09 t (J = 8Hz, 2H); 3.94 t (J = 8 Hz, 2H); 6.63 d (J = 2Hz, 1 H); 6.94 dd (J = 10.2 Hz, 1H); 7.02 dd (J = 10.2 Hz, 1H); 7.10 d (J = 2Hz, 1 H); 7.22-7.35 m (4H); 7.56 dd (J = 8.2 Hz, 2H); 7.73 d (J = 10Hz, 1 H).

Example 286 N-Cyclopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

MS (EI): 467 (molecular ion).

Example 287

7V-cyclobutyl-6 - [[l- (3,4-dimethyl-phenyl) -2-phenyl-lH-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.42-1.55 m (2H); 1.60-1.88 m (8H); 2.15 t (J = 8Hz, 2H); 2.28-2.40 m (2H);

2.30 s (3H); 2.35 s (3H); 3.93 t (J = 8Hz, 2H); 4.40 quintet (J = 8 Hz, 2H); 5.55 with br (1H); 6.63 d (J = 2Hz, 1 H);

6.92 dd (J = 10.2 Hz, 1H); 7.03 dd (J = 10.2 Hz, 1H); 7.08 d (J = 2Hz, 1 H); 7.20-7.36 m (4H); 7.57 dd (J = 8.2Hz, 2H); 7.72 d (J = 10Hz, 1 H).

Example 288

N- 7-tert-butyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.32 s (9H); 1.42-1.55 m (2H); 1.62-1.82 m (4H); 2.101 (J = 8Hz, 2H); 2.30 s (3H); 2.36 s (3H); 3.92 t (J = 8Hz, 2H); 5.23 with br (1H); 6.66 d (J = 2Hz, 1 H); 6.93 dd (J = 10.2 Hz, 1H); 7.02 dd (J = 10.2 Hz, 1H); 7.09 with br (1H); 7.22-7.36 m (4H); 7.56 dd (J = 8.2Hz, 2H); 7.73 d (J = 10Hz, 1 H).

Example 289 (R) -6 - [[1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -1- (2-methoxymethyl) pyrrolidin-1-yl-hexane- 1 -ón

Prepare in accordance with General Regulation 18.

MS (EI): 467 (molecular ion).

Example 290

N - (3-Imidazol-1-yl-propyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl 3): δ (ppm): 1.42-1.53 m (2H); 1.62-2.02 m (6H); 2.17 t (J = 8Hz, 2H); 2.27 s (3H); 2.34 s (3H); 3.24 q (J = 8Hz, 2H); 3.92 t (J = 8Hz, 2H); 3.96 t (J = 8Hz, 2H); 5.68 with br (1H); 6.63 d (J = 2Hz, 1 H); 6.88-6.95 m (2 H); 7.00 dd (J = 10.2 Hz, 1H); 7.04-7.10 m (2H); 7.20-7.36 m (4H); 7.50 s br (lH); 7.53 dd (J = 8.2 Hz, 2H); 7.72 d (J = 10Hz, 1 H).

Example 291 N- (2-Pyrid-2-yl-ethyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl ₃ ): δ (ppm): 1.38-1.52 m (2H); 1.62-1.82 m (4H); 2.15 t (J = 8Hz, 2H); 2.30 s (3H); 2.35 s (3H); 2.96 t (J = 8Hz, 2H); 3.66 q (J = 8Hz, 2H); 3.90 t (J = 8Hz, 2H); 6.48 with br (1H); 6.65 d (J = 2Hz, 1 H);

6.92 dd (J = 10.2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7.06-7.38 m (7H); 7.53-7.62 m (3H); 7.72 d (J = 10Hz, 1H); 8.50 d br (J = 6Hz, 1H).

Example 292

N ^, N-Dimethyl-6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl 3): δ (ppm): 1.46-1.58 m (2H); 1.64-1.88 m (4H); 2.32 t (J = 8Hz, 2H); 2.93 s (3H); 3.00 s (3H); 3.96 t (J = 8Hz, 2H); 6.65 d (J = 2Hz, 1 H); 7.00 dd (J = 10.2 Hz, 1H); 7.28-7.36 m (2H); 7.53-7.61 m (3H); 7.70 d (J = 10Hz, 2H); 7.76 d (J = 8Hz, 1H); 8.13 d (J = 8Hz, 2H).

Example 293

N-Isopropyl-6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

Mp 162-165 ° C.

Example 294 N -isopentyl-6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. Mp 148-154 ° C.

Example 295 A ^/ - (3-methoxypropyl) -6 - [[2- (4-nitrophenyl) -l-phenyl-lH-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

T. t. M.p. 104-110 ° C.

Example 296 N- (3-Methoxypropyl) -6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

Prepare in accordance with General Regulation 18.

1 H-NMR (CDCl 3): δ (ppm): 1.43-1.56 m (2H); 1.62-1.85 m (6H); 2.10-2.23 m (4H); 2.95 t (J = 10Hz, 2H); 3.00 t (J = 10Hz, 2H); 3.32 s (3H); 3.32-3.40 m (2H); 3.48 t (J = 8Hz, 2H); 3.93 t (J = 8Hz, 2H); 6.03 with br (1H); 6.67 d (J = 2Hz, 1 H); 6.93 dd (J = 10.2 Hz, 1H); 7.03 dd (J = 10.2 Hz, 1H); 7.12 with br (1H); 7.26-7.35 m (4H); 7.55 dd (J = 10Hz, 2H); 7.72 d (J = 8Hz, 1H).

Example 297

6 - [[1- (4-Methylphenyl) -2- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 3-pyridylcarbaldehyde according to the general formula 16.

MS (EI): 429 (molecular ion).

Example 298

6 - [[1- (4-Methylphenyl) -2- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 4-pyridylcarbaldehyde according to the general formula 16.

MS (EI): 429 (molecular ion).

Example 299

6 - [[1- (4-Methylphenyl) -2- (2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 2-thienylcarbaldehyde according to the general formula 16.

MS (EI): 434 (molecular ion).

Example 300

6 - [[1- (4-Methylphenyl) -2- (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 3-thienylcarbaldehyde according to the general formula 16.

MS (EI): 434 (molecular ion).

Example 301

6 - [[2- (3-Indolyl) -1- (4-methylphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 3-indolylcarbaldehyde according to the general formula 16.

MS (EI): 467 (molecular ion).

Example 302

6 - [[1- (4-Methylphenyl) -2- (2-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 2-furylcarbaldehyde according to the general formula 16.

MS (EI): 418 (molecular ion).

Example 303

6 - [[1- (4-Methylphenyl) -2- (3-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 3-furylcarbaldehyde according to the general formula 16.

MS (EI): 418 (molecular ion).

Example 304

6 - [[1- (4-Methylphenyl) -2- (5-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 5-methyl-2-thienylcarbaldehyde according to the general formula 16.

MS (EI): 448 (molecular ion).

Example 305

6 - [[1- (4-Methylphenyl) -2- (4-bromo-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 4-bromo-2-thienylcarbaldehyde according to the general formula 16.

MS (EI): 512/514 (molecular ions).

Example 306

6 - [[1- (4-Methylphenyl) -2- (3-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

It is obtained by reacting 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] oxy] hexanoic acid methyl ester with 3-methyl-2-thienylcarbaldehyde according to the general formula 16.

MS (EI): 448 (molecular ion).

Example 307

Suppression of microglia activation

For in vitro preparation of β-activated microglia, primary rat microglia are incubated with synthetic β-peptide:

To simulate β-deposits, the synthetic β-peptide is dried in a 96-well culture plate. For this purpose, the 2 mg / ml H ₂ O peptide stock solution is diluted 1: 50 with water. When applied to a 96-well plate, 30 μΐ of this diluted peptide solution is pipetted into each well and allowed to dry overnight at room temperature. .

Primary rat microglia are prepared from mixed glial cultures obtained from rat P3 brains. For the preparation of these mixed glial cultures, the 3 day old rats are harvested and the brain skins removed. Cell release is achieved by trypsinization (0.25% trypsin solution, 15 minutes, 37 ° C). After separating the uncleaved tissue fragments by passing through a 40 µm nylon mesh, the isolated cells are centrifuged (800 rpm, 10 minutes). The cell pellet is suspended in culture medium and transferred to 100 ml culture flasks (1 brain / culture flask). Cells are cultured for 5-7 days in Dulbeccos Modified Eagle Medium (DMEM, glutamine) containing medium containing penicillin (50 U / ml), streptomycin (40 pg / ml) and 10% (v / v). fetal calf serum (FCS) at 37 ° C and 5% CO ₂ . During this incubation, an adhesive cell coating is formed, mainly composed of astrocytes. Microglia proliferate therein as non-adherent or only weakly adherent cells and are discarded after suspension (420 rpm, 1 hour).

To activate β-peptide microglia, 2.5 x 10 ⁴ micro-gels / well are plated in β-peptide coated culture plates and incubated for 7 days in DMEM (with glutamine) containing penicillin (50 U / ml), streptomycin (40 pg / ml) and 10% (v / v) fetal calf serum (FCS) at 37 ° C and 5% CO ₂ . On the fifth day, the compound of the invention is added at various concentrations (0.1, 0.3, 1, 3 and 10 μΜ).

To quantify microglia reactivity, the metabolic activity is measured on day 7 of culture by reduction of MTS (3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (sulfophenyl) -2H-tetrazolium), Owen's Reagent, Baltrop, JA et al., Bioorg. & Med. Chem. Lett. 1, 6111 (1991)). Percent inhibition refers to a control that was treated exclusively with DMSO. The compounds of the invention inhibit the activation of microglia.

Example 308

Stroke in rats (MCAO-model)

The compounds of the invention are tested in an animal model of cerebral ischemia (stroke), the MCAO model ("permanent middle cerebral artery occlusion"), for an in vivo inhibitory effect. Unilateral occlusion of the middle cerebral artery (MCA) induces a cerebral infarction, which is due to an insufficient supply of oxygen and nutrients to the corresponding brain area. As a result, there is a significant cell death along with subsequent activation of the microglia. However, this activation will reach its maximum at the earliest after a few days and may last for several weeks. For testing, the compounds of the invention are administered intraperitoneally 1-6 days after occlusion. On the seventh day, the animals are perished and sacrificed. The extent of microglia activation is measured using a modified immunohistochemical method. For this purpose, the vibratoma sections of fixed brains are incubated with antibodies that recognize the CR3 complement receptor and resp. MHCI1 complex on activated microglia. Quantitation of the primary antibody binding is performed using an enzyme-linked detection system. The addition of the compounds of the invention results in a significant reduction in microglia activation in the hemispheres affected by cerebral infarction. This reduction shall be at least 20%.

Example 309

Activation of macrophages

LPS-activated THP-1 cells are used in the macrophage / monocyte compound assay. For this purpose, 2.5 x ^{10 6} cells / ml RPMI medium (RPMI 1640 + 10% FCS) are seeded. The compounds of the invention are added at a concentration of 5 μΜ and preincubated for 30 minutes. The cells are stimulated overnight at 37 ° C with 1 gg / ml LPS. The medium is then discarded and the amount of TNFα is quantitated. Treatment of cells with the compounds of the invention results in at least a 30% reduction in the amount of TNF [alpha].

PATENT CLAIMS

Claims (26)

Benzimidazole derivatives of the general formula (I) wherein: R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl en-4 heteroatoms selected from the group comprising nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ ', C (NR ⁴ ) NH ₂ , C (NR ⁴ ) NHR ⁴ ', C (NR ⁴ ) NR ⁴ R ⁴ ', XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH ₂ , XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO ₂ NH ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ⁴ , NO ₂ , XNH ₂ , XNHR ^4, XNR ⁴ group R ^4, a group XNHSO2R ^4, XN (SO 2 R ⁴⁾ SO 2 R ^4, SO 2 R ⁴ XNR group ^4, group ⁴ XNHCOR, XNHCOOR group ^4, group XNHCONHR ^4, tetrahydro-2,5-dioxopyrrole-l- yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihyd r-2,7-dioxoisoindol-1-yl or R ⁴ , wherein the two substituents on R ¹ , when in the ortho position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy , propane-1,3-diyl or butane-1,4-diyl, R ² is a mono- or bicyclic C ₆ _i ₀ -aryl or a mono- or bicyclic 5-10-membered heteroaryl en-4 heteroatoms selected from the group comprising nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine, chlorine, bromine, iodine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCOOH, XCOOR ⁴ , XCONH ₂ , XCONHR ⁴ , XCONR ⁴ R ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ^4, a group XSOR ^4, group XSO2R ^4, the group SO 2 NH _2, SO ₂ NHR ^4, SO ₂ NR ⁴ R ⁴ ', a group _NO2, XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ^4, XN ( SO 2 R ⁴⁾ SO 2 R ^4, SO 2 R ⁴ group XNR ^4, tetrahydro-2,5-dioxopyrrole-l-yl, 2,5-dihydro-2,5-dioxopyrrole-l-yl, 2,7-dihydro-2, 7-dioxoisoindol-l-yl or a group R ^4, where two substituents on R ^2, where they are in the ortho position, can be joined together such that they together form methanediylbisoxy, ethane-l, 2-diylbisoxy, propan-1 , 3-diyl or butane-1,462 butyl, R ³ is one or two substituents, which independently of one another may be: hydrogen, fluorine, chlorine, bromine, iodine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR) ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XCOOH, XCOOR ⁴ , XCONH ₂ , XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO2NH ₂ , SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO ₂ R ⁴ , XNR ⁴ SO ₂ R ⁴ , XN (SO ₂ R ⁴ ) (SO ₂ R ⁴ ), XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl or R ⁴ , wherein the two substituents R ³ when they are ortho to each other position, they can be joined together so that they together form me indanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl, R ⁴ and R ^4, independently of one another are C _M -perfluóralkylová group, a C ^ -alkyl, C _{2nd 6} -alkenyl, C _{2nd 6-} alkynyl, C ₃ . ₇ -cycloalkyl, (C |. ₃ alkyl) -C ₃ .7-cycloalkyl, C]. ₃ -alkyl-C ₆ _i ₀ -aryl, C ₃ alkyl substituted 5-10-membered heteroaryl with 1-4 N, S or O, C _{6. A 10-} aryl group or a 5-10-membered heteroaryl group having 1-4 nitrogen, sulfur or oxygen atoms, wherein the aryl and heteroaryl groups may be substituted by one or two substituents from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, a group CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF _3, or C ₂ F ₅ , or may also carry fused methanediyl-bisoxy or ethane-1,2-diyl-bisoxy, and further, in the 5-membered cycloalkyl ring, one member of the ring may be nitrogen or oxygen, and in the 6-membered or 7-membered cycloalkyl ring, one or two members of the ring may be nitrogen and / or oxygen, wherein the nitrogen atoms in the ring may be optionally substituted C _1-4 . _3- alkyl or C _1-3 -alkanoyl, R ⁵ and R ⁵ independently of one another are C _1-6 -alkyl, C ₂ . _6- alkenyl or C ₂ . _6- alkynyl, wherein any carbon atom may be replaced by oxygen, sulfur, SO, SO ₂ , NH, N-C _1-3 -alkyl or NC 1. ₃ -alkanoyl, _C3 _7 cycloalkyl Co_ _3-alkyl group, wherein the five-membered cycloalkyl ring may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members N and / or O, wherein the ring nitrogen The ring may be optionally substituted with a C _1-3 -alkyl group or a C 1-6 alkyl group. _3- alkanoyl, C _{6 O-} aryl or 5-10-membered heteroaryl having 1-4 heteroatoms from the group consisting of nitrogen, sulfur and oxygen, wherein said alkyl, alkenyl and alkynyl chains may be substituted with one of said cycloalkyl, aryl or heteroaryl groups, all of the foregoing alkyl and cycloalkyl groups may be substituted with up to two substituents selected from the group consisting of CF ₃ , C ₂ F 3, OH, OC]. _3- alkyl, NH ₂ groups, NH-C ₁ groups. _3- alkyl, NH-C _1-3 -alkanoyl, N (C _1-3 -alkyl) ₂ , N (C _1-3 -alkyl) (C _1-3 -alkanoyl), COOH, CONH ₂ , COO- C |. _3- alkyl, and all the aforementioned aryl and heteroaryl groups may be substituted by one or two substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, CH ₃ group, C ₂ H ₅ group, NO ₂ group, OCH ₃ , OC ₂ H ₅ , CF ₃ and C ₂ F ₅ groups, or may also carry an fused methanediylbisoxy or ethane-1,2-diyl-bisoxy group, or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7 a membered heterocycle which may contain an additional oxygen, nitrogen or sulfur atom and may be substituted by C 1. _4- alkyl, C _1-4 -alkoxy-C ₀ . ₂ -alkyl, C _{i. 4-} alkoxycarbonyl, aminocarbonyl or phenyl, And a CMO-alkanediyl, C _{2nd 10} -alkanediyl, C ₂ . ₁₀ -alkíndiylová group, a group (C _{0th 5 -alkanediyl-C3} _7-cycloalkanediyl-Co-5 alkanediyl), wherein the five-membered cycloalkyl ring may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members of a nitrogen and / or oxygen atom, wherein the ring nitrogen atoms may be optionally substituted by a C 1-4 -alkyl group or a C _1-3 -alkanoyl group, wherein in the above-mentioned aliphatic chains one or two carbon atoms may be replaced by an oxygen atom, NH, N-C 1. _3- alkyl or N-C _1-3 -alkanoyl, and alkyl or cycloalkyl groups may be substituted by up to two substituents from the group consisting of = O, OH, O-C 1. _3- alkyl, NH ₂ , NH-C _1-3 -alkyl, NH-C 1-4 -alkanoyl, N (C _1-3 -alkyl) ₂ and N / C 1-4 -alkyl (C 1-4 -alkanoyl) groups, B is COOH, COOR ⁵ , CONH ₂ , CONHNH ₂ , CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ , SO ₃ H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO ₂ NR ⁵ R ⁵ ', PO ₃ H, PO (OH) (OR ⁵ ), PO (OR ⁵ ) (OR ⁵ '), PO (OH) (NHR ⁵ ), PO ( NHR ⁵ ) (NHR ⁵ ) or a tetrazolyl group, each of which is bonded to a carbon atom of group A, or the whole of YAB is N (SO ₂ R ⁴ ) (SO ₂ R ⁴ ') or NHSO ₂ R ⁴ , X is a bond, CH ₂ , (CH ₂ ) ₂ , CH (CH ₃ ), (CH ₂ ) ₃ , CH (CH ₂ CH ₃ ), CH (CH ₃ ) CH ₂ , CH ₂ CH (CH _3), Y is O, NH, NR ⁴ , NCOR ⁴ , NSO ₂ R ⁴ , provided that when Y is NH, NR ⁴ , NCOR ^4, or NSO ₂ R ⁴ , and (a) R ² contains a nitrogen-containing saturated heterocycle which is not substituted on the imine nitrogen atom by a hydrogen atom, a methyl group, an ethyl group, a propyl group or an isopropyl group, or b) in the group XNHR ⁴ or XNR ⁴ R ⁴ , optionally present in the substituent R ² , does not represent R ⁴ and / or R ⁴ C 1. ₄ alkyl group, and at the same time that B is COOH, SO ₃ H, PO ₃ H group or a tetrazolyl group _2, and R ¹ and R ² are independently C 5-6-heteroaryl, or phenyl, where these are independently unsubstituted , once substituted with C1-6-alkyl, C1-4-perfluoroalkyl, O-C1-6-alkyl, O-C1-4-perfluoroalkyl, COOH, COO-C1-4-alkyl, CO-C] , 6-alkyl, CONH2, CONHR ^4, NO 2, NH _2, NHCOR ^4, NHSO ₂ R group, or ⁴ by one or two halogen atoms from the group of F, Cl, Br and I, and the following compounds are excluded: [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -acetic acid methyl ester, 5 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester, methyl ester 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butanoic acid, 5 - [[1- (4-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] methyl ester 6 - [[1- (4-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 5 - [[1- (4-aminophenyl) -2- phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid 5 - [[1- [4 - [[(4-chlorophenyl) sulfonyl] amino] phenyl] -2-phenyl-1H-benzimidazole-6- methyl ester yl] oxy] pentanoic acid, 5 - [[1- [4 - [(acetyl) amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, 5 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid, 6 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 5 - [[1- (3-aminophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester 5 - [[1- [3 - [[(4-c) methyl ester] 5-chlorophenyl) sulfonyl] amino] -phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester 5 - [[1- [3 - [(acetyl) amino] phenyl] -2-phenyl- H-benzimidazol-6-yl] oxy] pentanoic acid. Benzimidazoles according to claim 1, characterized in that: R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-2 heteroatoms selected from the group comprising nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH 2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO 2, XNHR ⁴ , XNR ⁴ R ⁴ or R ⁴ , wherein the two substituents on R ¹ are ortho-to each other may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl. Benzimidazoles according to claim 1 or 2, characterized in that: R ² is a mono- or bicyclic C ₆ .i ₀ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-2 heteroatoms selected from the group consisting of N, S or O, wherein said aryl or heteroaryl the group may be independently substituted with up to three of the following substituents: fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCOOH, XCOOR ⁴ , XCONH ₂ , XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ⁴ ', NO ₂ , XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ , XN (SO2R ⁴ ) SO ² R ⁴ , XNR ⁴ SO ² R ⁴ , or R ⁴ , wherein the two substituents on R ² , when in ortho position to each other, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propan-1 , 3-diyl or butane-1,4-diyl. Benzimidazoles according to any one of claims 1 to 3, characterized in that: R ³ is one or two substituents, which independently of one another may be: hydrogen, fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO2NH ₂ , SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO ₂ , group XNH ₂ group, XNHR ⁴ group, XNR ⁴ R ⁴ group, X NHS ₂ R ⁴ group, XNR ⁴ SO 2 R ^4, XN (SO 2 R ⁴⁾ SO ₂ R ⁴ group, XNHCOR ⁴ group XNHCOOR ⁴ group, XNHCONHR ^4, or a group R ^4, where two substituents R ^3, where they are in the ortho position, can be linked so that they together form methanediylbisoxy, ethane-l, 2-diylbisoxy, propane-1,3-diyl, butane-1,4 -diyl group. Benzimidazoles according to one of Claims 1 to 4, characterized in that R ⁴ and R ⁴ independently of one another are CF ₃ , C ₂ F ₅ , C _1-4 -alkyl, C ₂ . ₄ -alkenyl, C _{2nd 4-} alkynyl, C ₃ . ₆ -cycloalkyl, (Cl. ₃ alkyl-C _{3. 6} cycloalkyl), phenyl or 5-6-membered heteroaryl with 1-2 N, S or O, wherein the phenyl and heteroaryl groups can be substituted with one or two substituents selected from the group consisting of fluorine, chlorine, bromine, CH ₃ , C ₂ H ₅ , OCH ₃ , OC ₂ H ₅ , CF ₃ or C ₂ F _5i, and further in the 5-membered cycloalkyl ring, one member of the ring may be nitrogen or oxygen, and in the 6-membered cycloalkyl ring, one or two members of the ring may be nitrogen and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted with C _1-3 -alkyl or Ci. _3- alkanoyl. Benzimidazoles according to any one of claims 1 to 5, characterized in that: R ⁵ and R ⁵ independently of one another are Cl. ₆ -alkyl, wherein the carbon atom can be exchanged for O, NH, N-C. _3- alkyl or N-C _1-3 -alkanoyl, _C3 .7 cycloalkyl-Co_ ₃ -alkyl, wherein the five-membered cycloalkyl ring may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members N and / or O, wherein the nitrogen the ring may be optionally substituted with C 1-6. _{A 3-} alkyl group or a C _1-3 -alkanoyl group, wherein said C _1-6 -alkyl moiety may be substituted by one of the aforementioned cycloalkyl or a 5-6-membered heteroaromatic having 1-2 heteroatoms selected from nitrogen, sulfur or oxygen wherein all of the aforementioned alkyl and cycloalkyl groups may be substituted with up to two substituents selected from the group consisting of CF ₃ , OH, O-C 1. _3- alkyl, and the aforementioned heteroaryl groups may be substituted by one or two substituents selected from the group consisting of fluorine atom, chlorine atom, CF ₃ group, CH ₃ group, C ₂ H ₅ group, OCH ₃ group, OC ₂ group H ₅ , or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7 membered heterocycle which may contain an additional oxygen, nitrogen or sulfur atom and may be substituted by C 1-6. _4- alkyl, C _1-4 -alkoxy-Co. _2- alkyl, C 1-4 -alkoxycarbonyl, aminocarbonyl or phenyl. Benzimidazoles according to any one of claims 1 to 6, characterized in that A is C 1. ₁₀ -alkanediyl, C _{2nd 10} -alkéndiylová group, a _{C2-_io} alkynediyl group, a group (C ₀ _5-alkanediyl-C ₃ _7-cycloalkanediyl-Co-5 alkanediyl), wherein the five-membered cycloalkyl ring may be one member of the ring nitrogen or oxygen atom or a six-membered, and the 7-membered cycloalkyl ring may be one or two ring members nitrogen and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted with a C _1-3 -alkyl or a C _1-3 -alkanoyl group, wherein in the above-mentioned aliphatic chains one or two carbon atoms may be replaced by oxygen, NH, NC]. _3- alkyl or N-C 1 -alkanoyl. Benzimidazoles according to any one of claims 1 to 7, characterized in that: B is COOH, COOR ⁵ , CONH ₂ , CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ or tetrazolyl, each of which is bound to a carbon atom in Group A. Benzimidazoles according to any one of claims 1 to 8, characterized in that X is a bond or a methylene group. 10. Benzimidazoles according to any one of claims 1 to 9, characterized in that Y is an oxygen atom. Benzimidazoles according to any one of claims 1 to 10, which is [(1,2-diphenyl-1H-benzimidazol-6-yl) -oxy] acetic acid isopropyl ester, 3 - [(1,2-diphenyl-1) methyl ester. H-Benzimidazol-6-yl) -oxy] propanoic acid, 2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) -oxy] propanoic acid methyl ester, 4 - [(1,2-Diphenyl) isopropyl ester -1H-benzimidazol-6-yl) oxy] butanoic acid, 5 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid isopropyl ester, 6 - [(1,2-diphenyl- 1H-benzimidazol-6-yl) oxy] hexanoic acid, 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester, 6 - [(l, 2-diphenyl-lH-benzimidazol-6-yl) oxy] hexanamide, N-methoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N - (phenylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazole-6- yl) oxy] hexanamide, 7 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide methyl ester, N-hydroxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide yl) -oxy] heptanoic acid, 6 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[2-phenyl-1- [ 3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy isopropyl ester Hexanoic acid, 6 - [[1- (3-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (3-Cyanophenyl) -2-phenyl] isopropyl ester 6 - [[1- (3-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1-methyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (4-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] - (4-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester oxyjhexánovej. 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-isopropyl] isopropyl ester benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (4-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (4-isopropyl) -isopropyl ester] - chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[1- (4-methylphenyl) -2-phenyl-1H-methyl] methyl ester 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - ((1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester) 6 - [[1- (3,5-Dimethyl-phenyl) -2-phenyl-1H-benzimidazol-6-yl] -ethyl] -hexanoic acid methyl ester 3,4-dimethyl-phenyl) -2-phenyl-1H-benzimidazol-6-yl] 6 - ((1- (3,5-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester) 6 - [(1- (3-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl 6 - [[1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazole] methyl ester 6-yl] oxy] hexanoic acid 6 - [[1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - ((1- (3,4- (methylenedioxy) phenyl) -2-phenyl-1H-benzimidazole) 6-yl] oxy] hexanoic acid, 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[2- 6 - ([2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-) phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, isopropyl ester benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6- 6 - ([1-phenyl-2- [3- (trifluoromethyl) -isopropyl ester] [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoate ) phenyl] -lH-benzimidazol-6-yl] oxy] hexanoic acid j, 6 - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - ([2- (3-chlorophenyl) -1-phenyl- 6 - [[2- (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2- (4-chlorophenyl) -1-phenyl] -1H-benzimidazol-6-yl] oxy] hexanoate, methyl ester 6 - [[2- (4-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester hexanoic acid, 6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[1-phenyl-2- (4-pyridyl) - 6 - ((1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid, 6 - ((1,2-isopropyl ester) -1H-benzimidazol-6-yl] oxy] hexanoate diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid 6 - [[l, 2-diphenyl-5 - [[[(4-trifluoromethyl) phenyl] sulfonyl] amino] -lH-benzimidazole-66 - [[5 - [[[4- (acetylamino) phenyl] sulfonyl] amino 6-Acidyl-1,2-diphenyl-1H-benzimidazol-6 - [[5 - [[bis (3-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl]] - isopropyl ester 6 - [[5 - [[(4-chlorophenyl) sulfonyl] - [[5 - [[(4-bromophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6-A [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-isopropyl ester] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid Benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1,2-Diphenyl-5 - [[(3-methylphenyl) -sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, Isopropyl ester 6 - [[1,2-diphenyl-5 - [[(4-methylphenyl) -sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1,2-diphenyl- 5 - [[(4-methoxyphenyl) -sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexane, isopropyl ester-yl] oxy] hexane, isopropyl ester-yl] oxy] hexane, isopropyl ester xy] hexane, 6 - [[1,2-Diphenyl-5 - [(propylsulfonyl) amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester, 6 - [[5 - [(Benzylsulfonyl) amino] -1-isopropyl ester 2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 2- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] acetic acid methyl ester, methyl ester 3- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) -oxy] ethoxy] propanoic acid, 6 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazole] ethyl ester, 6-yl] oxy] hexanoic acid, 6 - [[4-acetyl-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- 6 [[2-phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazol-5-yl] (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester oxy] hexanoic acid, 6 - [[2-phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[2-phenyl-1 - ( 3-thienyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid, 6 - [[2-phenyl-1- (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methylest 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butanoic acid, N- (phenylmethoxy) -6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) - 1H-benzimidazol-6-yl] oxy] hexanamide, N, N-dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N-isopropyl-6- [ (1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, 6 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] -1-pyrrolidin-1-yl-hexan-1-one, 5 - [[5 - [[(4-chlorophenyl) methyl ester] sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methylphenyl) methyl ester 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-methyl ester 6 - [[4- (acetyloxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[4-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[4-hydroxy-1- (4-methylphenyl) -2- phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[7-methyl-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methyl ester 6 - [[2-phenyl-1- (3-pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid, 6 - [[2-phenyl-1- (3-pyridyl) -1H-] methyl ester Benzimidazol-6-yl] oxy] hexanoic acid, 6- 6 - [[2- (4-Fluorophenyl) -1-phenyl-1H-benzimidazol-6-yl] - [[2-phenyl-1- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester yl] oxy] hexanoic acid 6 - [[2- (4-methoxyphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[2- (4-bromophenyl) -1] methyl ester 6 - [[2- [4- (trifluoromethyl) phenyl] -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl ester, phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl ester 6 - [[1-phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1-phenyl-2- (benzothien-2-yl) -1H] 6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isobutyric acid, 6 - [[5-hydroxy-1- (4-methylphenyl) -2-benzimidazol-6-yl] oxy] hexanoic acid, 6- [ 6 - [[5-Methoxy-1- (4-methylphenyl) -2-phenyl] [5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6H - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 1H-benzimidazol-6-yl] oxy] hexanoic acid, methyl ester 6 - [[5-methoxy- 1- (4-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (3,4-methyl) ester 6-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoate, 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -2- (4-fluorophenyl) -1- 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] -hexanoic acid methyl ester -methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 4 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-methyl ester benzimidazol-6-yljoxy] butanoic acid, 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, methyl ester 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid 6 - [[5 - [[(4- (trifluoromethyl) methyl) ester] phenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] methyl ester meth Ylamino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yljoxy] hexanoic acid, 6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6] methyl ester 6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (3- Fluorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methyl ester 6 - [[1-phenyl-2- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, N - (cyclopropylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazole- 6-yl) oxy] hexanamide, N-isobutoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N - (cyclopropylmethoxy) -6- [2-phenyl-1] - (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide, N-isobutoxy-6- [2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazole 6-yl) oxy] hexanamide, N- (2-methoxyethyl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N- (3-methoxypropyl) -6- [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -hexanamide, N-isobutyl-6 - [(1,2-diphenyl- H-benzimidazol-6-yl) oxy] hexanamide, 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-morpholin-1-yl-hexan-1-one, N, N -di- (2-methoxyethyl) -6- [ (1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N-isopentyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N - (pyrid-2-yl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide, N- (pyrid-3-yl) -6 - [(1,2-diphenyl- 1H-benzimidazol-6-yl) oxy] hexanamide, N-isopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N, N-dimethyl- 6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N, N, N-diethyl-6 - [[1- (3,4-dimethylphenyl) -2] N-isobutyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N-cyclopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N-cyclobutyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, N-tert-butyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide, (R) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimide] idazol-6-yl] oxy] -1- (2-methoxymethyl) pyrrolidin-1-yl-hexan-1-one, N - (3-imidazol-1-ylpropyl) -6 - [[1- (3,4) N-(2-pyrid-2-ylethyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl] -dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide; 1H-benzimidazol-6-yl] oxy] hexanamide, N- (3-methoxypropyl) -6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] heptanamide, 6 - [[1- (4-methylphenyl) -2- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, 6 - [[1- (4-methylphenyl) -2] methyl ester - (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid, 6 - [[1- (4-methylphenyl) -2- (2-thienyl) -1H-benzimidazol-6-yl] methyl ester 6-Benzyl-6-yl-6-benzimidazol-6-yl-6-methyl-6-methyl-6-methyl [1- (4-methylphenyl) -1- (3-thienyl) -1-oxo-hexanoic acid methyl ester - (4-methylphenyl) -1H-benzimidazol-6-yl] oxyjhexanoic acid, 6 - [[1- (4-methylphenyl) -2- (2-furyl) -1H-benzimidazol-6-yl] oxymethyl ester Hexanoic acid, 6 - [[1- (4-methylphenyl) -2- (3-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, m 6 - [[1- (4-methylphenyl) -2- (5-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid ethyl ester, 6 - [[1- (4-methylphenyl) methyl ester 1- [2- (3-Methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexane. A compound according to any one of claims 1 to 11 for use in the treatment, prophylaxis or diangostics. A compound according to any one of claims 1 to 11 for use in the treatment or prevention of diseases associated with microglia activation selected from dementia caused by AIDS, amyotrophic lateral sclerosis, Creuzfeld-Jacob disease, Down syndrome, Lewy body diffusion disease, Huntington's chorea, leukoencephalopathy, multiple sclerosis, neuronal dysfunction and neuronal degeneration, Parkinson's disease, Pick's disease, Alzheimer's disease, stroke, temporal epilepsy and tumors. The use of a compound according to any one of claims 1 to 11 for the manufacture of a medicament for the treatment or prevention of diseases associated with microglia activation selected from dementia caused by AIDS, amyotrophic lateral sclerosis, Creuzfeld-Jacob disease, Down syndrome, Lewy body diffusion disease Huntington's chorea, leukoencephalopathy, multiple sclerosis, neuronal dysfunction and neuronal degeneration, Parkinson's disease, Pick's disease, Alzheimer's disease, stroke, temporal epilepsy and tumors. A pharmaceutical composition comprising one or more compounds according to any one of claims 1 to 11 and one or more carriers. 16. Benzimidazoles of formula (II) (II), wherein: R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group consisting of N, S or O, where the specified aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH 2, C (NR) ⁴ ) NHR ⁴ , C (NR ⁴ ) NR ⁴ R ⁴ , XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC ( NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO ₂ NH ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ⁴ , NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ^4, XN (SO 2 R ⁴⁾ (SO 2 R ⁴⁾ SO 2 R ⁴ XNR group ^4, group ⁴ XNHCOR, XNHCOOR group ^4, group XNHCONHR ^4, tetrahydro-2,5-dioxo-pyrrol-l-yl, 2,5 dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dio xisoisoindol-1-yl or R ⁴ , wherein the two substituents on R ¹ , when in the ortho-position to each other, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3 -diyl or butane-1,4-diyl, R ² is a mono- or bicyclic C ₆ .i ₀ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group consisting of N, S or O, wherein said aryl or heteroaryl the group may be independently substituted with up to three of the following substituents: fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH 2, C (NR) ⁴ ) NHR ⁴ , C (NR ⁴ ) NR ⁴ R ⁴ , XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC ( NOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴ ', XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO ₂ NH ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ⁴ , NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ , XN (SO2R ⁴ XSO2R ⁴ ), XNR ⁴ SO2R ⁴ , XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxopyrol-1-yl, 2,5-dihydro-2 5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxo isoindol-l-yl or a group R ^4, where two substituents on R ^2, where they are in the ortho position, can be linked so that they together form methanediylbisoxy, ethane-l, 2-diylbisoxy, propane-1,3 -diyl or butane-1,4-diyl, R ³ is one or two substituents, which independently of one another may be: hydrogen, fluorine, chlorine, bromine, iodine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR) ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH ₂ , XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ^4, NO2, XNH2, group XNHR ⁴ group, XNR ⁴ R ^4, a group XNHSO2R ⁴ group, XNR ⁴ SO 2 R ⁴ ', XN (SO 2 R ⁴⁾ (SO ₂ R ^4'), the group XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxopyrol-1-yl, 2,5-dihydro-2,5-dioxo-pyrrol-1-yl, A 2,7-dihydro-2,7-dioxoisoindol-1-yl group or an R ⁴ group, wherein the two R ³ substituents, when in ortho position to each other, may be joined together to form a methanediylbisoxy group, ethane-1, 2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl, R ⁴ and R ^4, independently of one another are C _M -perfluóralkylová group, a C ₆ -alkyl, C _{2nd 6} -alkenyl, C _{2nd 6-} alkynyl, C ₃ . ₇ -cycloalkyl, (C ₃ -alkyl-C _{3. 7} cycloalkyl), C ₃ -C ₆ -alkyl _io-aryl, C ₃ -alkylsubstituovaná 5-10-membered heteroaryl with 1-4 nitrogen atoms, sulfur or oxygen, _C-6 .io aryl or 5-10-membered heteroaryl with 1-4 N, s or O, wherein the _C6-IO aryl and-heteroaryl groups may be substituted by one or two of the group, containing fluorine, chlorine, bromine, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ or C ₂ F ₅ , or may also be fused methanediylbisoxy or ethane-1,2-diylbisoxy wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen and the six-membered or seven-membered cycloalkyl ring may be one or two ring members of the nitrogen and / or oxygen atom; the ring nitrogen atoms may be optionally substituted with a C _1-3 -alkyl group or a C _1-3 -alkanoyl group, R ⁵ and R ^5, independently of one another are H, C ₆ -alkyl, C _{2nd 6-} alkenyl or C ₂ . _6- alkynyl, wherein the carbon atom can be exchanged for oxygen, sulfur, SO, SO ₂ , NH, N-C 1. _3- alkyl or N-C _1-3 -alkanoyl, C ₃ . ₇ -cycloalkyl-C ₀ . _{A 3-} alkyl group wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen and one of the six-membered seven-membered cycloalkyl ring may be nitrogen and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted with C _1-3 -alkyl or C 1 -alkyl. _3- alkanoyl, A C 6-10 -aryl group or a 5-10-membered heteroaryl group having 1-4 heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, wherein said alkyl, alkenyl and alkynyl chains may be substituted once from said cycloalkyl, aryl or heteroaryl groups wherein all of the aforementioned alkyl and cycloalkyl groups may be substituted with up to two substituents selected from the group consisting of CF ₃ , C ₂ F ₅ , OH, O-C 1. _3- alkyl, NH ₂ groups, NH-C ₁ groups. _3-alkyl, NH-C _{i. 3-} alkanoyl, N (C _1-3 -alkyl) ₂ , N (C _1-3 -alkyl) (C _1-3 -alkanoyl), COOH, CONH ₂ , COO-C _1-3 -alkyl, and all the aforementioned aryl and heteroaryl groups may be substituted by one or two substituents selected from the group consisting of fluorine, chlorine, bromine, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ and C ₂ F ₅ groups, or may also carry a fused methanediylbisoxy or ethane-1,2-diyl-bisoxy group, or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7-membered heterocycle which may contain an additional oxygen atom , nitrogen or sulfur, and may be substituted with a C _1-4 -alkyl group, C 1-4 -alkoxy-C ₀ . _2- alkyl, C _1-4 -alkoxycarbonyl, aminocarbonyl or phenyl, A is C-io-alkanediyl, C ₂ .i ₀ -alkéndiylová group, a C ₂ .i ₀ -alkíndiylová group, a group _(a C _5-alkanediyl-C _{3. 7-C 0} -cycloalkanediyl _5-alkanediyl) group, ₍₀ C, 5-C-alkándiylarylén ₀ .5 alkanediyl) group, (C _{0th 5} -alkanediyl-heteroarylene-Co-5 alkanediyl), wherein the aryl and heteroaryl groups can be substituted by one or two substituents from the group fluoro , chlorine, bromine, methyl, ethyl, NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ , wherein in the five-membered cycloalkyl ring, one of the ring members may be nitrogen or the oxygen atom and the six or seven membered cycloalkyl ring may be one or two ring members nitrogen and / or oxygen, the ring nitrogen atoms optionally being substituted by a C _1-3 -alkyl or a C _1-3 -alkanoyl group, in the aforementioned aliphatic chains coch one or two carbon atoms may be exchanged for O, NH, NR ⁴ group, NCOR ⁴ or an NSO2R ^4, and the alkyl and cycloalkyl groups can be substituted with up to two substituents from the group consisting of F, Cl, OH , OR ⁴ , OCOR ⁴ , = O, NH 2, NR ⁴ R ⁴ , NHCOR ⁴ , NHCOOR ⁴ , NHCONHR ⁴ , NHSO ₂ R ⁴ , SH and SR ⁴ , B is hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COR ⁵ , C (NOH) R ⁵ , C (NOR ⁵ ) R ⁵ , C (NO (COR ⁵ )) R ⁵ , COOH, COOR ⁵ , CONH2, CONHNH2, CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ , SO 3 H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO2NR ⁵ R ⁵ , PO 3 H, PO (OH) (OR ⁵ ), PO (OR ⁵ ) (OR ⁵ ), PO (OH) (NHR ⁵ ), PO (NHR ⁵ ) (NHR ⁵ ) or tetrazolyl, each of which is attached to each carbon atom of A, or a whole group of YAB is N (SO ₂ R ⁴⁾ (SO 2 R ⁴⁾ or the group NHSO 2 R ^4, X is a bond, CH ₂ , (CH ₂ ) ₂ , CH (CH ₃ ), (CH ₂ ) ₃ , CH (CH ₂ CH ₃ ), CH (CH ₃ ) CH ₂ , CH ₂ CH (CH _3), Y is a bond, an oxygen atom, a sulfur atom, an SO group, an SO ₂ group, an NH group, an NR ⁴ group, an NCOR ⁴ group, or an NSO ₂ R ^{4 group} , for use in treating or preventing diseases associated with microglia activation selected from dementia caused by AIDS, amyotrophic lateral sclerosis, Creuzfeld-Jacob disease, Down's syndrome, Lewy body diffusion disease, Huntington's chorea, leukoencephalopathy, multiple sclerosis, neuronal dysfunction and neuronal degeneration, episode disease, Pickinson's disease, Pickinson's disease, Pickinson's disease, Pickinson's disease, and tumors. Use of benzimidazoles of general formula (II) wherein R ¹ is a mono- or bicyclic C ₆ _i ₂ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group consisting of N, S or O, where the specified aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH 2, C (NR) ⁴ ) NHR ⁴ , C (NR ⁴ ) NR ⁴ R ⁴ , XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC ( NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR , a group XSR ^4, group XSOR ^4, group XSO2R ^4, the group SO 2 NH _2, SO ₂ NHR ^4, a group SO 2 NR ⁴ R ^4, NO 2, XNH _2, groups XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ^4, XN (SO ² R ⁴ ) (SO ² R ⁴ ), XNR ⁴ SO ² R ⁴ , XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxopyrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl or R ⁴ , with two substituents on R ¹ when they are ortho to one another -position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl, R ² is a mono- or bicyclic C ₆ _i ₀ -aryl or a mono- or bicyclic 5-10-membered heteroaryl having 1-4 heteroatoms selected from the group consisting of N, S or O, where the specified aryl or heteroaryl group may be independently substituted with up to three of the following substituents: fluorine atom, chlorine atom, bromine atom, iodine atom, C (NH) NH ₂ , C (NH) NHR ⁴ , C (NH) NR ⁴ R ⁴ , C (NR ⁴ ) NH 2, C (NR) ⁴ ) NHR ⁴ , C (NR ⁴ ) NR ⁴ R ⁴ , XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC ( NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ^4, a group XSR ^4, group XSOR ^4, group XSO2R ^4, the group SO 2 NH _2, SO ₂ NHR ^4, a group SO 2 NR ⁴ R ^4, NO 2, XNH _2, groups XNHR ^4, group XNR ⁴ R ^4, a group XNHSO2R ⁴ , XN (SO 2 R ⁴⁾ (SO 2 R ⁴⁾ SO 2 R ⁴ XNR group ^4, group ⁴ XNHCOR, XNHCOOR group ^4, group XNHCONHR ^4, tetrahydro-2,5-dioxopyrrole-l-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl or R ⁴ , the two substituents on R ² being ortho to one another -position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl, R ³ is one or two substituents, which independently of one another may be: hydrogen, fluorine, chlorine, bromine, iodine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR) ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH2, XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH2, SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO2, XNH2, XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ , XNR ⁴ SO2R ⁴ ', XN (SO2R ⁴ ) (SO ₂ R ⁴ '), XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxopyrol-1-yl, 2,5-dihydro-2 5-dioxopyrrol-1-yl, A 2,7-dihydro-2,7-dioxoisoindol-1-yl group or an R ⁴ group, wherein the two R ³ substituents, when in ortho position to each other, may be joined together to form a methanediylbisoxy group, ethane-1, 2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl, R ⁴ and R ⁴ independently of one another are C _1-4 -perfluoroalkyl, C _1-6 -alkyl, C ₂ . ₆ -alkenyl, C _{2nd 6-} alkynyl, C ₃ . ₇ -cycloalkyl, (C. _{3-alkyl-C3. 7} cycloalkyl), C ₃ -C ₆ -alkyl _io-aryl, C ₃ -alkylsubstituovaná 5-10-membered heteroaryl with 1-4 nitrogen atoms , s or O, C .i _{0 6} -aryl or 5-10-membered heteroaryl with 1-4 N, s or O, wherein the _C6-.io aryl and the heteroaryl groups may be substituted by one or two of a fluorine atom, a chlorine atom, a bromine atom, a CH ₃ group, a C ₂ H ₅ group, a NO ₂ group, an OCH ₃ group, an OC ₂ H ₅ group, a CF ₃ group or a C ₂ F ₅ group; carry a fused methanediylbisoxy or ethane-1,2-diylbisoxy group, wherein in the five-membered cycloalkyl ring, one of the ring members may be nitrogen or oxygen and in the six or seven-membered cycloalkyl ring may be one or two ring members, and / or the ring nitrogen atoms may be optionally substituted with a C _1-3 -alkyl group or a C 1-6 -alkyl group. _3- alkanoyl, R ⁵ and R ^5, independently of one another, H, C p ₆ -alkyl, C _{2nd 6-} alkenyl or C ₂ . _6- alkynyl, wherein the carbon atom may be replaced by oxygen, sulfur, SO, SO ₂ , NH, N-C _1-3 -alkyl or N-C _1-3 -alkanoyl, C ₃ . ₇ -cycloalkyl-C ₀ . _{A 3-} alkyl group wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen and one of the six-membered seven-membered cycloalkyl ring may be nitrogen and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted with C _1-3 -alkyl or C 1-6 alkyl; _3- alkanoyl, _Io _C6-aryl or a 5-10-membered heteroaryl with 1-4 heteroatoms from the group N, S and O, wherein the said alkyl, alkenyl and alkynyl may be substituted one of said cycloalkyl, aryl or heteroaryl groups, wherein all of the aforementioned alkyl and cycloalkyl groups may be substituted with up to two substituents selected from the group consisting of CF ₃ , C ₂ F ₅ , OH, O-C 1. _3- alkyl, NH ₂ groups, NH-C ₁ groups. _3-alkyl, NH-C ₃ -alkanoyl, N (C _{b3-alkyl) 2,} N (C ₃ alkyl) (C ₃ alkanoyl), COOH, CONH _2, COO-C ₃ - alkyl, and all of the aforementioned aryl and heteroaryl groups may be substituted by one or two substituents selected from the group consisting of fluorine atom, chlorine atom, bromine atom, CH ₃ group, C ₂ H ₅ group, NO ₂ group, OCH ₃ group , OC ₂ H ₅ , CF ₃ and C ₂ F ₅ , or may also carry fused methanediylbisoxy or ethane-1,2-diyl-bisoxy, or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7-membered heterocycle, which may contain an additional oxygen, nitrogen or sulfur atom and may be substituted by C 1-6. _4- alkyl, C 1-6 alkyl; _4- Alkoxy-C ₀ . _{A 2-} alkyl group, a C _1-4 -alkoxycarbonyl group, an aminocarbonyl group or a phenyl group, A is a Ci.io-alkanediyl, C _2nd | ₀ -alkéndiylová group, a C ₂ _i ₀ -alkíndiylová group, a group (C ₀ _5-alkanediyl-C _{3. 7} -cycloalkanediyl-Co_ ₅ -alkanediyl), (CO-5-alkándiylarylén _the C-.5-alkanediyl), skupma _(Co _5-alkanediyl-heteroarylene-Co-5 alkanediyl), wherein the aryl and heteroaryl groups can be substituted by one or two substituents from the group of F, Cl, Br, methyl, ethyl, a group NO _2, OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ , wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen, and the six-membered or seven-membered cycloalkyl ring may be one or two ring members and / or oxygen, wherein the ring nitrogen atoms may be optionally substituted by a C _1-3 -alkyl group or a C _1-3 -alkanoyl group, wherein in the above-mentioned aliphatic chains one or two carbon atoms may be AMEN for O, NH, NR ⁴ group, NCOR ⁴ or an NSO2R ^4, and the alkyl and cycloalkyl groups can be substituted with up to two substituents from the group consisting of F, OH, OR ^4, OCOR ⁴ , atom = 0, NH 2, NR ⁴ R ⁴ , NHCOR ⁴ , NHCOOR ⁴ , NHCONHR ⁴ , NHSO ₂ R ⁴ , SH and SR ⁴ , B is hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COR ⁵ , C (NOH) R ⁵ , C (NOR ⁵ ) R ⁵ , C (NO (COR ⁵ )) R ⁵ , COOH, COOR ⁵ , CONH2, CONHNH2, CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ , SO 3 H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO2NR ⁵ R ⁵ , PO 3 H, PO (OH) (OR ⁵ ), PO (OR ⁵ ) (OR ⁵ '), PO (OH) (NHR ⁵ ), PO (NHR ⁵ ) (NHR ⁵ ) or tetrazolyl, each of which is attached to each carbon atom of A, or a whole group of YAB is N (SO ₂ R ⁴⁾ (SO 2 R ⁴⁾ or the group NHSO 2 R ^4, X is a bond, CH ₂ , (CH ₂ ) ₂ , CH (CH ₃ ), (CH ₂ ) ₃ , CH (CH ₂ CH ₃ ), CH (CH ₃ ) CH ₂ , CH ₂ CH (CH _3), Y is a bond, oxygen, sulfur, SO, SO ₂ , NH, NR ⁴ , NCOR ^4, or NSO ₂ R ⁴ , for the manufacture of a medicament for the treatment or prevention of diseases associated with the activation of microglia, selected from dementia caused by AIDS, amyotrophic lateral sclerosis, Creuzfeld-Jacob disease, Down's syndrome, Lewy body diffusion disease, Huntington's chorea, leukoencephalopathy, multiple sclerosis, neuronal dysfunction and neuronal degeneration, Pickinson's disease, Parkinson's disease, Sickness Disease, Parkinson's disease, epilepsy and tumors. Use according to claims 16 or 17, wherein in formula (II) R ¹ is a monocyclic or bicyclic aryl group or a monocyclic or bicyclic 5-10-membered heteroaryl group with 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, wherein said aryl or heteroaryl group may be independently substituted with up to with the following three substituents: fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH 2, XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO 2, XNHR ⁴ , XNR ⁴ R ^4, or R ⁴ , wherein the two substituents on R ¹ are ortho to each other position, may be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl. Use according to any one of claims 16 to 18, wherein in formula (II) R ² is a mono- or bicyclic aryl or mono- or bicyclic 5-10-membered heteroaryl having 1-2 heteroatoms selected from the group consisting of N, S or O, wherein said aryl or heteroaryl group may be independently substituted with up to with the following three substituents: fluorine atom, chlorine atom, bromine atom, XOH group, XOR ⁴ group, XOCOR ⁴ group, XOCONHR ⁴ group, XOCOOR ⁴ group, XCOR ⁴ group, XC (NOH) R ⁴ group, XC (NOR ⁴ ) R ⁴ group, XC (NO (COR ⁴ )) R ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONH ₂ , XCONR ⁴ R ⁴ , XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR, XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , SO2NR ⁴ R ⁴ , NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ , XNHSO2R ⁴ , XN (SO2R ⁴ ) (sO 2 R ⁴⁾ group, XNR ⁴ sO 2 R ^4, a group XNHCOR ^4, group XNHCOOR ^4, group XNHCONHR ^4, or a group R ^4, where two substituents on R ^2, where they are in the ortho position, can be linked such that, together they form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane-1,4-diyl. Use according to any one of claims 16 to 19, wherein in formula (II) R ³ is one or two substituents independently of one another: hydrogen, fluorine, chlorine, bromine, XOH, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XC (NOH) R ⁴ , XC (NOR ⁴ ) R ⁴ , XC (NO (COR ⁴ )) R ⁴ , XCN, XSR ⁴ , XSOR ⁴ , XSO ₂ R ⁴ , SO2NH ₂ , SO2NHR ⁴ , SO2NR ⁴ R ⁴ , NO ₂ , XNH ₂ group, XNHR ⁴ group, XNR ⁴ R ⁴ ', the group X NHS ₂ R ⁴ group, XNR ⁴ SO 2 R ^4', XN (SO 2 R ⁴⁾ (SO ₂ R ⁴ '), the group XNHCOR ⁴ group XNHCOOR ⁴ group, XNHCONHR ⁴ or R ⁴ , wherein the two R ³ substituents, when in the ortho position, can be joined together to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl or butane- 1,4-diyl. Use according to any one of claims 16 to 20, wherein in the general formula (II) R ⁴ and R ^4, independently of one another are CF _3, C ₂ F _5, C _{(. 4} alkyl, C ^ -alkenyl, _{C2. 4} -alkynyl, C _{3. 6} -cycloalkyl, (C |. ₃ -alkyl-C _{3. 6} cycloalkyl), C _{i. 3} alkylaryl, C. -alkylheteroarylová ₃ group, a monocyclic aryl or 5-6-membered heteroaryl with 1-2 N, s or oxygen, wherein the aryl and heteroaryl groups may be substituted by one or two substituents from the group consisting of fluorine atom, chlorine atom, bromine atom, CH ₃ group, C ₂ H ₅ group, NO ₂ group, OCH ₃ group, OC ₂ group H ₅ , CF ₃ or C ₂ F ₅ , or may also carry fused methanediylbisoxy or ethane-1,2-diylbisoxy wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen, and one of the six-membered cycloalkyl ring may be one or two ring members at the nitrogen atom and / or the oxygen atom, wherein the ring nitrogen atoms may be optionally substituted by a C _1-3 -alkyl group or a C _1-3 -alkanoyl group. Use according to any one of claims 16 to 21, wherein in formula (II) R ⁵ and R ⁵ independently of one another are C 1-6. ₆ -alkyl, wherein one carbon atom can be exchanged for O, NH, NC _{(. 3-alkyl} or N-C ₃ alkanoyl, C ₃ .7 cycloalkyl Co_3-alkyl, wherein the five membered cycloalkyl may be one member of the ring is N or O and, six or seven membered cycloalkyl ring may be one or two ring members N and / or O, wherein ring nitrogen atoms can be optionally substituted with Ci. ₃ -alkyl or C _{i. A 3-} alkanoyl group, wherein said C 1-6 -alkyl moiety may be substituted by one of said cycloalkyl groups or also by one of 5-6-membered heteroaromates having 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, wherein all said alkyl and cycloalkyl groups may be substituted by up to two substituents selected from the group consisting of from CF _3, OH, OC _{t. 3} alkyl, and the previously mentioned heteroaryl groups can be substituted by one or two substituents from the group consisting of fluoro, chloro, CF _3, CH _3, group C ₂ H ₅ , OCH ₃ and OC ₂ H ₅ , or R ⁵ and R ⁵ together with the nitrogen atom form a 5-7 membered heterocycle which may contain an additional oxygen, nitrogen or sulfur atom and may be substituted by C 1-6. ₄ -alkyl, C ₄ -alkoxy Co_ ₂ -alkyl, C. ₄ -alkoxycarbonyl, aminocarbonyl or phenyl. Use according to any one of claims 16 to 22, wherein in formula (II) A is a Ci.io-alkanediyl, C ₂ _i ₀ -alkéndiylová group, a C ₂ .i ₀ -alkíndiylová group, a group (C0.5-alkanediyl-C ₃ .7-cycloalkanediyl-C ₀ _5-alkanediyl) group, or ( C0-5-alkanediyl-heteroarylene-C0-5-alkanediyl), wherein the optionally present heteroaryl group may be substituted by one or two substituents from the group fluorine atom, chlorine atom, bromine atom, CH ₃ group, C ₂ H 5 group, NO ₂ group, OCH ₃ , OC ₂ H ₅ , CF _3, and C ₂ F ₅ , wherein one of the five-membered cycloalkyl ring may be nitrogen or oxygen and the six-membered or seven-membered cycloalkyl ring may be one or two ring members and or oxygen, wherein the ring nitrogen atoms may be optionally substituted by C 1. C ₃ alkyl; ₃ -alkanoyl, wherein in the aliphatic chain one or two carbon atoms can be replaced by an oxygen atom, an NH group, an N-C1 group. _3- alkyl, N-C _1-3 -alkanoyl or NSO ₂ C ₁ . ₃ alkyl, and the alkyl or cycloalkyl moieties may be substituted with up to two fluorine atoms, or one of the substituents of the group consisting of OH, OC _{i. 3-} alkyl, O-C _1-3 -alkanoyl, = O, NH ₂ , NH-C _1-3 -alkyl, N (C _1-3 -alkyl) ₂ , NHC _1-3 -alkanoyl, N (C) _{first 3} alkyl) (C. ₃ alkanoyl), of NHCOOCi_ ₃ -alkyl, NHCONHCi_ ₃ alkyl, NHSO ₂ C group. _3- alkyl, SH groups and SC groups]. _3- alkyl, Use according to any one of claims 16 to 23, wherein in formula (II) B is hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COOH, COOR ⁵ , CONH ₂ , CONHR ⁵ , CONR ⁵ R ⁵ , CONHOH, CONHOR ⁵ or tetrazolyl each of which is bound to a carbon atom of group A. Use according to any one of claims 16 to 24, wherein in formula (II) X is a bond or a CH ₂ group. Use according to any one of claims 16 to 25, wherein in formula (II) Y is a bond, an oxygen atom, a sulfur atom, an NH group, an NR ⁴ group, an NCOR ⁴ group, or an NSO ₂ R ^{4 group} .