BG65858B1 - 1,2-diaryl benzimidazoles for treating illnesses associated with a microglia activation - Google Patents

Abstract

The invention relates to benzimidazoles of the general formula and to the use of their derivatives for the preparation of medicaments for the treatment and prophylaxis of diseases which are associated with activation of microglia.

Description

Technical field

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

BACKGROUND OF THE INVENTION

Almost all central nervous system degenerative diseases are associated with a single chronic inflammation. An important factor in the manifestation of an inflammation is the activation of mononuclear phagocytic cells, microglia. The latter occurs, for example, in Alzheimer's disease through senile plague, in Kreuzfeld's disease

- Jacobs through a prion protein and ischemic strokes through dead cells. Microglia remain in active form for a longer period of time, during which they produce and release various inflammatory factors, for example reactive oxygen / nitrogen - intermediates, proteases, cytokines, additional factors and neurotoxins. The latter cause neurodysfunction and degeneration again.

Non-steroidal anti-inflammatory drugs (COX11 inhibitors) have not been described to date for possible neuroinflammation therapy (Me Geer, R. L. Roger, Necrology 42, 447 - 449 (1992), Rogers, J., Kirby, L. C., Hempieman, S. R., Berry, D. L. Me Geer, P. L. Kaszniak, A. W., Zalinski, J., Cofield, M., Mansukhani, L., Wilson, P., Kogan, F. Neurology 43, 1609-1611 (1993), Andersen, K.,. Launer, L.J., Ott, A., Hoes, A.W., Breteler, B., B., Hofman, A. Neurology 45, 1441-1445 (1995), Breitner, JCS, Gau, B.A. Welsh, K.A., Plassman, B.L. , McDonald, WM, Helms, MJ, Anthony, JC Neurology 44, 227232 (1994), The Canadian Study of Health and Aging, Neurology 44, 2073-2079 (1994), Cytokin

- Modulatoren (McGeer, PL, McGeer, EG Res. 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 complementary degree inhibitors (Chen., S., Frederickson, RCA, and Brunden, KR, Neurobiol. Aging (1996), McGeer, E.G., and McGeer, P. L, Drugs 55: 739-746 (1998) These substances impede the synthesis or action of individual inflammatory factors, but it may be desirable to have such substances that would prevent the development of an earlier stage of inflammation and this way, to prevent the occurrence or action of multiple factors of influenza deer.

SUMMARY OF THE INVENTION

This existing problem is solved by the creation of benzimidazole derivatives of general formula I, their tautomers or isomers or salts

wherein

R ¹ means one mono- or bicyclic C _612- aryl group or one mono- or bicyclic 5-10-membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of N, S or 0, such as aryl or heteroaryl groups may be substituted by up to three of the following substituents independently of each other:

F, Cl, Br, I,

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, XSO2R ^4, so2nh _2, so ₂ nhr ^4, SO2NR ⁴ R ⁴ ', no2, xnh _2, XNHR ^4, XNR ⁴ R ^4', xnhso2r ^4, XN (SO2R ⁴⁾ so2r ⁴ ', xnr ⁴ so2r ⁴ ',

XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ ,

65858 B1 tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5-dioxopyrrol-1-yl, 1,2-dihydro2,7-dioxyisoindol-1-yl, R ⁴ as two substituents to R ¹ , when positioned in relation to each other in an ortho position, may be so connected to each other that together they form methandylbisoxy, ethane-

1,2-diylbisoxy, propane-1,2-diyl, butane-1,4diyl,

R ² denotes one mono- or bicyclic C ₆₁₀ -aryl group or one mono- or bicyclic 5-10 membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of N, S or O, such as aryl or heteroaryl a group may be independently substituted by up to three of the following substituents:

HON, 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, SO ^, SO2NHR ^4, so ₂ nr ⁴ r ⁴ ', no _2, XNHR ^4, XNR ⁴ R ^4', xnhso2r ^4, XN (SO2R ⁴⁾ so2r ⁴ ', xnr ⁴ so2r ⁴ ', tetrahydro-2,5-dioxypyrrol-1-yl, 2,5dihydro-2,5-dioxypyrrol-1-yl, 2,7-dihydro2,7-dioxyisoindol-1-yl, R ⁴ as the substituents on R ² , when positioned in ortho-position with one another, may be connected to each other so as to form methanediylbisoxy, ethane-1,2diylbisoxy, propane-1,3-diyl, butane-1,4-diyl,

R ³ means one or two substituents which may independently mean:

Hydrogen,

F, C1, Br, I,

ΧΟΗ, 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 ',

NO ₂ , XNH ,, XNHR ⁴ , XNR ⁴ R ⁴ ', xnhso2r ⁴ , XNR ⁴ SO2R 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 , as the two substituents R ³ , when positioned in the ortho position with respect to each other, can be so joined together that they together form methandylbisoxy, ethane-1,2-diylbisoxy, propane-1,3- diyl, butane-1,4-diyl,

R ⁴ and R ⁴ 'independently of one another represent C _m perfluoroalkyl, C ₁₆ alkyl, C ₂ alkenyl, C _{2. b} alkynyl, _{C3 7} cycloalkyl, (C ₁₃ alkyl-C _{3 7} cycloalkyl), C ₁₃ alkyl-C _{6! 0} aryl, _C13 alkyl 5-10-membered heteroaryl with 1-4 N-, S - or O - atoms, _C10 aryl or 5-10 membered heteroaryl with 1-4 N-, S- or O-atoms, the aryl and heteroaryl groups being substituted by one or two substituents of the group consisting of F , C1, Br, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , cf ₃ , c ₂ f ₅ or may have one annealed methandiylbisoxy-, ethane-1,2-diylbisoxy group, and except this in one 5-membered cycloalkyl ring one member of the ring can be one nitrogen one oxygen and in one 6- or 7-membered ene cycloalkyl ring one or two ring members can be N and / or oxygen, the nitrogen of the ring may optionally be substituted with alkyl of 1-3 carbon atoms or alkanoyl of 1 to 3 carbon atoms,

R ⁵ and R ⁵ 'independently represent alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, one carbon atom being substituted by O, S, SO. SO ₂ , NH, NC ₁₃ alkyl or NC ₁₃ alkanoyl,

C _3-7 cycloalkyl - C _0-3 alkyl, wherein in one 5-membered cycloalkyl ring one member of the ring may be one nitrogen or one oxygen, and in one 6- or 7-membered cycloalkyl ring one or two members of the ring may be nitrogen and / or oxygen, the ring nitrogen being optionally substituted by alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms

With _and0 -aryl or 5-10-membered heteroaryl with 1 4 heteroatoms from N, S and O, said alkyl, alkenyl and alkynyl chains can be substituted with one of the already mentioned cycloalkyls, aryls or heteroaryls, each of the foregoing alkyl and

65858 B1 cycloalkyl radicals may be substituted by one to two substituents of CF ₃ , C ₂ F ₅ , OH, Ο C ₁₃ alkyl, NH ₂ , NHC ₁₃ alkyl, NHC, ₃ alkanoyl, N (C ₁₃ alkyl) ₂ , N (C _1-3 alkyl) (C _6-3 alkanoyl), COOH, CONH ₂ , COO C ₁₃ alkyl and all of the above aryl and heteroaryl groups may be substituted and one or two substituents of the group consisting of F, Cl, Br , CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ and may also have one annealed methanediylbisoxy, ethane-

The 1,2-diylbisoxy group, or R ⁵ and R ⁵ 'together with the nitrogen atom form a 5-7 membered heterocycle which may contain another oxygen, nitrogen or sulfur atom and may be substituted by C _1-4 alkyl, C _1-4 alkyl alkoxy-C ₂ alkyl, C ₁ alkoxycarbonyl, aminocarbonyl or phenyl,

A stands for alkanediyl of 1 to 10 carbon atoms, alkenediyl of 2 to 10 carbon atoms, alkinediyl of 2 to 10 carbon atoms, (C _{0 5} alkanediyl-C _{3 7} cycloalkanediyl-C ₀₅ alkanediyl), such as in a 5-membered cycloalkyl ring one ring member may be nitrogen or oxygen and in one 6- or 7-membered cycloalkyl ring one or two of the ring members may be nitrogen and / or oxygen, wherein the nitrogen in the ring may be optionally substituted by alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms in the above aliphatic chains and one or two carbon atoms may be replaced by O, NH, NC ₁₃ alkyl, NC _b3 alkanoyl, and in that the alkyl or cycloalkyl groups can be substituted with up to two substituents selected from = 0, OH, _{OC) 3} alkyl, NH ₂ , NHC ₁₃ alkyl, NHC ₁₃ alkanoyl, N (C ₁₃ alkyl) ₂ , N (C ₃ alkyl) ₂ , N (C ₃ alkyl) (C ₁₃ alkanoyl),

B means

COOH, COOR ⁵ , conh2, conhnh2, CONHR ⁵ , CONR ⁵ R ⁵ ', CONHOH, CONHOR ⁵ , SO3H, are ₂ nh ₂ , are ₂ nhr ⁵ , are 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 ), tetrazolyl, usually bonded to one carbon atoms in group A or the general group YAB N (SO ₂ R ⁴ ) (SO ₂ R ⁴ ) or IBO ^ ⁴ ,

X stands for single bond, SN ₂ , SD, NSC), (CH ₂ ) ₃ , SN

CH (CH ₃ ) CH ,, sn stau,

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

a) the radical R ² contains a nitrogen-containing saturated heterocycle, this heterocycle is not substituted to the imine nitrogen atom by H, methyl, ethyl, propyl or isopropyl, or

b) and optionally available XHNR ⁴ or XNR ⁴ R ⁴ 'in the radical R ² R ⁴ and / or R ⁴ ' do not mean alkyl of 1 to 4 carbon atoms, provided that at the same time B is COOH, SO ₃ H, PO ₃ H ₂ or tetrazolyl and R ¹ and R ² independently of one another denote heteroaryl of 5 to 6 carbon atoms or phenyl, when they are not independently substituted, simply substituted with alkyl of 1 to 6 carbon atoms, perfluoroalkyl having 1 to 4 carbon atoms, OCj 6 alkyl, OCj 4 perfluoroalkyl, COOH, COOCW alkyl, SOMC, CONHR ⁴ , NO2, NH ₂ , NHCOR ⁴ , NHSOjR ⁴ or c 1 or 2 halogen atoms of the group F, Cl , Br, J, and in which locked out following compounds:

[(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 ester, 5 - [[1- (4-nitrophenyl) 2phenyl-1H-benzylimidazol-6-yl] oxy ester ] pentanoic acid, 6 - [[1- (4-nitrophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 5 - [[1- (4-aminophenyl) 2-phenyl- 1H-benzimidazol-6-yl] oxy] pentanoic acid, 5 - [[1- [4 - [[(4-chlorophenyl) sulfonyl] amino] phenyl-2-phenyl-1H-benzimethyl] ester dazol-6-yl] oxy] pentanoic acid, 5 - [[1- [4- (acetyl) amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, methyl ester 5 - [[1- (3-nitrophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid, 6 - [[1- (3-nitrophenyl) -2 methyl ester

65858 B1 phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid, 5 - [[1- (3-aminophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, methyl ester of 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-benzimidazol-6-yl] oxy] pentanoic acid.

Physiologically tolerated salts may be prepared 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, p-sulfonic acid, p-sulfuric acid acid, methanesulfonic acid.

Suitable salts with acid groups are also suitable inorganic or organic bases which are known for the formation of physiologically tolerated salts such as alkyl hydroxides, sodium and potassium hydroxide, alkaline earth hydroxides and such as calcium hydroxide, ammonia, amines, ethanolamines, ethanolamines, ethanolamines N-methylglucamine, Tris- (hydroxymethyl) -methylamine.

A " aryl group " is intended to mean in particular a substituted phenyl group or biphenyl, naphthyl, indane or fluorenyl.

A heteroaryl group is composed of 5-10 atoms in the skeleton and may contain 1 to 4 heteroatoms. Heteroatoms are oxygen (O), nitrogen (N) and sulfur (S). Examples of a monocyclic heteroaryl group are pyrrolyl, thienyl, furanyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, furazanyl, pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl. An example of a bicyclic heteroaryl group satenoimidazolyl, indolyl, isoindolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl, imidazopyridinyl, pyrinyl, quinolyl, isoquinolinyl, phthalazinyl, quinolinolinylninolinolinolinyl When aryl or heteroaryl are part of R ¹ , the coupling to the benzimidazole nitrogen via a carbon atom follows.

The alkyl groups may be straight or branched. They are, for example, metal, ethylene, propyl, isopropyl, η-piston, sec. piston, third. piston, p-pentile, sec. pentile, third. pentyl, neopentyl, n-hexyl, sec. hexyl, heptyl, octyl, nonyl, hexyl.

Perfluorinated alkyls are preferably CF ₃ and C ₂ F _s and alkanoyls preferably formyl, acetyl, propionyl.

The alkenyl groups may be straight or branched. For example, the following radicals could be mentioned: vinyl, 2-propenyl, 1-propenyl, 2-butenyl, 1-butenyl, 1-methyl-1-propenyl, 2-methyl-2-propenyl, 3-methyl-2-propenyl.

The alkynyl groups may be straight or branched. Examples are: ethyl, 1-propyl, 2-propyl, 1-butynyl, 2-butynyl

Cycloalkyl groups are generally understood to mean cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

As a saturated heterocycle or cycloalkyl with 1 or more heteroatoms, for example, the following may be mentioned: piperidine, pyrrolidine, tetrahydrofuran, morpholine, piperazine, hexahydroazepine as well as 2,6dimethylmorpholine, N-phenyl-piperazine, methoxymethylsulfinylphenol the atom may optionally be made available by the available nitrogen in the ring.

For example, alkanes, alkenes and alkynes for A may be mentioned:

Straight or branched chain alkylene with 1-8 carbon atoms such as: metal, ethylene, propylene, butylene, pentylene, etc., 1-methylethylene, 1-ethylethylene, 1-methylpropylene, 2-methylpropylene, 1-metalbutylene, 2-metalbutylene ,

1- ethylbutylene, 2-ethylbutylene, 1-methylpentylene,

2- methylpentene, 3-methylpentylene, etc.

Straight or branched chain alkenylene and alkynylene 2-8 carbon atoms are alkylene groups, respectively, of double and triple bond alkynylene groups in all possible positions and with all possible metal or

65858 B1 ethyl substitution. In these radicals, typically one or two carbon atoms may be replaced by O, NH, NC, _ ₃ alkanoyl, such as the replaced group is separated from Y by at least two carbon atoms.

When two radicals are located on the ortho-site, they can form compounds with a common ring with two adjacent atoms. Compounds in which the nitrogen, oxygen or sulfur atoms are linked by olefin or acetylene unsaturated bonds, or in which more nitrogen, oxygen, sulfur or halogen atoms are linked to the same aliphatic carbon atom, or in which the nitrogen, oxygen or sulfur atoms are attached directly to each other, are excluded, insofar as these bonds are not explicit, are defined in the functional groups or heteroatoms specified in the claims.

Benzimidazoles are preferred in which

R ¹ denotes one mono- or bicyclic aryl group having 6-12 carbon atoms or one mono- or bicyclic 5-10 membered heteroaryl group with 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, such as said aryl or a heteroaryl group may be independently substituted by the following substituents:

F, C1, Br,

HON, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ ,

XCOR ⁴ , XCN, XCOOH, XCOOR ⁴ , XCONIL, XCONR ⁴ R ⁴ ', XCONHR ⁴ , XCONHOH,

XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', R ⁴ , wherein two substituents on R ¹ , when arranged relative to each other in the ortho position, can thus be bonded to each other that together form methandyisisbisoxy, ethane-

1,2-diylbisoxy, propane-1,3-diyl, butane-1,4diyl.

Benzimidazoles are also preferred in which

R ² denotes one mono- or bicyclic group of 6-10 carbon atoms or one mono-or bicyclic heteroaryl group of 5-10 members with 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, such as aryl or heteroaryl a group may be independently substituted by one to three of the following substituents:

F, C1, Br,

HON, 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., XCONHR ⁴ , XCONR ⁴ R ⁴ ', XCONHOH, XCONHOR ⁴ , XCOSR ⁴ ,

XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO.NH ,, SOZNHR ⁴ , SO ₂ NR ⁴ R ⁴ ',

NO ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XN (SO2R ⁴ ) so2r ⁴ ', xnr ⁴ so2r ⁴ ', r ⁴ as two substituents to R ² when positioned relative to each other in the ortho position, may be so interconnected that together they form methandiylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl.

Benzimidazoles of the general Formula I, in which, are also preferred

R ³ means one or two substituents which may independently mean:

Hydrogen, fluorine, chlorine, bromine,

HON, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ ,

XCOR ⁴ , XC (NOH) R ⁴ , XC (NOOR ⁴ ) R ⁴ ', XC (NO (COR ⁴ )) R ⁴

XCN, XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , are ₂ nhr ⁴ , are ₂ nr ⁴ r ⁴ ',

NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ N ⁴ ',

XNHSO ₂ R ⁴ , XNR ⁴ SO ² R ⁴ ', XN (SO ² R ⁴ ) SO ^ ⁴ ',

XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , or R ⁴ , as two of the substituents R ³ , when positioned relative to each other in the ortho position, can thus be coupled to each other to form methadiylbisoxy, ethane-1,2 -diylbisoxy, propane-1,3-diyl, butane-1,4-diyl.

Also preferred are benimidazoles of general formula I, in which

R ⁴ and R ⁴ 'independently of one another are CF ₃ , C ₂ F ₅ , alkyl of 1-4 carbon atoms, alkenyl of 2-4 carbon atoms, alkynyl of 2-4 carbon atoms, cycloalkyl of 3-6 carbon atoms (C ₁₃ alkyl-C _{3. 6} cycloalkyl), phenyl or 5-6-membered heteroaryl with 1-2 nitrogen, sulfur or oxygen atoms, the phenyl and heteroaryl groups can be substituted with one or two substituents from the group consisting from fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy,

65858 Bl

CF ₃ , C ₂ F _? and in addition in one 5-membered cycloalkyl ring one member of the ring may be nitrogen or oxygen and in one 6-membered cycloalkyl ring one or two members of the ring may be nitrogen and / or oxygen, the nitrogen of the ring being optionally may be substituted with alkyl of 1-3 carbon atoms or with alkanoyl of 1-3 carbon atoms.

Benzimidazoles of general formula I are also preferred in which

R ⁵ and R ³ 'independently represent alkyl of 1-6 carbon atoms, one carbon atom may be substituted by NH, NC _{b 3} alkyl, NC ₃ alkanoyl,

C ₃ _ ₇ cycloalkyl-C _{0 3} alkyl, in a 5-membered cycloalkyl ring one ring member may be nitrogen or oxygen, and in a 6- or 7-membered cycloalkyl ring one or two ring members can be N and / or oxygen, the nitrogen of the ring being optionally substituted by alkyl of 1-3 carbon atoms or alkanoyl of 1-3 carbon atoms, said alkyl of the 1-6 carbon atoms being replaced by one already mentioned cycloalkyl or also to be substituted by one 5-6 membered heteroaromatic compound with 1-2 heteroa volumes selected from nitrogen, sulfur or oxygen, wherein the alkyl and cycloalkyl moieties mentioned herein may be substituted by one to two substituents of the group CF ₃ , OH, O C ₁₃ alkyl, and the above heteroaryl groups may be substituted with one to two substituents of fluorine, chlorine, CF ₃ , methyl, ethyl, methoxy, ethoxy and R ⁵ and R ⁵ 'form together with the nitrogen atom a 5-7 membered heterocycle which may contain another oxygen, nitrogen or sulfur atom and may be substituted with alkyl of 1-4 carbon atoms, C _{m alkoxy-C0 2} alkyl, C _1h alkoxy - carbonyl, aminocarbonyl bonyl or phenyl.

Benzimidazoles of the general Formula I are also preferred, wherein

A represents alkanediyl having 1-10 carbon atoms, alkenediyl with 2-10 carbon atoms, alkindiil with 2-10 carbon atoms (C _{o 5} alkanediyl-C _{3 7} cycloalkanediyl-C _{0 5} alkanediyl), with a 5-membered cycloalkyl ring one member of the ring may be nitrogen or one oxygen and in one 6- or 7-membered cycloalkyl ring one or two of the ring members may be nitrogen and / or oxygen, the nitrogen in the ring may optionally be substituted with allyl having 1-3 carbon atoms or with alkanoyl having 1-3 carbon atoms, such as in the above aliphatic chains din or two carbon atoms may be replaced by oxygen, NH, NC _W alkyl, NC _b3 alkanoyl.

Benzimidazoles of general formula I are also preferred, wherein

B stands for COOH, COOR ⁵ , CONH ₂ , CONHR ³ , CONR ⁵ R ³ ', CONHOH, CONHOR ³ or tetrazolyl, usually bonded to one carbon atom of group A.

Particularly preferred is B with meanings

COOR ³ , CONH ,, CONHR ³ , CONR ³ .

Benzimidazoles of the general Formula I are also preferred, wherein

X stands for single bond or methylene.

Benzimidazoles of the general Formula I are also preferred, wherein

Y stands for oxygen.

Preferably R ¹ and R ² independently represent phenyl or 5-6 membered heteroaryls, with 1-2 heteroatoms such as nitrogen, oxygen or sulfur atoms which may be substituted by fluorine, chlorine, bromine, cyano, alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms, methylenedioxy, alkylthio with 1-4 carbon atoms, NO ₂ , CF ₃ , NH ₂ , MH (C ₁₃ alkyl), Ν (Ο _μ3 alkyl) ₂ .

Particularly preferred for R ³ is hydrogen, fluorine, chlorine, OH, alkoxy of 1-4 carbon atoms, alkyl of 1-4 carbon atoms, NO ₂ , NH ₂ , NH-C 1-6 alkanoyl N-C 1-4 phenyl, such as phenyl radical can be substituted by fluorine, chlorine, bromine, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, CF ₃ or acetylamino.

The following benzimidazoles are particularly preferred:

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

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

2 - [(1,2-diphenyl-1H-benz) methyl ester

65858 Blimidazol-6-yl) oxy] propanoic acid

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

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

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

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

6- [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

B1-methoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

T4- (phenylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

L1-hydroxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

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

6 - [[1- (3nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] ester ] -1H-Benimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[2-phenyl-1- [3 (trifluoromethyl) phenyl] 1H-benzimidazol-6yl] hexanoic acid methyl ester of 6 - [[1- (3-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[1- (3cyanophenyl) -2-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- (4-cyanophenyl) -2-phenyl-1H-benzimidazole] 6 - [[1- (4cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (3-yl) oxy] hexanoic acid isopropyl ester Chlorophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1- (4-chlorophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[1- (4-chlorophenyl) 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 of 6 - [[1- (3-methylphenyl) 6 - [[1- (4-methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[1- (4methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazole 6 - [[1- (3,5-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] -6-yl] oxy] hexanoic acid methyl ester] 6 - [[1- (3,5-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[1- (3-methoxyphenyl) 2 methyl] 6 - [[1- (4-methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6- ester-phenyl-1H-pyrimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1- [3,4- (methylenedioxy) phenyl] -2 [[1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester -phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid

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

6 - [[2-Phenyl-1- (3,4,5-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[2-phenyl-1 (3,4,5 - trimethoxyphenyl) -1H-benzimidazol-6yl] oxy] hexanoic acid 6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester

6 - [[1- [4- (H, dimethylamino) phenyl] -2

65858 B1 Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1-phenyl-2- [3 (trifluoromethyl) phenyl] 1 H-benzimidazo-6-yl] oxy] hexanoic acid 6 - [[2- (3-Chlorophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[2- (3-chlorophenyl) -1-phenyl-1H- benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2- (4-cyclopentyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[2- (4chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of nab - [[2- (4-methylphenyl) -1phenyl-1 N - benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2- (4methylphenyl) -1-phenyl-1H-benzimidazol] oxy] hexanoic acid isopropyl ester 6 - [[1-phenyl-2 methyl] - (4-Pyridinyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid 6 - [[5 - [[(4-bromophenyl) sulfonyl] amino-1,2-diphenyl] isopropyl ester - 1H-Benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl methyl ester yl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] isopropyl ester ] oxy] hexanoic acid 6 - [[1,2-diphenyl-5 [[(3-methylphenyl) sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid 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] hexanoic acid 6 - [[1,2-diphenyl 5 [[[(4-trifluoromethyl) phenyl] sulf] isopropyl ester onyl] amino] 1H-benzimidazol-6-yl] oxyN] -hexanoic acid isopropyl ester nab - [[5 - [[[4- (acetylamino) phenyl] sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6- 6 - [[5 - [[bis (3-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6-yl] oxy] hexanoic acid - [[1,2-diphenyl-5 [(propylsulfonyl) amino] -1H-benzimidazol-6yl] oxy] hexanoic acid 6 - [[5 - [(benzylsulfonyl) amino] -1,2-diphenyl] isopropyl ester -1H-benzimidazol-6-yl] oxy] hexanoic acid 2- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy methyl ester ] ethoxy] acetic acid 3- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] propanoic acid 6 - [[1- (3-nitrophenyl) -2-phenyl- 6 - [[4-acetyl-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6- (1-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[2-Phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazole- [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid 5-yl] 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 methyl ester 6 - [[2-phenyl-1- (3-thienyl) - 1H-Benzimidazol-6-yl] oxy] hexanoic acid 4 - [(1,2-defenyl-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

H1-dimethyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

N-isopropyl-6 - [(1,2-diphenyl-1 H-benzyl)

65858 B1 midazole-6-oxy] hexanamide

6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-pyrrolidin-1-ylhexan-1-one methyl ester of 5 - [[5 - [[(4-chlorophenyl) 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- 6 - [[4- (acetyloxy) -1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester of benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[4-hydroxy-1- (4methylphenyl) ) -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- (4methylphenyl) -2 6- [phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6- [[2-phenyl-1- (3-pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester. [2-Phenyl-1- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2-phenyl-1- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] methyl ester] 6 - [[2- (4-Fluoro-phenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[2- (4-methoxyphenyl) 1 -phenyl-1 6 - [[2- (4-bromophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[2- [-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 4- (Trifluoromethyl) phenyl] -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1-phenyl-2- (benzothien-2-yl) -1H-benzimidazole- 6-yl] oxy] hexanoic acid

6 - [[1-Phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[5-hydroxy-1 (4-methylphenyl) -2- phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid

6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5-methoxy-1- (4methylphenyl) - 6 - [[5-hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid 2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester 6 - [[5-methoxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1 methyl ester - (3,4-Dimiphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -2- (4 -fluorfenes l) -1- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino-1- (4-methoxyphenyl) - 2 (methoxyphenyl) -1H-bimidazol-6-yl] oxy] hexanoic acid 4 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl] H methyl ester -Benzimidazol-6-yl] oxy] butanoic acid methyl ester of 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl] H-benzimidazol-6-yl] 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester of Nab - [[oxy] pentanoic acid methyl ester 5 - [[(4- (trifluoromethyl) phenyl) sulfonyl] amino] -1- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid 6 - [[5 - [[(4 -chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (indan-5-yl) -2-phenyl] methyl ester - 1H-benzimidazol-6-yl] oxy] hexanoic acid

6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[1- (3-fluorophenyl)

65858 Bl

6 - [[2- (4-Nitrophenyl) -1 phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1-Phenyl-2- (3-pyridinyl) 1 H -benzimidazol-6-yl] oxy] hexanoic acid

T4- (cyclopropylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

L1-isobutoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

T4- (cyclopropylmethoxy) -6- [2-phenyl-1 (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6yl] oxy hexanamide

N-Isobutyl-6- [2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy hexanamide

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

14- (3-methoxypropyl) -6 - [(1,2-diphenyl1H-benzimidazol-6-yl) oxy] hexanamide,

N-H306ynin-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] 1-morpholin-1-ylhexan-1-one

N ((2-methoxyethyl) -6 - [(1,2-diphenyl) N-benzimidazol-6-yl) oxy] hexanamide

B1-isopentyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

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

N- (pyridin-3-yl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

N-isopropyl-6-C 1- (3,4-dimethylphenyl) -2-phenyl-1H-idazol-6-yl] oxy] hexanamide

N, N-dimethyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

B1, b [-diethyl-6 - [[1- (3,4-dimethylphenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

N-isobutyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

L1-cyclopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

B1-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-benzimidazol-6-yl] oxy] -1- (2-methoxymethyl) -pyrrolidin-1-ylhexan-1-one

14- (3-imidazol-1-yl-propyl) -6 - [[1- (3,4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide

N- (2-pyridin-2-ylethyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanamide

N- (3-methoxypropyl) -6 - [[1- (indan-5-yl) 2-phenyl-1H-benzimiazol-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- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

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 methyl ester

6 - [[2- (3-Indolyl) -1- (4methylphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

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 methyl ester

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

The benzimidazole derivatives of the invention impede the activation of microglia and can therefore be used to produce drugs intended to treat or prevent diseases associated with microbes. Microglia should be understood here as macrophages of the brain.

This action is surprising since so far only benzimidazole derivatives used for the treatment of thrombosis and arteriosclerosis have been described (EP 0531883, WO 1998/007263, EP

65858 Bl

0104727, WO 1997/012613), cysts (WO 1997/033873), and diseases associated with beta-amyloidpeptide (US 5,552,426) and one potent activation of Ca-channels (EP 520200), however, no known effect on microglia.

The invention also relates to the use of a benzimidazole of formula II

wherein

R ¹ means a mono- or bicyclic group of 6-12 carbon atoms or a mono- or bicyclic 5-1 membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, such as aryl or heteroaryl groups may be independently substituted with the following substituents:

F, Cl, Br, I, 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, XCONR ⁴ R ⁴ ', XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , SO2NR ⁴ R ⁴ ', no2, xnh ₂ , xnhr ⁴ , xnr ⁴ r ⁴ , xnhso ₂ r ⁴ , XN (SO2R ⁴ ) (SO2R ⁴ '), XNR ⁴ SO ₂ R ⁴ ', xnhcor ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxypyrrole-1 - yl, 2,5-dihydro-2,5-dioxypyrrol-1 yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, R ⁴ as two substituents on R ¹ when positioned relative to each other in ortho position, may be so interconnected that together they may form metaandiylbisoxy, ethane-1,2diylbisoxy, propane-1,3-diyl, butane-1,4-diyl,

R ² means one mono- or bicyclic aryl group having 6-10 carbon atoms or one mono- or bicyclic 5-10 membered heteroaryl group with 1-4 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, as indicated aryl or heteroaryl groups may be independently substituted with the following substituents:

F, Cl, Br, I, 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, XCONR ⁴ R ⁴ ', XCONHR ⁴ , XCONHOH, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , XSOR ⁴ , XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , are ₂ nr ⁴ r ⁴ ', no2, xnh2. xnhr ^4, xNR ⁴ R ^4, XNHS02R ^4, XN (S02R ⁴⁾ (S02R ⁴ '), xnr ⁴ so ₂ r ^4', XNHCOR ^4, XNHCOOR ^4, XNHCONHR ^4, tetrahydro-2,5-dioxopyrrole-1-yl , 2,5-dihydro-2,5-dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, R ⁴ as two substituents on R ² when positioned relative to each other in ortho position , can be bonded together to form together methandiylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane 1,4-diyl,

R ³ means one or two substituents which independently represent hydrogen,

F, Cl, Br, I, 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 ', no ₂ , xnh ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', xnhso2r ⁴ , XNR ⁴ SO2R 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, R ⁴ as two of the substituents on R ³ , when positioned relative to each other in the ortho position, may be bonded together to form methandiylbisoxy, ethane-1,2diylbisoxy, propane-1,3-diyl, butane-1,4-diyl ,

R ⁴ and R ⁴ 'independently of one another denote perfluoroalkyl of 1-4 carbon atoms, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-7 carbon atoms , (C, ₃ alkyl-C _3-7 cycloalkyl), C ₁₃ alkyl-C ₆₁₀ aryl, C ₁₃ alkyl 5-10 membered heteroaryl having 1 to 4 nitrogen, sulfur or oxygen atoms, aryl having 6 10 carbon atoms or 5- 10-membered heteroaryl having 1-4 nitrogen, sulfur or oxygen atoms, the aryl groups having 6 to 10 carbon atoms and heteroaryl groups may be substituted by one or two substituents from the group having

65858 Bl is fluorine, chlorine, bromine, methyl, ethyl, NO ₂ , methoxy, ethoxy, CF ₃ , C ₂ F _5, or may also contain an annealed methandylbisoxy-, ethane-1,2-diylbisoxyrup, such as in a 5 membered cycloalkyl ring one member of the ring may be one nitrogen or one oxygen and in a 6- or 7 membered cycloalkyl ring one or two of the ring members may be nitrogen and / or oxygen, the ring nitrogen being optionally may be substituted with alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms,

R ⁵ and R ⁵ 'independently of one another denote hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, one carbon atom being replaced by oxygen, sulfur, SO, SO ₂ , NH, NI ₃ alkyl or NC _w alkanoyl,

C _3-7 cycloalkyl-C _0-3 alkyl, wherein in one 5-membered cycloalkyl ring one member of the ring may be one nitrogen or one oxygen and in one 6- or 7-membered cycloalkyl ring one or two of the members of the ring may be nitrogen and / or oxygen, the ring nitrogen may optionally be substituted with alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms, aryl of 6 to 10 carbon atoms or 510 membered heteroaryl of 1 to 4 nitrogen, sulfur and oxygen heteroatoms, said alkyd, alkenyl and alkynyl chains being said to be m substituted already mentioned cycloalkyls, aryls or heteroaryls, each of the foregoing alkyl and cycloalkyl radicals can be substituted with up to two substituents from CF _3, CjFj, OH, _C13 alkyl, NH _2, NH C ₁₃ alkyl, NH C _b3 alkanoyl, N (C ₁₃ alkyl) ₂ , N (C ₁₃ alkyl) (C ₁₃ alkanoyl), COOH, CONH ₂ , COO C _{] 3} alkyl and all the above aryl and heteroaryl groups may be substituted with one or two substituents from the group consisting of F, Cl, Br, CH ₃ , CD, NO ₂ , OCH ₃ , OSD, CF ₃ , C ₂ F _5, or may contain one annealed methacdylbisoxy, ethane-1,2-diylbisoxy group, or R ⁵ and R ⁵ ' stituted together with the nitrogen atom a 5-7-membered heterocycle which can contain another oxygen, nitrogen or sulfur atom and can be substituted by alkyl having 1 to 4 carbon atoms, C _m C _{0 alkoxy-2-alkyl, 143} alkoxycarbonyl, aminocarbonyl or phenyl.

A represents alkandiyl of 1 to 10 carbon atoms, alkenediyl of 2 to 10 carbon atoms, alkindiyl of 2 to 10 carbon atoms, (C 1-6 alkanediyl-C _{3 7} cycloalkanediyl-C _{0 5} alkanediyl), (C ₀₅ alkanediylaryl-C ₀₅ alkanediyl) ) (C _{0. 5} alkanediyl-heteroaryl-C ₀₅ alkanediyl), the groups aryl and heteroaryl can be substituted with one or two substituents selected from fluorine, chlorine, bromine, methyl, ethyl, nitro, methoxy, ethoxy, CF _3, C ₂ F _5, in a 6- or 7-membered cycloalkyl ring one or two of the ring members may be nitrogen and / or oxygen, nitrogens of the ring in an case can be substituted by alkyl having 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms, as in the above aliphatic chains one or two carbon atoms may be replaced with 0, NH, NR ^4, NCOR ^4, NSO ₂ R ⁴ , wherein the alkyl or cycloalkyl groups may be substituted by one or two substituents of F, OH, OR ⁴ , OCOR ⁴ , = O, NH ₂ , NR ⁴ R ⁴ ', NHCOR ⁴ , NHCOOR ⁴ , NHCONHR ⁴ , NHSO 4 SH, SR ⁴ ,

B means 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 , SO3H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO2NR ⁵ R ⁵ ', PO3H, PO (OH) (OR ⁵ ), PO ( OR ⁵ ) (OR ⁵ '), PO (OH) (NHR ⁵ ), PO (NHR ⁵ ) (NHR ⁵ ), tetrazolyl usually bonded to one carbon atom of group A, or represents the general group YAB N (SO ₂ R ⁴ ) (SO2R ⁴ ') mhNHSO2R ⁴

X stands for one bond, CH ₂ , (CH ₂ ) ₂ , CH (CH ₃ ), (CH ₂ ) ₃ , CH (CH ₂ CH ₃ ), CH (CH ₃ ) CH ₂ , with dimethyl

Y means a bond, O, S, SO, SO ₂ , NH, NR ⁴ , NCOR ⁴ , NSO ₂ R ⁴ , for the preparation of medicaments for the treatment or prevention of diseases associated with the activation of microglia.

General formula II includes, in addition to the new compounds of general formula I, known compounds (EP 0 531 883, DE 4330959). The compounds of general formula II inhibit microglia activation.

This action is also new to known compounds.

65858 Bl

It is preferred to use compounds of general formula II in which

R ¹ denotes one mono- or bicyclic aryl group, or one mono- or bicyclic 510-membered heteroaryl group having 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, said aryl or heteroaryl groups being independently substituted by up to three of the following substituents:

F, C1, Br,

HON, 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 , NO2, XNHR ⁴ , XNR ⁴ R ⁴ ', R ⁴ , being two of the substituents to R ¹ , when positioned in the ortho position with respect to each other, can thus be interconnected to form together methandylbisoxy, ethane 1,2-diylbisoxy, propane-1,3-diyl, butane-1,4diyl.

It is also preferred to use compounds of general formula II when

R ² denotes one mono- or bicyclic aryl group or one mono- or bicyclic 510-membered heteroaryl group of 1 -2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, said aryl or heteroaryl groups independently of one another may be replaced by up to three of the following substituents:

F, C1, Br, HON, 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, xso2r ^4, so2nh _2, so ₂ nhr ^4, so ₂ nr ⁴ r ⁴ ·, no2, XNH2, XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XN (SO2R ⁴ ) (SO2R ⁴ '), XNR ⁴ SO ₂ R ⁴ ', xnhcor ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , R ⁴ . wherein two of the substituents on R ² , when positioned relative to each other in the ortho position, can thus be coupled to each other to form together methanediylbisoxy, ethane 1,2,2-diylbisoxy, propane-1,3-diyl, ethane- 1,4diil.

It is also preferred to use compounds of general formula II in which

R ³ represents hydrogen,

F, C1, Br, HON, 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 , XSO2R ⁴ , SO ^, so2nhr ⁴ , SO2NR ⁴ R ⁴ ', NO2, XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XNR ⁴ SO2R ⁴ ', XN (SO2R ⁴ ) (SO2R ⁴ '), XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ or R ⁴ , where the two substituents R ³ , when positioned in ortho position with respect to each other, can be so linked together that they form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl,

Also preferred are compounds of general formula II when

R ⁴ and R ⁴ 'independently of one another denote CF ₃ , C ₂ F ₅ , alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, alkynyl of 2 to 4 carbon atoms, cycloalkyl of 3 to 6 carbon atoms , (C] ₃ alkyl-C _3-6 cycloalkyl), alkylaryl of 1 to 3 carbon atoms, alkylheteroaryl of 1 to 3 carbon atoms, monocyclic aryl or 5-6 membered heteroaryl of 1-2 nitrogen, sulfur or oxygen atoms, such as the aryl and heteroaryl group may be substituted by one or two substituents of the group F, Cl, Br, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ , or may to contain annulled and the methanediylbisoxy or ethane-1,2-diylbisoxy group, furthermore in one 5-membered cycloalkyl ring one member may be one nitrogen or one oxygen, and in one 6-membered cycloalkyl ring one or two of the ring members may are nitrogen and / or oxygen, the ring nitrogen may optionally be substituted by alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms.

Also preferred are compounds of general formula II when

R ⁵ and R ⁵ 'independently of one another denote alkyl of 1 to 6 carbon atoms, one carbon atom being substituted by Ο, NH, N C _1-3 alkanoyl

C _3-7 cycloalkyl-C _0-3 alkyl, wherein in one 5-membered cycloalkyl ring one member of the ring may be one nitrogen or one oxygen, and in one 6- or 7-membered cycloalkyl ring one or two of the ring members may be may be one or two nitrogen and / or oxygen, the ring nitrogen may optionally be substituted by

65858 B1 alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms, said alkyl moiety having 1 to 6 carbon atoms may be replaced by one of the above cycloalkanes or by one to 5-6 membered heteroatoms, selected from the group consisting of nitrogen, sulfur or oxygen, all of the already mentioned alkyl and cycloalkyl moieties being substituted by up to two substituents of CF ₃ , OH, C 1 -C ₁₃ alkyl, and the above heteroaryl groups may be substituted with one or two substituents from F, Cl, CF _3, CH _3, C ₂ H _5, OCH _3, OC ₂ H _5, or R ⁵ u R ⁵ 'ZAED o with the nitrogen form a 5-7-membered heterocycle which can contain another oxygen, nitrogen or sulfur atom and can be substituted by alkyl having 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms, C _1-4 alkoxy -C ₀₂ alkyl, C ₁₄ alkoxycarbonyl, aminocarbonyl or phenyl.

It is also preferred to use compounds of general formula II when

A represents alkanediyl having 1 to 10 carbon atoms, alkenediyl having 2 to 10 carbon atoms, alkindiil having 2 to 10 carbon atoms, (C _{0 5} alkanediyl-C _{3 7} cycloalkanediyl-C _{0. 5} alkanediyl), or _{(o 5} alkandiil- C _{3 7} cycloalkanediyl-C ₀ _ ₅ alkanediyl), or (C ₀₅ alkanediyl-heteroaryl-C ₀₅ alkanediyl), and optionally one available heteroaryl group may be substituted with one or two substituents from F, C1, Br, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ^ CF ₃ , C ₂ F ₅ , and in addition in one 5-membered cycloalkyl ring one member of the ring may be one nitrogen or one oxygen, and in one 6- or 7- membership cycle an alkyl ring one or two of the ring members may be nitrogen and / or oxygen, the ring nitrogen may optionally be substituted with alkyl of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms, such as in an aliphatic chain one or two of the carbon atoms thereon can be replaced by O, NH, N _C1-3 alkyl, N C ₁₃ alkyl, N C _yz alkanoyl, NSO ₂ C ₁₃ alkyl, and in this the alkyl or cycloalkyl moiety may for be substituted by up to two fluorine atoms or with one of the substituents OH, O C ₁₃ alkyl, O C ₁₃ alkanoyl, = O, NH ₂ , NHC ₁₃ alkyl, N (C _{) 3} alkyl) ₂ , NH C _3-3 alkanoyl, N (C ₁₃ alkyl), (C ₁₃ alkanoyl), NHCOO C ₁₃ alkyl, NHCONH C ₁₃ alkyl, NHSO ₂ C ₃ alkyl, SH, C ₁₃ alkyl.

It is also preferred to use compounds of general formula II when

B represents hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COOH, COOR ⁵ , CONH ₂ , CONHR ⁵ , CONR ⁵ R ⁵ ', CONHOH, CONHOR ⁵ or tetrazolyl, usually bonded to a carbon atom of city A.

It is also preferred to use compounds of general formula II when

X stands for single bond or CH ₂ .

It is also preferred to use compounds of general formula II when

Y represents a bond, O, S, NH, NR ^4, NCOR ⁴ mniNSO ₂ R ^4.

Example 307 describes how to measure the inhibition of microglia activation. Activation of microglia can be stimulated by various stimuli, such as Abeta-peptide (beta-Amyloid, Araujo, D. M. and Cotman, S. M. Brain Res. 569, 141-145 (1992)), prion protein , cytokines, or through parts of cells (Combs, K. K. et al. (1999) J. Neurosci., 19, 928-939; Wood, PL (1998) Neuroinflammation: Mechanismus and Management, Humana Press). For example, the compound of Example 49 is 6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester shows a retention of IC ₅₀ = 0.75 µM.

Abeta-peptide stimulation responds to the pharmacological status of Alzheimer's disease. In this test, the substances of the invention show, upon stimulation with Abetapeptide, a delay in the activation of microglia. Delayed activation of microglia by the substances of the invention results in a strong reduction in cytokine production and cytokine secretion, eg from II1 beta and 10alpha (measured by ELISA and mRNA extended analysis), and impeded reactive oxygen / nitrogen secretion . Therefore, multiple inflammatory factors are retained at the same time.

The in vivo action of the substances of the invention is shown in an ICAO model in rats. This model simulates the state of an impact case. The substances according to the invention reduce the activation of

65858 Bl microglia, which in acute form occurs in animals.

The invention also relates to the use of compounds of general formula I and general formula II according to the invention for the preparation of medicaments for the treatment and prophylaxis of diseases associated with the activation of microglia. Examples of such diseases are AIDS - dementia, amyotropic lateral sclerosis, Creutz-Jacob disease, Dowens syndrome, diffuse Lewy Body disease, Huntington's disease, leukoseptalopathy, multiple sclerosis, Parkinson's disease, Pickser's disease, stroke , temporal lobe epilepsy and tumors.

The invention also relates to pharmaceutical agents containing one or more compounds of formula I of the invention and one or more carriers. The pharmaceutical agents, for example the compositions according to the invention are prepared in a known manner with the usual solid or liquid carriers or diluents and the usual pharmaceutical and technical auxiliaries corresponding to the desired dosage form. Preferred dosage forms consist of a single dosage form suitable for oral, enteral or parenteral administration. Such dosage forms are, for example, tablets, film coated tablets, dragees, pills, capsules, powders or depot forms as well as suppositories. Appropriate tablets can be prepared by mixing the active substance with known adjuvants, such as inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinylpyrrolidone, explosives such as corn starch or alginic acid, binders such as starch or gelatin, carboxylic acid-facilitating agents , carboxymethylcellulose, cellulose acetate phthalate or polyvinyl acetate. Tablets may also consist of multiple layers.

Accordingly, dragees can be obtained by coating the obtained cores, similar to tablets, with conventional dragee coatings used, for example, polyvinylpyrrolidone or shellac, arabic gum, talc, titanium oxide or sugar. In this case, the coating of the dragees may consist of several layers, and the excipients mentioned above for the tablets may be used here.

Capsules containing the active substance may be prepared, for example, by mixing the active substance with an inert carrier such as milk sugar or sorbitol and then filling the gelatin capsules.

Substances of the invention, placed in suitable solutions, such as sodium chloride saline, can be used as infusion or injection solutions.

In particular, oily solutions such as sesame oil, castor oil and cottonseed oil are used for parenteral administration. Solubility agents such as benzylbenzoate or benzyl alcohol may be used to increase solubility.

It is also possible that the substances according to the invention can be processed into a transdermal system and thus used.

The dosage of the substances of general formula I according to the invention and of general formula II is determined by the treating physician and depends, inter alia, on the substance taken, the route of administration required for the disease being treated and the severity of the disease. The daily dose does not exceed 1000 mg, preferably not more than 100 mg, the dose may be taken as a single dose or divided into two or more daily doses.

The compounds of the invention of general formula I may be as tautomers, stereoisomers or geometric isomers. The invention includes all possible isomers such as E- and Z-isomers, S- and R-enantiomers, diastereomers, racemates and mixtures thereof including those of tautomeric compounds.

The isomeric mixtures may be separated into enantiomers or E / Z-isomers in the usual manner, such as crystallization, chromatography or salt formation.

The preparation of the compounds according to the invention proceeds analogously to known methods, which are described, for example, in EP 531 883. Insofar as the preparation of the starting compounds is not described, these starting compounds are known or may be purchased or prepared.

65858 The preparation blend is analogous to the methods described herein. The example preparation in some preliminary steps, the preparation of intermediates and products, will be described below.

For example, the following methods are used to prepare the substances according to the invention.

General Job Prescription 1:

Nitro group reduction, double bond hydrogenation and hydrogenolytic cleavage of benzyl ethers

The reducing compound was dissolved in ethyl acetate; tetrahydrofuran, methanol or ethanol or solvent mixtures and palladium-on-charcoal (10%) was hydrogenated at normal pressure on 2.5% (nitro compound). After the end of hydrogenation was sucked off, the residue was washed with ethyl acetate or methanol or ethanol and the filtrate was concentrated in vacuo. As a rule, the product is further converted without further purification.

General Prescription for Job 2:

Reduction of nitro groups

9.2 g of ferric (II) sulfate were placed in 30 ml of water and 9 ml of ammonia solution. A solution of 3.6 mmol nitro compound in 100 ml ethanol was added dropwise and the suspension was stirred vigorously for 1 hour at 70 ° C. Finally, it was allowed to precipitate, filtered off the solid, the filtrate was concentrated, mixed with water and extracted three times with ethyl acetate. The combined extracts were dried over sodium sulfate and concentrated in vacuo. The amino compound is further processed as a crude product.

General Prescription for Job 3:

Cyclization to benzimidazoles with mmol orthoesters of 1,2-diaminobenzene derivatives was dissolved in 25 ml of ethanol. 47 ml of a 0.8 M ether solution of HCl were added dropwise, stirred for 30 min and concentrated in vacuo to dryness. The residue was absorbed in 230 ml of methanol and mixed with 6 ml of trimethylorthobenzoate or the corresponding amounts of another orthoester. It is heated for 2-8 h as counter-current, after cooling it is poured onto a solution of sodium bicarbonate, extracted three times with ethyl acetate, the combined extracts dried over sodium sulfate and concentrated in vacuo. The residue was purified by crystallization or column chromatography on silica gel.

General Job Prescription 4:

Cyclization to benzimidazoles with iminoester hydrochlorides

1.2 mmol of a 1,2-diaminobenzene derivative was dissolved in 5 ml of tetrahydrofuran, mixed with 1.5 mmol of benzimidahydrochloride, and the mixture was stirred for 15 min. The starting mixture was mixed with saturated sodium bicarbonate solution, diluted with water and extracted three times with ethyl acetate. The combined organic phases were washed three times with 1 N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulfate, filtered through a silica gel frit, and the solution concentrated to dryness. The product crystallizes from diisopropyl ether.

General Prescription for Job 5:

Cyclization to benzimidazoles via carboxylic acid anilides

4.7 mmol of 1,2-diaminobenzene derivatives were dissolved in 20 ml of dichloromethane, mixed with 14 mmol of triethylamine and slowly mixed with 6 mmol of carboxylic acid chloride and the resulting mixture stirred for 15 h. The mixture was mixed with saturated sodium bicarbonate solution, diluted with water and extracted twice with dichloromethane. The combined organic phases were washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The remaining crude carboxylic acid anilide was adsorbed in a 9: 1 mixture of methanol and conc. hydrochloric acid and stirred for 1 h countercurrent. After cooling, the reaction mixture was slowly added to saturated sodium bicarbonate solution, diluted with water and extracted three times with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. If necessary, the residue is purified by crystallization or column chromatography on silica gel.

General Prescription for Work 6:

65858 Bl

The ether cleavage with hydrobromic acid g arylmethyl ether is mixed with 160 ml of 48% aqueous hydrobromic and heated for 1 to 5 hours. After cooling, it is filtered. The residue was taken up in ethyl acetate and extracted three times with saturated sodium bicarbonate solution. After drying over sodium sulfate, it was concentrated in vacuo. If necessary, the residue is purified by crystallization or column chromatography.

General Job Prescription 7:

Ether cleavage with boron tribromide

1.86 mmol of arylmethyl ether was dissolved in 18 ml of dichloromethane and slowly mixed with 7.4 ml of a 1M solution of boron tribromide in dichloromethane at -35 ° C. It is left to stand for 12-15 h at 30 ° C, then mixed with saturated sodium bicarbonate solution, extracted three times with dichloromethane, the combined extracts dried over sodium sulfate and concentrated in vacuo. If necessary, the residue was purified by silica gel column chromatography.

General Job Prescription 8:

Alkylation of hydroxybenzimidazole derivatives and phenolic derivatives with alkyl halides

A solution of 1.85 mmol of hydroxybenzimidazole derivatives in 12 ml of N, N-dimethylformamide is mixed with 1.85 mmol of cesium carbonate and 2.24 mmol of alkyl bromide or alkyl iodide. A maximum of 1.85 mmol of sodium iodide is mixed using alkyl bromides. It was stirred for 12-96 h, poured into water, absorbed into ethyl acetate, the organic phase was washed four times with water, dried over sodium sulfate and concentrated in vacuo.

Alternatively to this aqueous treatment, the reaction mixture can be mixed with dichloromethane, separated from the precipitated salts by filtration and the filtrate concentrated in vacuo.

Regardless of the treatment method, the residue is purified by crystallization or column chromatography.

General Prescription for Work 9:

Saponification of carboxylic acid alkyl esters

Carboxylic acid alkyl ester of 0.77 mmol was dissolved in 5 ml of methanol and 5 ml of tetra hydrofuran was mixed with 5 ml of 0.5 N aqueous sodium hydroxide solution. After stirring for 2-12 h, it was concentrated in vacuo, neutralized by the addition of aqueous hydrochloric acid and extracted with ethyl acetate. It was dried over sodium sulfate and concentrated in vacuo. If necessary, the residue was purified by silica gel column chromatography.

General Requirement for Work 10: Carboxylic acid saponification 0.2 mmol of carboxylic acid are dissolved in 1 ml of primary or secondary alcohol, mixed with two drops of conc. sulfuric acid and stirred for 12 hours at 60 ° C. The mixture was then mixed with saturated potassium bicarbonate solution, diluted with water and extracted three times with ethyl acetate. After washing, the combined extracts with saturated sodium chloride solution and drying over sodium sulfate were concentrated in vacuo and the residue was crystallized from diisopropyl ether.

General Prescription for Work 11:

Reduction of alkyl esters of carboxylic acids with lithium aluminum hydride

Carboxylic acid ester of 0.15 mmol was dissolved in tetrahydrofuran and mixed with 0.09 mmol of lithium aluminum hydride. It was stirred for 1-48 hours, mixed with water and extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. If necessary, the residue is purified by crystallization or by column chromatography on silica gel.

General prescription for work 12:

Wittig reaction for benzimidazolecarbaldehydes with (omega-carboxyalkyl) triphenylphosphonium bromides and esterification with methanol mmol (omega-carboxyalkyl) triphenylphosphonium bromide were mixed in 2.5 ml dimethylsulfoxide and 2.5 ml temp. stirred for 30 min at> 10 ° C. Finally, a solution of 0.67 mmol aldehyde in 2 ml of tetrahydrofuran was added and stirred for 3 h at 20 ° C. The solution was then mixed with saturated ammonium chloride solution, diluted with water and extracted three times with ethyl acetate. After drying the combined organs

65858 B1 phases over sodium sulfate were concentrated in vacuo. The residue was dissolved in 15 ml of methanol, mixed with two drops of conc. sulfuric acid and allowed to stand for 48-72 h. After concentration in vacuo, the residue was purified by silica gel column chromatography.

General prescription for work 13:

Conversion of aminobenzimidazoles with alkyl halides and arylsulfonic acids The micromol aminobenzimidazole derivative is dissolved in 0.5 ml of dichloromethane, mixed with 51 micromol triethylamine and 51 micromol halide of the alkyl or arylsulfonic acid 2-hydroylsulfonic acid-15 sulfuric acid mixture. For the treatment, saturated sodium bicarbonate solution was added, extracted three times with dichloromethane, the combined organic phases were washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was purified by crystallization or column chromatography on silica gel.

General Prescription for Work 14:

The 0- or N-arylation of benzimidazoles with the aid of copper mmol The N-unsubstituted benzimidazole derivative or one N-substituted hydroxybenzimidazole derivative was dissolved in 20 ml of dichloromethane. Add 10 mmol of arylboronic acid, 5 mmol of anhydrous copper (II) acetate, 10 mmol of pyridine or triethylamine and about 2.5 g of molecular sieve (4), stir for 48-72 h with moisture off, add silica gel, concentrate is vacuum-dried and the remaining powder is purified by chromatography on silica gel. The regioisomeric N-aryl products are separated, if necessary, by HPLC.

General Prescription for Work 15:

N-Substituted Benzimidazoles Catalyzed With Base mmol The N-unsubstituted benzimidazole derivative was dissolved in 20 ml of dimethylacetamide. 25 mmol of an electron-poor aryl- or heteroaryl-halide was added and heated for 48-72 h while removing the counter-current moisture, then silica gel was added, concentrated in vacuo to dryness and the remaining powder was purified by chromatography on silica gel. The regioisomers and aryl products are separated if necessary by HPLC.

General Prescription for Work 16:

Cyclization to benzimidazoles with aldehydes mmol 1,2-diaminobenzimidazole derivatives dissolve 3 ml of nitrobenzene. 1 mmol of aryl, respectively, heteroaryl aldehyde, was added. Heat for 2 to 6 hours at 150 ° C and allow to cool. The residue was subjected, without further treatment, to direct purification by silica gel column chromatography.

General Prescription for Work 17:

Conversion of carboxylic acids to carboxylic acid amides

0.25 mmol of carboxylic acid was dissolved in 3 ml of N, N-dimethylformamide, mixed with 0.38 mmol of primary or secondary amine, 0.5 mmol of triethylamine and 0.25 mmol of diphenylphosphorylase, and the mixture was stirred for 2 h. For the treatment, water was added, extracted three times with ethyl acetate, the combined organic phases were washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography.

General Job Prescription 18:

Conversion of carboxylic acid esters to carboxylic acid amides

0.36 mmol amine was dissolved in 3 ml of toluene and, while cooling in an ice bath, was mixed dropwise with 0.18 ml of a 2M solution of trimethylaluminum in toluene. It was mixed with a solution of 0.33 mmol of carboxylic acid methyl ester in 3 ml of toluene and stirred for 2 - 8 hours at 95 ° C. For the post-cooling treatment, water was added, extracted three times with ethyl acetate, the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography.

Examples of carrying out the invention

Example 1

[(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] acetic acid isopropyl ester is obtained by conversion of 1,2-di

65858 B1 phenyl-6-hydroxy-1H-benzimidazole (Benincori, T .; Sannicolo, F .; J. Heterocycl. Chem; 25; 1988; 1029-1033) with isopropyl ester of bromoacetic acid according to general prescription 8 .

Flash point (bp) 137-138 ° C

Example 2 [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethan-1-ol was prepared by converting the methyl ester of [(1,2-diphenyl-1H-benzimidazol-6-yl) hydroxyacetic acid (DE 4330959) according to general prescription 11.

Ή-NMR (D ₆ -DMSO); delta = 3.72 ppm t (J = 7.5 Hz, 2H); 4.021 (J = 7.5 Hz, 2H); 6.72 d (J = 2 Hz, 1H); 7.10 dd (J = 8.2 Hz, 1H); 7.38-7.68 m (10H); 7.76 d (J = 8 Hz, 1H).

Example 3

3- [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] propan-1-ol

0.5 g of 1,2-diphenyl-6-hydroxy-1H-benzimidazole are mixed as prescribed for operation 8 with 3- (bromopropoxy) -t-butyldimethylsilane. After chromatography on silica gel, it was absorbed in 2.5 ml of methanol, 0.4 ml of conc. hydrochloric acid and stirred for 2 h at 20 ° C. It is poured into saturated sodium bicarbonate solution, extracted three times with ethyl acetate, the combined extracts washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo.

D.C. 191-193 ° C

Example 4

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

100 mg of 3 - [(1,2-diphenyl-1H-benzimidazol6-yl) oxy] propan-1-ol were placed in 2.5 ml of acetone and mixed at a temperature of -15 ° C with a solution of Jones reagents (obtained from 0.27 g of Scheme (Y1) oxide, 1 ml of water and 0.23 ml of concentrated sulfuric acid). After stirring for 3.5 h, it was saturated by the addition of isopropanol. It was diluted with water, extracted three times with dichloromethane, the combined organic phases were dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography.

1 H-NMR (D ₆ -DMSO): delta = 2.60 ppm t (J = 7.5 Hz, 2H); 4.151 (J = 7.5 Hz, 2H); 6.64 d (J =

Hz, 1H); 6.95 dd (J = 8.2 Hz, 1H); 7.30-7.61 m (10H); 7.69 d (J = 8 Hz, 1H).

Example 5

3 - [(1,2-Diphenyl-1H-benzimidazole-) oxy] propanoic acid methyl ester mg 3 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid was dissolved in 0.5 ml of Ν, Ν- dimethylformamide and mixed with 41 mg of cesium carbonate and 10 microl of methyl iodide. It was stirred for 2 h, diluted with dichloromethane, filtered, the filtrate was concentrated in vacuo and the residue was chromatographed on silica gel.

D.C. 120-121 ° C

Example 6

2 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid methyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 2-bromopropanoic acid methyl ester according to the general prescription 8.

D.C. 132-135 ° C

Example 7

4 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] butanoic acid isopropyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 4-bromobutanoic acid isopropyl ester according to general prescription 8.

D.C. 89-91 ° C

Example 8

4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butan-1-ol is obtained by the conversion of 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy methyl ester ] butanoic acid according to general prescription 11.

D.C. Mp 159-160 ° C

Example 9

Acetic acid [4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] but-1-yl] ester mg 4 - [(1,2-diphenyl-1H-benzimidazol-benzimidazol-6-yl) oxy] butane The 1-ol was dissolved in 1 ml of dichloromethane, mixed with 0.34 ml and 20 µl of acetyl chloride and stirred for 15 h. It is mixed with saturated sodium bicarbonate solution, diluted with water, extracted twice with dichloromethane, the combined organic phases washed with saturated sodium chloride solution, dried over sodium

65858 B1 chloride and concentrated in vacuo. The residue was purified by flash chromatography.

D.C. 68-69 ° C

Example 10

Pivalinic acid [4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] but-1-yl] -ester is prepared analogously to the procedure described in Example 9 of 50 mg 4 - (((1 , 2-diphenyl-1H-benzimidazol-6-yl) oxy] butan-1-ol, 0.34 ml pyridine and 22 microl trimethylacetic acid chloride.

D.C. 104-106 ° C

Example 11

4 - [(1r2-diphenyl-1H-benzimidazol-6-) oxy] butyl-N-methylcarbamate

100 mg of 4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butan-1-ol were dissolved in 4 ml of dichloromethane, mixed with 0.1 ml of triethylamine and 20 mg of methyl isocyanate and stirred for 15 h. New 0.1 ml of triethylamine and 20 mg of methyl isocyanate were added, stirred for 20 h, and concentrated in vacuo. The residue was purified by chromatography on silica gel.

D.C. 124-126 ° C

Example 12

5 - ((1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid 994 isopropyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 5-bromopentanoic acid isopropyl ester. according to general regulations 8.

D.C. 91-92 ° C

Example 13

6 - ((1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexane methyl ester acid according to the general prescription 8.

1 H-NMR (CDCl 3: delta = 1.44-1.56 m (2H); 1.64-1.85 m (4H); 2.331 (J = 7.5 Hz, 2H);

3.66 s (3H); 3.931 (J = 7.5 Hz, 2H); 6.70 d (J = 2 Hz, 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 = 8 Hz, 1H).

Example 14

6 - ((1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanoic acid isopropyl ester according to the general prescription 8.

1 H-NMR (CDCl 3): δ = 1.22 ppm d (J =

7.5 Hz, 6H); 1.43-1.56 m (2H); 1.62-1.87 m (4H); 2.30 t (J = 7.5 Hz, 2H); 3.93 1 (J = 7.5 Hz, 2H); 5.01 sp (J = 7.5 Hz, 1H); 6.69 d (J = 2 Hz, 1H); 6.96 dd (J = 8.2 Hz, 1H); 7.25-7.38 m (5H); 7,437.55 m (5H); 7.75 d (J = 8 Hz, 1H).

Example 15

6 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid is obtained by conversion of 6 - ((1,2-diphenyl-1H-benzimidazol6-yl) oxy] hexanoic acid methyl ester according to the general prescription 9.

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

Example 16

6 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - ((1,2-diphenyl-1H-benzimidazol-6yl) oxy] hexanoic acid according to the general prescription 11.

1 H-NMR (CDCl 3): δ = 1.35-1.85 ppm m (8H); 3.671 (J = 7.5 Hz, 2H); 3,981 (J = 7.5 Hz, 2H); 6.70 d (J = 2 Hz, 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 = 8 Hz, 1H).

Example 17

6 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide

a) 6 - ((1,2-diphenyl-1H-benzimidazol-6yl) oxy] hexanenitrile is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromohexanenitrile according to general prescription 8 .

D.C. 108-112 ° C

6 - ((1,2-diphenyl-1H-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 was added 18 mg of potassium carbonate and 40 µl of a 30% aqueous solution of hydrogen

65858 B1 peroxide and stirred for 24 h. The ice-cold sodium thiosulphate solution was then stirred and extracted three times with ethyl acetate. After drying over sodium sulfate, it was concentrated in vacuo and the residue was chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 1.48-1.60 ppm m (2H); 1.65-1.87 m (4H); 2.251 (J = 7.5 Hz, 2H); 3.941 (J = 7.5 Hz, 2H); 5.30-5.53 Breit (2H); 6.68 d (J = 2 Hz, 1H); 6.95 dd (J = 8.2 Hz, 1H); 7,237.38 m (5H); 7.42-7.58 m (5H); 7.75 d (J = 8 Hz, 1H).

Example 18

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

100 mg of 6 - [(1,2-diphenyl-1H-benzimidazol6-yl) oxy] hexanoic acid was dissolved in 2 ml of tetrahydrofuran, mixed with 39 mg of carbonyl diimidazole, stirred for 30 min at 20 ° C and then this is heated for 30 min. At 20 ° C, 21 mgO-methylhydroxylamine hydrochloride was added and stirred for 18 h. 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, it was concentrated in vacuo and the residue was chromatographed on silica gel.

D.C. 144-145 ° C.

Example 19

N- (phenylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide is obtained by converting 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid with O-benzylhydroxyamine hydrochloride according to the method described in Example 18.

D.C. 144 ° C

Example 20

N-hydroxy-6-K 1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide 3H- (phenylmethoxy) -6 - [(1,2-diphenyl1H-benzimidazol-6-yl) oxy] hexanamide were dissolved in 4 ml of ethanol, mixed with 15 mg of palladium on charcoal (10%) and stirred under hydrogen for 3 h. After separation from the catalyst, it was concentrated in vacuo and the residue was crystallized from diethyl ether.

D.C. 83-85 ° C

Example 21

7 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid methyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with methyl ester of 7- bromoheptanoic acid as described in the general prescription 8.

D.C. 77-80 ° C

Example 22

7 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid is obtained by converting 7 - [(1,2-diphenyl-1H-benzimidazol-6yl) oxy] heptanoic acid methyl ester according to the general prescription 9.

D.C. 142-145 ° C

Example 23

7 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid isopropyl ester is obtained by converting 7 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] heptanoic acid with isopropanol according to the general prescription 10.

D.C. 98-100 ° C

Example 24

6 - [[1- (3-Nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hydroxy-1- (3-nitrophenyl) -2- Phenyl-1H-benzimidazole (DE 4330959) with 6-bromo-hexanoic acid isopropyl ester according to general prescription 8.

Mp 111-113 ° C

Example 25

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

a) (5-methoxy-2-nitrophenyl) [(3-trifluoromethyl) phenyl] amine g 3-fluoro-4-nitroanisole and 16 ml of 3 (trifluoromethyl) aniline were stirred for 72 h at 140 ° C. Finally, the mixture was diluted with ethyl acetate, washed ten times with 4 N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulfate; The mixture was concentrated in vacuo and the residue was chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 3.78 ppm s (3H);

6.42 dd (J = 8.2 Hz, 1H); 6.60 d (J = 2 Hz, 1H); 7.45-7.60 m (4H); 8.22 d (J = 8 Hz, 1H); 9.78 s

65858 B1 (breit) (1H).

b) 6-Methoxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole is obtained by hydrogenation of (5-methoxy-2-nitrophenyl) [(3-trifluoromethyl) phenyl] amine according to the general requirement for work 1 and final cyclization with triethylorthobenzoate according to the general prescription for work 3.

D.C. 135-137 ° C

c) 6-hydroxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole is obtained by converting 6-methoxy-2-phenyl-1 - [(3-trifluoromethyl) phenyl] -1H-benzimidazole according to the general prescription for work 6.

1 H-NMR (D ₆ -DMSO): delta = 6.56 ppm d (J = 2 Hz, 1H); 6.82 dd (J = 8.2 Hz, 1H); 7,327.50 m (5H); 7.60 d (J = 8 Hz, 1H); 7.70-7.95 m (4H); 9.48 s (breit) (1H).

6 - [[2-Phenyl-1- [3- (trifluoromethyl) phenyl] -1H-benzimidazol] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-2-phenyl-1 - [(3-trifluoromethyl) ) phenyl] -1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 106-108 ° C

Example 26

6 - [[2-Phenyl-1- [3 (trifluoromethyl) phenyl] -1H-benzimidazol-6yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hydroxy-2-phenyl-1 - [(3 -trifluoromethyl) phenyl] -1H-benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 113-115 ° C

Example 27

6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] 1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2-phenyl-1- [methyl] 3- (Trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. Mp 156-158 ° C

Example 28

6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] 1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[2-phenyl-1 - [3- (Trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

D.C. 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 g 3-fluoro-4-nitroanisole and 15 ml of 3-aminobenzinitrile were stirred for 65 hours at 140 ° C. Finally, the mixture was diluted with ethyl acetate, washed three times with water and once with saturated sodium chloride solution, dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel, m.p. Mp 157-158 ° C

b) 6-methoxy- (3-cyanophenyl) -2-phenyl-1H-benzimidazole is obtained by hydrogenation of 3- (5-methoxy-2-nitrophenyl) aminobenzonitrile according to the general prescriptions for job 1 and final cyclization with triethylorthobenzoate according to the general prescription 3. For cyclization in deviation with the general prescription, tetrahydrofuran is used as the solvent.

D.C. 185-191 ° C (decomposition)

c) 6-Hydroxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole is prepared by converting 6-methoxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole according to general prescription 7.

D.C. 216-218 ° C

6 - [[1- (3-Cyanophenyl) 2-phenyl-1H-benzimidazol-] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1- (3-cyanophenyl) -2-phenyl-1 H-benzimidazole is 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 115-118 ° C

Example 30

6 - [[1- (3-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hyd

65858Bloxy-1- (3-cyanophenyl) -2-phenyl-1H-benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 101-102 ° C

Example 31

6 - [[1- (3-cyanophenyl) -2-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (3-cyanophenyl) -2-phenyl-1H- methyl ester] benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 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 g 3-fluoro-4-nitroanisole and 15 ml of 4-aminobenzonitrile were stirred for 22 hours at 140 ° C. Finally, the 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, dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

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

b) 6-methoxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole is obtained by hydrogenation of 4- (5-methoxy-2-nitrophenyl) aminobenzonitrile according to general prescription for work 1 and final cyclization with triethylorthobenzoate according to the general prescription for work 3. When cyclising in deviation with the general prescription, tetrahydrofuran is used as the solvent.

1 H-NMR (CDCl 3): δ = 3.82 ppm s (3H);

6.72 d (J = 2 Hz, 1H); 7.00 dd (J = 8.2 Hz, 1H); 7.30-7.49 m (7H); 7.78 d (J = 8 Hz, 1H); 7.81 d (J = 8 Hz, 2H).

c) 6-Hydroxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole is prepared by converting 6-methoxy-1- (4-cyanophenyl) -2-phenyl-1H-benzimidazole according to general prescription 7.

D.C. 266-268 ° C

6 - [[1- (4-Cyanophenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1- (4-cyanophenyl) -2- Phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general working order 8.

D.C. 145-148 ° C

Example 33

6 - [[1- (4-Cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hydroxy-1- (4-cyanophenyl) -2-phenyl- 6-Bromohexanoic acid isopropyl ester 1H-benzimidazole according to general prescription 8.

D.C. 102-103 ° C

Example 34

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

a) 1- (3-Chlorophenyl) -6-methoxy-2-phenyl-1H-benzimidazole is obtained by reduction of (3cyclophenyl) - (5-methoxy-2-nitrophenyl) amine (Belton, Me Inemey; Proc. R. Ir. Acad. Sect. B; 69; 1970; 21,27) according to general prescription for work 2 and final cyclisylation with triethylorthobenzoate according to general prescription for work 3.

D.C. 140-143 ° C

b) 1- (3-Chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole is prepared by converting 6-methoxy-1- (3-chlorophenyl) -2-phenyl-1H-benzimidazole according to general operating instructions 6.

bp 210-214 ° C 6 - [[1- (3-Chlorophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 1- (3cyclophenyl) -6-hydroxy-2 -phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 101-105 ° C

65858 Bl

Example 35

6 - [[1- (3-Cyclophenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by the conversion of 1- (3-chlorophenyl) -6-hydroxy-2-phenyl-1H -benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 107-112 ° C

Example 36

6- [[1- (3-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (3-chlorophenyl) -2- methyl ester] Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.36-1.78 ppm m (6H); 2.241 (I = 7.5 Hz, 2H); 3.96 t (J =

7.5 Hz 2H); 6.68 d (J = 2 Hz, 1H); 6.97 dd (J = 8.2 Hz, 1H); 7.32-7.65 m (9H); 7.69 d (J = 8 Hz, 1H).

Example 37

6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[1- (3-chlorophenyl) ) -2-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

1 H-NMR (CDCl ₃ ): δ = 1.38-1.88 ppm m (8H); 3.671 (J = 7.5 Hz, 2H); 3.961 (J = 7.5 Hz, 2H); 6.70 d (J = 2 Hz, 1H); 6.97 dd (J = 8.2 Hz, 1H); 7.18 ddd (J = 8, 2, 2 Hz, 1H); 7.25-7.55 m (8H); 7.76 d (J = 8 Hz, 1H).

Example 38

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

a) 1- (4-Chlorophenyl) -6-methoxy-2-phenyl-1H-benzimidazole is obtained by reduction of (4-chlorophenyl) - (5-methoxy-2-nitrophenyl) amine (Kottenhahn et al .; J. Org. Chem. ; 28; 1963; 3114, 3118) according to the general prescription for work 2 and the final cyclization with triethylorthobenzoate according to the general prescription for work 3.

1 H-NMR (CDCl ₃ ): δ = 3.82 ppm s (3H);

6.67 d (J = 2 Hz, 1H); 6.97 dd (J = 8.2 Hz, 1H);

7.22-7.40m (5H); 7.46-7.55 m (4H); 7.77 d (J = 8 Hz, 1H).

b) 1- (4-Chlorophenyl) -6-hydroxy-2-phenyl-1H-benzimidazole is prepared by converting 6-methoxy-1- (4-chlorophenyl) -2-phenyl-1H-benzimidazole according to the general prescription of work 6 .

1 H-NMR (D ₆ -DMSO): delta = 6.60 ppm d (J = 2 Hz, 1H); 6.87 dd (J = 8.2 Hz, 1H); 7,407.56 m (7H); 7.64 d (J = 8 Hz, 1H); 7.70 d (J = 8 Hz, 2H); 9.50 s (breit) (1H).

6 - [[1- (4-Chlorophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ether is obtained by converting 1- (4-chlorophenyl) -6-hydroxy-2-phenyl-1H- benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 100-104 ° C

Example 39

6 - [[1- (4-Chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by converting 1- (4-chlorophenyl) -6-hydroxy-2-phenyl-1H -benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 83-88 ° C

Example 40

6 - [[1- (4-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (4-chlorophenyl) -2 methyl ester -phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.35-1.78 ppm m (6H); 2.25 t (J = 7.5 Hz, 2H); 3.94 t (J =

7.5 Hz, 2H); 6.68 d (J = 2 Hz, 1H); 6.95 dd (J = 8.2 Hz, 1H); 7.33-7.54 m (7H); 7.63 d (J = 8 Hz, 2H); 7.69 d (J = 8 Hz, 1H).

Example 41

6- [[1- (4-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[1- (4-chlorophenyl) ) -2-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

D.C. 115-120 ° C

Example 42

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

65858 B1 acid

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

To a solution of 10 g of 1-chloro-3,4-dinitrobenzyl in 50 ml of ethanol was added 81 ml of o-toluidine and heated for 72 h counter-current. It was concentrated in vacuo and the residue was taken up in ethyl acetate and 2 N aqueous hydrochloric acid. The organic phase was extracted three more times with 2 N aqueous hydrochloric acid, dried over sodium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel.

1 H-NMR (CDCl ₃ ): δ = 2.28 ppm s (3H);

6.70 dd (J = 10.2 Hz, 1H); 6.80 d (J = 2 Hz, 1H);

7.22-7.40 m (4H); 8.18 d (J = 10 Hz, 1H); 9.40 s (breit) (1H).

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

To a solution of 1 g of sodium in 2 ml of methanol was added 1 g of 5-chloro-2-nitrophenyl-o-tolylamine and heated for 72 hours in reverse. Finally, it was cooled to 0 ° C and the crystalline product was sucked off with a suction filter.

1 H-NMR (CDCl 3): δ = 2.30 ppm s (3H);

3.72 s (3H); 6.19 d (J = 2 Hz, 1H); 6.32 dd (J = 10.2 Hz, 1H); 7.20-7.40 m (4H); 8.20 d (J = 10 Hz, 1H); 9.62 s (breit) (1H).

c) 6-methoxy-1- (2-methylphenyl) -2-phenyl-1H-benzimidazole is obtained by converting 5-methoxy-2-nitrophenyl-o-tolylamine according to the general prescription for work 1 and the final cyclization with triethylorthobenzoate according to the general prescription for work 3.

1 H-NMR (CDCl 3): δ = 1.93 ppm s (3H); 3.78 s (3H); 6.42 d (J = 2 Hz, 1H); 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 = 8 Hz, 1H).

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

6-Methoxy-1- (2-methylphenyl) -2-phenyl-1 N -benzimidazole was converted according to general prescription 6. The crude product was converted to 6-bromohexanoic acid methyl ester according to general prescription 8.

1 H-NMR (CDCl 3): δ = 1.43-1.58 ppm m (2H); 1.62-1.84 m (4H); 1.93 s (3H); 2.34 t (J =

7.5 Hz, 2H); 3.68 s (3H); 3,901 (J = 7.5 Hz, 2H);

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

Example 43

6 - [[1- (2-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting 6 - [[1- (2-methylphenyl) -2 methyl ester -phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 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-t-tolylamine

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

1 H-NMR (CDCl 3): δ-2.40 ppm s (3H);

6.72 dd (J = 10.2 Hz, 1H); 7.04-7.13 m (3H); 7.14 d (J = 2 Hz, 1H); 7.321 (J = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.52 s (breit) (1H).

b) 5-methoxy-2-nitrophenyl-t-tolylamine

To a solution of 9 g of sodium in 670 ml of methanol was added 39 g of 5-chloro-2-nitrophenyl-tololylamine and heated for 72 h counter-current. Finally, it was cooled to 0 ° C and the crystalline product was sucked off with a suction filter.

1 H-NMR (CDCl 3): δ = 2.40 ppm s (3H);

3.73 s (3H); 6.33 dd (J = 10.2 Hz, 1H); 6.58 d (J = 2 Hz, 1H); 7.03-7.15 m (3H); 7.311 (J = 10 Hz, 1H); 8.19 d (J = 10 Hz, 1H); 9.72 s (breit) (1H).

c) 6-methoxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole is obtained by converting 5-methoxy-2-nitrophenyl-t-tolylamine according to the general prescription for work 1 and the final cyclization with triethylorthobenzoate according to the general prescription for work 3.

1 H-NMR (CDCl 3): δ = 2.42 ppm s (3H); 3.81 s (3H); 6.69 d (J - 2 Hz, 1H); 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 - 8 Hz, 1H).

d) 6-hydroxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole is obtained by converting 6-methyl

65858 B1- 1- (3-methylphenyl) -2-phenyl-1H-benzimidazole according to general prescription 6.

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

6 - [[1- (3-Methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1- (3-methylphenyl) -2-phenyl -1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.44-1.58 ppm m (2H); 1.64-1.85 m (4H); 2.35t (J = 7.5 Hz, 2H);

2.40 s (3H); 3.68 s (3H); 3.95 t (J = 7.5 Hz, 2H);

6.70 d (J = 2 Hz, 1H); 6.96 dd (J = 8, 2 Hz, 1H); 7.10 d (J = 8 Hz, 1H); 7.16 s (breit) (2H); 7.25-

7.43 m (4H); 7.55 dd (J = 8.1 Hz, 2H); 7.77 d (J = 8 Hz, 1H).

Example 45

6 - ((1- (3-Methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hydroxy-1- (3-methylphenyl) -2-phenyl- 6-Bromohexanoic acid isopropyl ester 1H-benzimidazole according to general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.22 ppm d (J = 8 Hz, 6H); 1.44-1.56 m (2H, CH ₂ ); 1.64-1.84 m (4H, CH); 2.30 t (J = 7.5 Hz, 2H); 2.41 s (3H); 3.95 t (J = 7.5 Hz, 2H); 5.00 sp (J = 8 Hz, 1H);

6.68 d (J = 2 Hz, 1H); 6.96 dd (J = 8, 2 Hz, 1H); 7.10 d (J = 8 Hz, 1H); 7.14 s (breit) (1H); 7.25-

7.41 m (4H); 7.54 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8 Hz, 1H).

Example 46

6 - [[1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (3-methylphenyl) -2- methyl ester] Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general instructions for the product 9.

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

Example 47

6 - ((1- (3-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting 6 - [[1- (3-methylphenyl) methyl ester) ) -2-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.85 m (8H); 2.40 s (3H); 3.681 (J = 7.5 Hz, 2H); 3.961 (J = 7.5 Hz, 2H); 6.69 d (J = 1.5 Hz, 1H); 6.96 dd (J = 8, 1.5 Hz, 1H); 7.10 d (J = 8 Hz, 1H); 7.13 s (breit) (1H); 7.25-7.42 m (5H); 7.54 dd (J = 8, 1 Hz, 2H); 7.76 d (J = 8 Hz, 1H).

Example 48

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

a) 5-chloro-2-nitrophenyl-p-tolylamine was prepared analogously to 5-chloro-2-nitrophenyl-t-tolylamine from 1-chloro-3,4-dinitrobenzyl and p-toluidine. It is purified by crystallization.

Ή-NMR (CDCl): δ = 2.40 ppm s (3H);

6.70 dd (J = 10.2 Hz, 1H); 7.08 d (J = 2 Hz, 1H); 7.16 d (J = 10 Hz, 2H); 7.28 d (J = 10 Hz, 2H);

8.18 d (J = 10 Hz, 1H); 9.50 s (breit) (1H).

b) 5-methoxy-2-nitrophenyl-p-tolylamine is prepared analogously to 5-methoxy-2-nitrophenyl-t-tolylamine from 5-chloro-2-nitrophenyl-p-tolylamine and sodium methanolate.

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

c) 6-methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole is obtained by converting 5-methoxy-2-nitrophenyl-p-tolylamine according to the general prescription for operation 1 and final cyclization with triethylorthobenzoate according to the general prescription for work 3.

1 H-NMR (CDCl ₃ ): δ = 2.49 ppm s (3H);

3.80 s (3H); 6.69 d (J = 2 Hz, 1H); 6.97 dd (J = 8.2 Hz, 1H); 7.20 d (breit) (J = 8 Hz, 2H); 7.25-7.36 m (5H); 7.53 dd (J = 8, 1 Hz, 2H); 7.76 d (J = 8 Ηζ, ΙΗ).

d) 6-hydroxy-1- (4-methylphenyl) -2-phenyl1H-benzimidazole is obtained by converting 6-methane27

65858Bl-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole according to general prescription 6.

1 H-NMR (D ₆ -DMSO): delta = 2.40 ppm s (3H); 6.50 d (J = 2 Hz, 1H); 6.80 dd (J = 8.2 Hz, 1H); 7.28 d (J = 8 Hz, 2H); 7.32-7.43 m (5H); 7,467.52 m (2H); 7.56 d (J = 8 Hz, 1H); 9.28 s (breit) (1H).

6 - ((- 1- (4-methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1- (4-methylphenyl) -2 -phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to the general prescription has worked 8.

1 H-NMR (CDCl 3: delta = 1.44-1.58 ppm m (2H); 1.62-1.86 m (4H); 2.341 (J = 7.5 Hz, 2H); 2.48 s (3H); 3.68 s (3H); 3.941 (J = 7.5 Hz, 2H);

6.69 d (J = 2 Hz, 1H); 6.96 dd (J = 8, 2 Hz, 1H);

7.19 d (J = 8 Hz, 2H); 7.28-7.38 m (5H); 7.55 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8 Hz, 1H).

Example 49

6 - (((1- (4methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester) is obtained by conversion of 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H -benzimidazoles isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

1 H-NMR (CDCl 3: δ = 1.22 ppm d (J =

7.5 Hz, 6H); 1.44-1.56 m (2H); 1.62-1.85 m (4H); 2.301 (J = 7.5 Hz, 2H); 2.47 s (3H); 3.931 (J = 7.5 Hz, 2H); 5.01 sp (J = 7.5 Hz, 1H); 6.68 d (J = 2 Hz, 1H); 6.96 dd (J = 8, 2 Hz, 1H); 7.20 d (J = 8 Hz, 2H); 7.26-7.36 m (5H); 7.55 dd (J = 8, 1 Hz, 2H); 7.75 d (J = 8 Hz, 1H).

Example 50

6 - [(1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (4-methylphenyl) -2- methyl ester] Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 186-190 ° C

Example 51

6 - ((1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - ((1- (4-methylphenyl)) -2-Phenyl-6-yl] oxy] hexanoic acid according to general prescription 11.

1 H-NMR (CDCl ₃ ): δ = 1.38-1.80 m (8H); 2.47 s (3H); 3.651 (J = 7.5 Hz, 2H); 3.93 t (J = 7.5 Hz, 2H); 6.68 d (J = 2 Hz, 1H); 6.97 dd (J = 8.2 Hz, 1H); 7.18 d (J = 8 Hz, 2H); 7.24-7.37 m (5H); 7.54 dd (J = 8.1 Hz, 2H); 7.75 d (J = 8 Hz, 1H).

Example 52

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

a) 3- (3,4-dimethylphenyl) amino-4-nitrophenyl g 3-fluoro-4-nitrophenol and 6.9 g of 3,4-dimethylaniline were mixed and stirred for 2 h at 150 ° C. After cooling, it was dissolved in dichloromethane and extracted six times with 1N aqueous hydrochloric acid. The organic phase was discarded and the combined aqueous phases were extracted with chloroform. The combined extracts and the residue were chromatographed on silica gel.

1 H-NMR (CDCl ₃ / D ₆ -DMSO): delta 2.18 ppm s (6H); 6.13 dd (J = 8, 2 Hz, 1H); 6.36 d (J = 2 Hz, 1H); 6.90-7.00 m (2H); 7.09 d (J = 8 Hz, 1H); 7.93 d (J = 8 Hz, 1H); 9.50 s (breit) (1H);

10.19 s (breit) (1H).

b) 6- (3- (3,4-Dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3,4-dimethylphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription 8.

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

6 - ((1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester is obtained by converting 6- (3- (3,4-dimethylphenyl) amino methyl ester) -4-nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl ₃ ): δ = 1.44-1.56 ppm

65858 Bl m (2H); 1.62-1.84 m (4H); 2.30 s (3H); 2.331 (J =

7.5 Hz, 2H); 2.34 s (3H); 3.68 s (3H); 3.93 t (J =

7.5 Hz, 2H); 6.67 d (J = 2 Hz, 1H); 6.94 dd (J = 8, 2 Hz, 1H); 7.03 dd (J = 8, 1.5 Hz, 1H); 7.09 s (breit) (1H); 7.22-7.35 m (4H); 7.57 dd (J = 8, 1.5 Hz, 2H); 7.76 d (J = 8 Hz, 1H).

Example 53

6- [[1- (3,4-dimethylphenyl) -2-phenyl-1 H -benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - (((1- (3,4-dimethylphenyl) -) methyl ester 2-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. Mp 158-161 ° C

Example 54

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

a) 3- (3,5-dimethylphenyl) amino-4-nitropheniol

5.4 g of 3-fluoro-4-nitrophenyl and 3.4 ml of 3,5-dimethylaniline are combined and stirred for 6 hours at 120 ° C. After cooling, it was absorbed in ethyl acetate and water and extracted three times with 1N aqueous hydrochloric acid. The combined aqueous phases were dried over sodium sulfate, concentrated in vacuo and the residue crystallized.

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

b) 6- (3- (3,5-Dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3,5-dimethylphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.52 ppm m (2H); 1.60-1.80 m (4H); 2.301 (J = 7.5 Hz, 2H)

2.32 s (6H); 3.68 s (3H); 3,881 (J = 7.5 Hz, 2H); 6.30 dd (J = 8.2 Hz, 1H); 6.52 d (J = 2 Hz, 1H); 6.88 s (breit) (1H); 6.91 s (breit) (2H); 8.17 d (J = 8 Hz, 1H); 9.69 s (breit) (1H).

6- (3- (3,5-Dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 6- (3- (3,5-dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester according to the general prescription for work 2 and the final cyclization with triethylorthobenzoate according to the general prescription for work 3.

D.C. 124-126 ° C

Example 55

6 - ((1- (3,5-dimethylphenyl) -2-phenyl-1 H -benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6- (3- (3,5-dimethylphenyl) amino- 4-nitrophenyl] oxyhexanoic acid according to general prescription 9.

D.C. Mp 162-164 ° C

Example 56

6 - (((1- (3,5-Dimethyl-phenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester) is obtained by converting 6- (3- (3,5-dimethylphenyl) amino-4- nitrophenyl] oxyhexanoic acid with isopropanol according to the general prescription 10.

D.C. 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-nitrophenyl g 3-fluoro-4-nitrophenyl and 9.4 g m-anisidine were combined and stirred at 150 ° C for 2.5 h. After cooling, it was dissolved in dichloromethane and extracted three times with 1 N aqueous hydrochloric acid. The organic phase was dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 3.83 ppm s (3H); 6.30 dd (J = 10.2 Hz, 1H); 6.57 d (J = 2 Hz, 1H); 6.70-6.84 m (2H); 6.89 d (breit) (J = 10 Hz, 1H);

7.32 t (J = 10 Hz, 1H); 8.19 d (J = 10 Hz, 1H);

9.68 s (breit) (1H); 9.69 s (Breit).

b) 6- [3- (3-Methoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3-methoxyphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription for work 8.

1 H-NMR (CDCl ₃ ): δ = 1.42-1.58 ppm m (2H); 1.60-1.93 m (4H); 2,341 (J = 7.5 Hz, 2H);

3.68 s (3H); 3.80 s (3H); 4.03 t (J = 7.5 Hz, 2H);

6.32 dd (J = 10.2 Hz, 1H); 6.59 d (J = 2 Hz, 1H); 6.68-6.84 m (2H); 6.90 d (breit) (J = 8 Hz, 1H);

65858 Bl

7.32t (J = 8 Hz, 1H); 8.19 d (J = 10 Hz, 1H); 9.70 s (breit) (1H).

6 - [[1- (3-Methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- [3- (3-methoxyphenyl) amino-4 methyl ester -nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl ₃ ): δ = 1.44-1.58 ppmm (2H); 1.62-1.86 m (4H); 2.34 t (J = 7.5 Hz, 2H);

3.68 s (3H); 3.78 s (3H); 3.95 t (J = 7.5 Hz, 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 Hz, 1H); 7.56 dd (J = 8.2 Hz, 2H); 7.74 d (J = 8 Hz, 1H).

Example 58

6 - [[1- (3-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (3-methoxyphenyl) -2- methyl ester] Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 149-152 ° C

Example 59

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

a) 3- (methoxyphenyl) amino-4-nitrophenyl

0.16 g of 3-fluoro-4-nitrophenyl and 0.37 g of ranisidine are combined and stirred for 1.5 h at 150 ° C. After cooling, it was dissolved in dichloromethane, extracted twice with 1N aqueous hydrochloric acid and once with saturated sodium chloride solution. The organic phase was dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl ₃ / D ₆ -DMSO): delta = 3.57 ppm s (3H); 6.06 dd (J = 10.2 Hz, 1H); 6.18 d (J = 2 Hz, 1H); 6.77 d (J = 10 Hz, 2H); 7.03 d (J = 10 Hz, 2H); 7.89 d (J = 10 Hz, 1H); 9.40 s (breit) (1H);

9.80 s (Breit).

b) 6- [3- (4-Methoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (4-methoxyphenyl) amino-4-nitrophenol with 6-bromohexanoic acid methyl ester according to vol. because the instruction manual 8.

1 H-NMR (CDCl ₃ ): δ = 1.38-1.50 ppm m (2H); 1.60-1.80 m (4H); 2.33 t (J = 7.5 Hz, 2H); 3.67 s (3H); 3.85 t (J = 7.5 Hz, 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 = 10 Hz, 2H); 7.20 d (J = 10 Hz, 2H); 8.18 d (J = 10 Hz, 1H); 9.63 s (breit) (1H).

6 - [[1- (4-Methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 6- [3- (4-methoxyphenyl) amino- 4nitrophenyl] oxyhexanoic acid according to general operating requirement 1 and final cyclization with triethylorthobenzoate according to general operating instruction 3.

D.C. 98-102 ° C

Example 60

6 - [[1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (4-methoxyphenyl) -2- methyl ester] Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general operating instructions 9.

D.C. 160-165 ° C

Example 61

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

a) 3- (3,4-dimethoxyphenyl) amino-4-nitrophenyl g 3-fluoro-4-nitrophenyl and 8.8 g of 3,4-dimethoxyaniline were combined and stirred for 2 h at 150 ° C. After cooling, it was dissolved in dichloromethane and extracted twice with 1 N aqueous hydrochloric acid. The organic phase was extracted twice with chloroform and the combined chloroform extracts were dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (D ₆ -DMSO): delta = 3.75 ppm s (3H); 3.78 s (3H); 6.25 dd (J = 10.2 Hz, 1H); 6.35 d (J = 2 Hz, 1H); 6.88 dd (J = 8.1.5 Hz, 1H); 6.98 d (J = 1.5 Hz, 1H); 7.05 d (J = 8 Hz, 1H); 8.04 d (J = 10 Hz, 1H); 9.52 s (breit) (1H); 10.72 s (Breit).

b) 6- [3- (3,4-Dimethoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3,4-dimethoxyphenyl) amino-4-nitrophenol with methyl

65858 6-Bromohexanoic acid ester according to general prescription 8.

1 H-NMR (CDCl 3: δ = 1.40-1.52 ppm m (2H); 1.60-180 m (4H); 2.321 (J = 7.5 Hz, 2H);

3.68 s (3H); 3,851 (J = 7.5 Hz, 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 = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.68 s (breit) (1H).

6 - ((1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester is obtained by converting 6- (3- (3,4-dimethoxyphenyl) methyl ester) amino-4-nitrophenyl] oxyhexanoic acid according to general prescription for work 1 and final cyclization with triethylorthobenzoate according to general prescription for work 3.

D.C. 116-118 ° C

Example 62

6 - ((1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting the methyl ester to 6 - ([1- (3,4-dimethoxyphenyl) - 2-Phenyl1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general operating instructions 9.

D.C. 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

0.86 g of 3-fluoro-4-nitrophenol and 2.25 g of 3,4-methylenedioxyaniline are combined and stirred for 5 h at 120 ° C. The crude mixture was chromatographed on silica gel.

1 H-NMR (D ₆ -DMSO): delta = 6.02 ppm s (2H); 6.25 dd (J = 10.2 Hz, 1H); 6.33 d (J = 2 Hz, 1H); 6.72 dd (J = 8, 1.5 Hz, 1H); 6.87 d (J = 1.5 Hz, 1H); 7.05 d (J = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.52 s (breit) (1H).

b) 6- (3- (3,4-Methylenedioxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid ethyl ester is obtained by converting 3- (3,4methylenedioxyphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription 8.

bp 108-111 ° C

6 - ((1- (3,4-methylenedioxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- (3- (3, 4-methylenedioxyphenyl) amino-

4-nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl 3: δ = 1.43-1.55 ppm m (2H); 1.65-1.82 m (4H); 2.351 (J = 7.5 Hz, 2H);

3.68 s (3H); 3.95 t (J = 7.5 Hz, 2H); 6.10 s (2H); 6.65 d (J = 1.5 Hz, 1H); 6.72-6.83 m (2H); 6.90 d (J = 10 Hz, 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 = 10 Hz, 1H).

Example 64

6 - ((1- (3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting the methyl ester to 6 - ((1- (3 , 4-methylenedioxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 130 ° 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-nitrophenyl

3.7 g of 3-fluoro-4-nitrophenol and 4.76 g of 3,4,5 trimethoxyaniline are combined and stirred for 10 hours at 100 ° C. After cooling, it was absorbed in ethyl acetate and water and extracted three times with ethyl acetate. The combined organic phases were extracted three times with 1N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The product was digested with diisopropyl ether.

1 H-NMR (D ₆ -DMSO): delta = 3.70 ppm s (3H); 3.80 s (6H); 6.28 dd (J = 10.2 Hr, 1H); 6.53 d (J = 2 Hz, 1H); 6.70 s (2H); 8.05 d (J = 10 Hz, 1H); 9.50 s (breit) (1H); 10.71 s (Breit).

b) 6- [4-Nitro-3 - [(3,4-trimethoxyphenyl) amino] phenyl] oxyhexanoic acid methyl ester is obtained by conversion of 4-nitro-3 - [(3,4,5-trimethoxyphenyl) amino] phenol p

65858 B1 6-Bromohexanoic acid methyl ester according to general working order 8.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.53 ppm m (2H); 1.60-1.82 m (4H); 2.32 t (J = 7.5 Hz, 2H);

3.67 s (3H); 3.85 s (6H); 3.88 t (J = 7.5 Hz, 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 = 10 Hz, 1H);

9.68 s (breitX1H).

6 - [[2-Phenyl-1- (3,4,5 trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- [4-nitro-3- methyl ester [(3,4,5-trimethoxyphenyl) amino] phenyl] oxyhexanoic acid according to general prescription for work 1 and final cyclization with triethylorthobenzoate according to general prescription for work 3.

D.C. 128-130 ° C

Example 66

6- [[1-Phenyl-1- (3,4,5-trimethoxyphenyl) 1 H -benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2-phenyl-1 - ( 3,4,5-trimethoxyphenyl) 1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general prescription 9.

D.C. 198-201 ° C

Example 67

6 - [[2-Phenyl-1 (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6 - [[2-phenyl-1- - (3, 4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid with isopropanol according to general prescription 10.

D.C. 98-101 ° C

Example 68

6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl] oxy] hexanoic acid methyl ester

a) HH-dimethyl-N- (5-chloro-2-nitrophenyl) benzene-1,4-diamine was prepared analogously to 5-chloro-2-nitrophenyl-t-tolylaminot 1-chloro-3,4-dinitrobenzene and Ν , N-dimethyl-p-phenylenediamine.

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

b) ND-dimethyl-N- (5-methoxy-2-nitrophenyl) benzene-1,4-diamine

24.9 g of N, N-dimethyl-N- (5-chloro-2-nitro phenyl) benzene-1,4-diamine were added to a solution of 8 g of sodium in 200 ml of methanol and the mixture was heated in an autoclave for 9 h to a temperature of 120 ° C. After cooling, the crystalline product is suction filtered off.

1 H-NMR (CDCl ₃ ): δ = 3.00 ppm s (6H);

3.70 s (3H); 6.25 dd (J = 10.2 Hz, 1H); 6.34 d (J = 2 Hz, 1H); 6.78 d (J = 10 Hz, 2H); 7.14 d (J = 10 Hz, 2H); 8.16 d (J = 10 Hz, 1H); 9.67 s (brelt) (1H).

c) 6-methoxy-1- [4- (1H-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole is obtained by converting N, N-dimethyl-L- (5-methoxy-2-nitrophenyl) benzene -1,4diamine according to general rule 1, final conversion of crude diamine with trimethylorthobenzoate according to general rule 3 and subsequent heating of the crude product with 6N aqueous hydrochloric acid for 1 h counter-current. After alkalisation of the reaction mixture with aqueous sodium hydroxide, it was extracted with ethyl acetate, dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl 3: δ = 3.04 ppm s (6H);

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

d) 6-hydroxy-1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole is obtained by converting 6-methoxy-1- [4- (H, N-dimethylamino) phenyl ] -2-Phenyl-1H-benzimidazole according to general prescription 6.

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

6 - [[1- [4- (N 4 -Dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester was obtained by conversion of 6-hydroxy-1- [4 (M, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.43-1.57 ppm m (2H); 1.64-1.85 m (4H); 2.33 t (J = 7.5 Hz, 2H); 3.05 s (6H); 3.67 s (3H); 3.93 t (J = 7, 5 Hz,

65858 Bl

2H); 6.65 d (J = 2 Hz, 1H); 6.76 d (J = 10 Hz, 2H);

6.93 dd (J = 10.2 Hz, 1H); 7.14 d (J = 10 Hz, 2H); 7.23-7.27 m (3H); 7.62 dd (J = 10, 1.5 Hz, 2H); 7.74 d (J = 10 Hz, 1H).

Example 69

6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting the methyl ester to 6 - [[1 - [ 4- (N, N-Dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 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 was prepared analogously to 5-chloro-2-nitrophenyl-t-tolylamine from 1-chloro-3,4-dinitrobenzyl and 4-biphenylamine. It is purified by chromatography on silica gel.

1 H-NMR (CDCl 3: delta = 6.76 dd (J = 10, 2 Hz, 1H); 7.26 d (J = 2 Hz, 1H); 7.35 d (J = 8 Hz, 1H); 7.32-7.52 m ( 4H); 7.60-7.72 m (4H); 8.19 d (J = 10 Hz, 1H); 9.60 s (breit) (1H).

b) 5-methoxy-2-nitrophenyl-4-biphenylamine was prepared analogously to 5-methoxy-2-nitrophenyl-t-4-biphenylamine and sodium methanolate.

D.C. 150-154 ° C

b) 1- (4-biphenyl) -6-methoxy-2-phenyl-1 H -benzimidazole is obtained by converting

5-methoxy-2-nitrophenyl-4-biphenylamine according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

D.C. 140-144 ° C

c) 1- (4-Biphenyl) -6-hydroxy-2-phenyl-1H-benzimidazole is prepared by converting 1- (4-biphenyl) -6-methoxy-2-phenyl-1H-benzimidazole according to general prescription 6 .

D.C. 312 ° C

6 - [[1- (4-Biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 1- (4-biphenyl) -6-hydroxy-2- phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 106-108 ° C

Example 71

6 - [[1- (4-biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (4-biphenyl) -2 methyl ester -phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.35-1.78 ppm m (6H); 2.201 (J = 7.5 Hz, 2H); 3.96 m (2H);

6.72 d (J = 2 Hz, 1H); 6.97 dd (J = 10.2 Hz, 1H); 7.32-7.58 m (10H); 7.69 d (J = 10 Hz, 1H); 7.80 d (J = 8 Hz, 2H); 7.89 d (J = 10 Hz, 2H).

Example 72

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

a) 3- (2-naphthylamino) -4-nitrophenyl g 3-fluoro-4-nitrophenyl and 8.2 g 2-naphthylamine are combined and stirred for 8 hours at 180 ° C. The crude mixture was absorbed in chloroform and washed with 2N hydrochloric acid. The organic phase was dried over sodium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (D ₆ -DMSO): delta = 6.02 ppm s (2H); 6.25 dd (J = 10.2 Hz, 1H); 6.33 d (J = 2 Hz, 1H); 6.72 dd (J = 8, 1.5 Hz, 1H); 6.87 d (J = 1.5 Hz, 1H); 7.05 d (J = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.52 s (breit) (1H).

b) 6- [3- (2-Naphthyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (2-naphthylamino) -4-nitrophenol with 6-bromohexanoic acid methyl ester according to the general reg. 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-nitropheniol

5.4 g of 3-fluoro-4-nitrophenyl and 3.4 ml of 3,5-dimethylaniline are combined and stirred for 6 hours at 120 ° C. After cooling, it was absorbed in ethyl acetate and water and extracted three times with 1N aqueous hydrochloric acid. The mixed aqueous phases are

65858 B1 was dried over sodium sulfate, concentrated in vacuo and the residue crystallized.

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

b) 6- (3- (3,5-Dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3,5-dimethylphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.52 ppm m (2H); 1.60-1.80 m (4H); 2.301 (J = 7, 5 Hz, 2H) 2.32 s (6H); 3.68 s (3H); 3.88 t (J = 7.5 Hz, 2H); 6.30 dd (J = 8.2 Hz, 1H); 6.52 d (J = 2 Hz, 1H); 6.88 s (breit) (1H); 6.91 s (breit) (2H); 8.17 d (J = 8 Hz, 1H); 9.69 s (breit) (1H).

6- (3- (3,5-Dimethylphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 6- (3- (3,5-dimethylphenyl) amino-4-nitrophenyl] oxyhexanoyl ester acid according to general prescription 2 and final cyclization with triethylorthobenzoate according to general prescription 3.

D.C. 124-126 ° C

Example 55

6 - ((1- (3,5-dimethylphenyl) -2-phenyl-1 H -benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting 6- (3- (3,5-dimethylphenyl) amino- 4-nitrophenyl] oxyhexanoic acid according to general prescription 9.

D.C. Mp 162-164 ° C

Example 56

6 - ((1- (3,5-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6- (3- (3,5-dimethylphenyl) amino-4-nitrophenyl) ] oxyhexanoic acid with isopropanol according to the general prescription has worked 10.

D.C. 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-nitrophenyl g 3-fluoro-4-nitrophenyl and 9.4 g m-anisidine were combined and stirred at 150 ° C for 2.5 h. After cooling, it was dissolved in dichloromethane and extracted three times with 1 N aqueous hydrochloric acid. The organic phase was dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

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

9.68 s (breit) (1H); 9.69 s (Breit).

b) 6- [3- (3-Methoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3-methoxyphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription for work 8.

1 H-NMR (CDCl ₃ ): δ = 1.42-1.58 ppm m (2H); 1.60-1.93 m (4H); 2,341 (J = 7.5 Hz, 2H); 3.68 s (3H); 3.80 s (3H); 4.03 t (J = 7.5 Hz, 2H); 6.32 dd (J = 10.2 Hz, 1H); 6.59 d (J = 2 Hz, 1H); 6.68-6.84 m (2H); 6.90 d (breit) (J = 8 Hz, 1H); 7.321 (J = 8 Hz, 1H); 8.19 d (J = 10 Hz, 1H);

9.70 s (breit) (1H).

6 - [[1- (3-Methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 6- [3- (3-methoxyphenyl) amino- 4-nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl ₃ ): δ = 1.44-1.58 ppm m (2H); 1.62-1.86 m (4H); 2.34 t (J = 7.5 Hz, 2H); 3.68 s (3H); 3.78 s (3H); 3.95 t (J = 7.5 Hz, 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); 7,277.36 m (3H); 7,401 (J = 8 Hz, 1H); 7.56 dd (J = 8, 2 Hz, 2H); 7.74 d (J = 8 Hz, 1H).

Example 58

6 - ((1- (3-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (3-methoxyphenyl) -2- methyl ester) phenyl-1H

65858 B1 benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 149-152 ° C

Example 59

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

a) 3- (methoxyphenyl) amino-4-nitrophenyl

0.16 g of 3-fluoro-4-nitrophenyl and 0.37 g of ranisidine are combined and stirred for 1.5 h at 150 ° C. After cooling, it was dissolved in dichloromethane, extracted twice with 1N aqueous hydrochloric acid and once with saturated sodium chloride solution. The organic phase was dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl ₃ / D ₆ -DMSO): delta = 3.57 ppm s (3H); 6.06 dd (J = 10.2 Hz, 1H); 6.18 d (J = 2 Hz, 1H); 6.77 d (J = 10 Hz, 2H); 7.03 d (J = 10 Hz, 2H); 7.89 d (J = 10 Hz, 1H); 9.40 s (breit) (1H);

9.80 s (Breit).

b) 6- [3- (4-Methoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (4-methoxyphenyl) amino-4-nitrophenol with 6-bromohexanoic acid methyl ester according to the general operating instructions 8.

1 H-NMR (CDCl ₃ ): δ = 1.38-1.50 ppm m (2H); 1.60-1.80 m (4H); 2.331 (J = 7.5 Hz, 2H); 3.67 s (3H); 3.85 t (J = 7.5 Hz, 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 = 10 Hz, 2H); 7.20 d (J = 10 Hz, 2H); 8.18 d (J = 10 Hz, 1H); 9.63 s (breit) (1H).

6 - [[1- (4-Methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- [3- (4-methoxyphenyl) amino methyl ester -4-nitrophenyl] oxyhexanoic acid according to general instruction 1 and final cyclization with triethylorthobenzoate according to general instruction 3.

D.C. 98-102 ° C

Example 60

6- [[1- (4-Methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (4-methoxyphenyl) -2 methyl ester -phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general operating instructions 9.

D.C. 160-165 ° C

Example 61

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

a) 3- (3,4-dimethoxyphenyl) amino-4-nitrophenyl g 3-fluoro-4-nitrophenyl and 8.8 g of 3,4-dimethoxyaniline were combined and stirred for 2 h at 150 ° C. After cooling, it was dissolved in dichloromethane and extracted twice with 1N aqueous hydrochloric acid. The organic phase was extracted twice with chloroform and the combined chloroform extracts were dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (D ₆ -DMSO): delta = 3.75 ppm s (3H); 3.78 s (3H); 6.25 dd (J = 10.2 Hz, 1H); 6.35 d (J = 2 Hz, 1H); 6.88 dd (J = 8.1.5 Hz, 1H); 6.98 d (J = 1.5 Hz, 1H); 7.05 d (J = 8 Hz, 1H); 8.04 d (J = 10 Hz, 1H); 9.52 s (breit) (1H); 10.72 s (Breit).

b) 6- (3- (3,4-Dimethoxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is obtained by converting 3- (3,4-dimethoxyphenyl) amino-4-nitrophenol with 6-bromohexanoic acid methyl ester according to the general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.52 ppm m (2H); 1.60-180 m (4H); 2,321 (J = 7.5 Hz, 2H);

3.68 s (3H); 3,851 (J = 7.5 Hz, 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 = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.68 s (breit) (1H).

6 - ((1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- (3- (3,4-dimethoxyphenyl) amino methyl ester) -4-nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

D.C. 116-118 ° C

Example 62

6 - ((1- (3,4-dimethoxyphenyl) -2-phenyl-1 H -benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting 6 - (((1- (3,4-dimethoxyphenyl) -) methyl ester) 2-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

65858 Bl according to the general operating instructions 9.

D.C. 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

0.86 g of 3-fluoro-4-nitrophenol and 2.25 g of 3,4-methylenedioxyaniline are combined and stirred for 5 h at 120 ° C. The crude mixture was chromatographed on silica gel.

1 H-NMR (D ₆ -DMSO): delta = 6.02 ppm s (2H); 6.25 dd (J = 10.2 Hz, 1H); 6.33 d (J = 2 Hz, 1H); 6.72 dd (J = 8, 1.5 Hz, 1H); 6.87 d (J = 1.5 Hz, 1H); 7.05 d (J = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.52 s (breit) (1H).

b) 6- (3- (3,4-Methylenedioxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid ethyl ester is obtained by converting 3- (3,4methylenedioxyphenyl) amino-4-nitrophenyl with 6-bromohexanoic acid methyl ester according to the general prescription 8.

bp 108-111 ° C

6 - ((1- (3,4-methylenedioxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- (3- (3, 4-methylenedioxyphenyl) amino-4-nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl ₃ ): δ = 1.43-1.55 ppm m (2H); 1.65-1.82 m (4H); 2.35 t (J = 7.5 Hz, 2H);

3.68 s (3H); 3.95 t (J = 7.5 Hz, 2H); 6.10 s (2H);

6.65 d (J = 1.5 Hz, 1H); 6.72-6.83 m (2H); 6.90 d (J = 10 Hz, 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 = 10 Hz, 1H).

Example 64

6 - ((1- (3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting the methyl ester to 6 - ((1- (3 , 4-methylenedioxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 130 ° 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-nitrophenyl

3.7 g of 3-fluoro-4-nitrophenol and 4.76 g of 3,4,5 trimethoxyaniline are combined and stirred for 10 hours at 100 ° C. After cooling, it was absorbed in ethyl acetate and water and extracted three times with ethyl acetate. The combined organic phases were extracted three times with 1N aqueous hydrochloric acid and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The product was digested with diisopropyl ether.

1 H-NMR (D ₆ -DMSO): delta = 3.70 ppm s (3H); 3.80 s (6H); 6.28 dd (J = 10.2 Hr, 1H); 6.53 d (J = 2 Hz, 1H); 6.70 s (2H); 8.05 d (J = 10 Hz, 1H); 9.50 s (breit) (1H); 10.71 s (Breit).

b) 6- [4-Nitro-3 - [(3,4-trimethoxyphenyl) amino] phenyl] oxyhexanoic acid methyl ester is obtained by converting 4-nitro-3 - [(3,4,5-trimethoxyphenyl) amino] phenol to methyl 6-Bromohexanoic acid ester according to the general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.53 ppm m (2H); 1.60-1.82 m (4H); 2.32 t (J = 7.5 Hz, 2H); 3.67 s (3H); 3.85 s (6H); 3,881 (J = 7.5 Hz, 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 = 10 Hz, 1H); 9.68 s (breit) (1H).

6 - [(2-Phenyl-1- (3,4,5 trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- [4-nitro-3 methyl ester - [(3,4,5-trimethoxyphenyl) amino] phenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

D.C. 128-130 ° C

Example 66

6 - ((1-Phenyl-1- (3,4,5-trimethoxyphenyl) 1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting 6 - ([2-phenyl-1- methyl ester) (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general pres

65858 Bl and 9.

D.C. 198-201 ° C

Example 67

6 - [[2-Phenyl-1 (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6 - [[2-phenyl-1- (3 , 4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid with isopropanol according to general prescription 10.

D.C. 98-101 ° C

Example 68

6 - [[1- [4- (ND-Dimethylamino) phenyl] -2-phenyl] oxy] hexanoic acid methyl ester

a) N-dimethyl-N- (5-chloro-2-nitrophenyl) benzene-1,4-diamine was prepared analogously to 5-chloro-2-nitrophenyl-t-tolylamine from 1-chloro-3,4-dinitrobenzene and N, N-dimethyl-p-phenylenediamine.

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

b) N-dimethyl-N '- (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 in an autoclave for 9 h to temperature. 120 ° C. After cooling, the crystalline product is suction filtered off.

1 H-NMR (CDCl ₃ ): δ = 3.00 ppm s (6H);

3.70 s (3H); 6.25 dd (J = 10.2 Hz, 1H); 6.34 d (J = 2 Hz, 1H); 6.78 d (J = 10 Hz, 2H); 7.14 d (J = 10 Hz, 2H); 8.16 d (J = 10 Hz, 1H); 9.67 s (breit) (1H).

c) 6-Methoxy-1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazole is obtained by converting N, N-dimethyl-N- (5-methoxy-2-nitrophenyl) benzene-1,4diamine according to general prescription for job 1, final conversion of crude diamine with trimethylorthobenzoate according to general prescription for work 3 and subsequent heating of the crude product with 6N aqueous hydrochloric acid for 1 h counter-current. After alkalisation of the reaction mixture with aqueous sodium hydroxide, it was extracted with ethyl acetate, dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl ₃ ): δ = 3.04 ppm s (6H);

3.80 s (3H); 6.68 d (J = 2 Hz, 1H); 6.78 d (J = 10

Hz, 2H); 6.95 dd (J = 10.2 Hz, 1H); 7.17 d (J = 10 Hz, 2H); 7.25-7.33 m (3H); 7.56-7.64 m (2H); 7.74 d (J = 10 Hz, 1H).

d) 6-hydroxy-1- [4- (N, N-β-β-amino) phenyl] -2-phenyl-1H-benzimidazole is obtained by conversion of 6-methoxy-1- [4- (N-dimethylamino) phenyl] - 2-Phenyl-1H-benzimidazole according to general prescription 6.

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

6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1- [4 (N, dimethylamino) phenyl] -2-phenyl-

H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.43-1.57 ppm m (2H); 1.64-1.85 m (4H); 2.331 (J = 7.5 Hz, 2H); 3.05 s (6H); 3.67 s (3H); 3.93 t (J = 7., 5 Hz, 2H);

6.65 d (J = 2 Hz, 1H); 6.76 d (J = 10 Hz, 2H); 6.93 dd (J = 10.2 Hz, 1H); 7.14 d (J = 10 Hz, 2H); 7.23-7.27 m (3H); 7.62 dd (J = 10, 1.5 Hz, 2H); 7.74 d (J = 10 Hz, 1H).

Example 69

6 - [[1- [4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting the methyl ester to 6 - [[1 - [ 4- (N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 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 was prepared analogously to 5-chloro-2-nitrophenyl-t-tolylamine from 1-chloro-3,4-dinitrobenzyl and 4-biphenylamine. It is purified by chromatography on silica gel.

1 H-NMR (CDCl ₃ ): delta = 6.76 dd (J = 10,

Hz, 1H); 7.26 d (J = 2 Hz, 1H); 7.35 d (J = 8 Hz,

65858 Bl

1H); 7.32-7.52 m (4H); 7.60-7.72 m (4H); 8.19 d (J = 10 Hz, 1H); 9.60 s (breit) (1H).

b) 5-methoxy-2-nitrophenyl-4-biphenylamine was prepared analogously to 5-methoxy-2-nitrophenyl-t-4-biphenylamine and sodium methanolate.

D.C. 150-154 ° C

b) 1- (4-Biphenyl) -6-methoxy-2-phenyl-1 H -benzimidazole is obtained by converting 5-methoxy-2-nitrophenyl-4-biphenylamine according to the general prescription for work 1 and final cyclization with triethylorthobenzoate according to the general prescription for work 3.

D.C. 140-144 ° C

c) 1- (4-biphenyl) -6-hydroxy-2-phenyl-1H-benzimidazole is prepared by converting 1- (4-biphenyl) -6-methoxy-2-phenyl-1H-benzimidazole according to the general prescription of operation 6.

D.C. 312 ° C

6 - [[1- (4-Biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 1- (4-biphenyl) -6-hydroxy-2-phenyl- 6-Bromohexanoic acid 1H-benzimidazole methyl ester according to general prescription 8.

D.C. 106-108 ° C

Example 71

6 - [[1- (4-biphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (4-biphenyl) -2- methyl ester Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.35-1.78 ppm m (6H); 2.20t (J = 7.5 Hz, 2H); 3.96 m (2H); 6.72 d (J = 2 Hz, 1H); 6.97 dd (J = 10.2 Hz, 1H); 7.32-7.58 m (10H); 7.69 d (J = 10 Hz, 1H); 7.80 d (J = 8 Hz, 2H); 7.89 d (J = 10 Hz, 2H).

Example 72

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

a) 3- (2-naphthylamino) -4-nitrophenyl g 3-fluoro-4-nitrophenyl and 8.2 g 2-naphthylamine were combined and stirred for 8 hours at 180 ° C. The crude mixture was absorbed in chloroform and washed with 2N hydrochloric acid. The organic phase was dried over sodium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (D ₆ -DMSO): delta = 6.02 ppm s (2H); 6.25 dd (J = 10.2 Hz, 1H); 6.33 d (J = 2 Hz, 1H); 6.72 dd (J = 8.1.5 Hz, 1H); 6.87 d (J = 1.5 Hz, 1H); 7.05 d (J = 10 Hz, 1H); 8.18 d (J = 10 Hz, 1H); 9.52 s (breit) (1H).

b) 6- [3- (2-Naphthyl) amino-4-nitrophenyl] oxyhexanoic acid methyl ester is prepared by converting 3- (2-naphthylamino) -4-nitrophenol with 6-bromohexanoic acid methyl ester according to the general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 1.35-1.49 ppm m (2H); 1.60-1.80 m (4H); 2.30 t (J = 7.5 Hz, 2H); 3.64 s (3H); 3.841 (J = 7.5 Hz, 2H); 6.35 dd (J = 10.2 Hz, 1H); 6.62 d (J = 2 Hz, 1H); 7.43 dd (J = 10.2 Hz, 1H); 7.48-7.57 m (2H); 7.75 d (J = 2 Hz, 1H); 7.78-7.90 m (2H); 7.91 d (J = 10 Hz, 1H); 8.21 d (J = 10 Hz, 1H); 9.92 s (breit) (1H).

6 - [[1- (2-Naphthyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 6- [3- (2-naphthylamine) methyl ester - 4-nitrophenyl] oxyhexanoic acid according to general operating instructions 1 and final cyclization with triethylorthobenzoate according to general operating instructions 3.

D.C. 111-114 ° C

Example 73

6 - [[1- (2-naphthyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1- (2-naphthyl) -2 methyl ester -phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 170-175 ° C

Example 74

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

2.17 g of 3-fluoro-4-nitrophenyl and 5 g of 2-aminofluorone are combined and stirred for 9 hours at 140 ° C. The crude mixture was absorbed in ethyl acetate and water and washed with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed three times with 2N aqueous hydrochloric acid and once with saturated solution.

65858 B1 of sodium chloride, dried over sodium sulfate was concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (D ₆ -DMSO): delta - 3.96 ppm s (2H); 6.30 dd (J = 10.2 Hz, 1H); 6.52 d (J = 2 Hz, 1H); 7.28-7.45 m (3H); 7.57 s (breit) (1H); 7.60 d (J = 8 Hz, 1H); 7.92 d (J = 8 Hz, 1H); 7.98 d (J = 8 Hz, 1H); 8.10 d (J = 10 Hz, 1H); 9.70 s (1H);

10.80 s (breit) (1H).

b) 6- [3- (2fluorenylamino) -4-nitrophenyl] oxyhexanoic acid methyl ester is prepared by converting 3- (2fluorenylamino) -4-nitrophenyl with 6-bromohexanoic acid methyl ester according to general operating instructions 8.

1 H-NMR (CDCl ₃ ): δ = 1.38-1.50 ppm m (2H); 1.58-1.80 m (4H); 2.301 (J = 7.5 Hz, 2H);

3.65 s (3H); 3.841 (J = 7.5 Hz, 2H); 3.95 s (2H); 6.31 dd (J = 10.2 Hz, 1H); 6.53 d (J = 2 Hz, 1H); 7.331 (J = 8 Hz, 2H); 7.421 (J = 8 Hz, 1H); 7.47 s (1H); 7.58 d (J = 8 Hz, 1H); 7.80 d (J = 8 Hz, 1H); 7.83 d (J = 8 Hz, 1H); 8.21 d (J = 10 Hz, 1H); 9.87 s (breit) (1H).

6 - [[1- (2-Fluorenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- [3- (2-fluorenyl) amino) methyl ester - 4-nitrophenyl] oxyhexanoic acid according to general prescription 1 and final cyclization with triethylorthobenzoate according to general prescription 3.

D.C. 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

9.7 ml of 3- (trifluoromethyl) benzonitrile were dissolved in 12 ml of ethanol and the solution was saturated with hydrogen chloride gas when cooled in an ice bath. After 72 h, the precipitated product was sucked off with a suction filter. The product was washed with diethyl ether.

D.C. 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 for 24 hours at 140 ° C. After cooling, it was absorbed in ethyl acetate and extracted with 2 N aqueous strong acid. The organic phase was dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

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

c) 4-Methoxy-N ² -phenyl-o-phenylenediamine is prepared by converting 5-methoxy-2-nitrophenyldiphenylamine according to general prescription 1.

1 H-NMR (CDCl ₃ ): δ = 3.42 ppm s (breit) (2H); 3.72 s (3H); 5.33 s (breit) (1H); 6.56 dd (J = 10.2 Hz, 1H); 6.76 d (J = 10 Hz, 1H); 6.79 d (J = 2 Hz, 1H); 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 is obtained by converting 4-methoxy-b1 ^2- phenyl-o-phenylenediamine with ethyl (3-trifluoromethyl) benzimidahydrochloride according to the general prescription 4.

D.C. 138-140 ° C

e) 6-hydroxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole is obtained by converting 6-methoxy-1-phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazole according to general prescription for work 7.

1 H-NMR (D ₆ -DMSO): delta = 6.60 ppm d (J = 2 Hz, 1H); 6-99 dd (J = 10.2 Hz, 1H); 7,507.89 m (10H).

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1-phenyl-2- [3 - (Trifluoromethyl) phenyl] -1H-benzimidazole with 6-bromohexanoic acid methyl ester according to the general prescription 8.

D.C. 68-70 ° C

Example 76

6 - [[1-Phenyl-2- [3 (trifluoromethyl) phenyl] -1H-benzimide azol-6yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hydroxy-1-phenyl-2- [3 - (Trifluoromethyl) phenyl] -1H-benzimidazole with isopropyl ester of 6-bromine

65858 B1 hexanoic acid according to general prescription 8.

D.C. 96-98 ° C

Example 77

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] 1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1-phenyl-2- [3-methyl methyl] - (Trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.38-1.80 ppm m (6H); 2.27 t (J = 7.5 Hz, 2H); 3.98 t (J =

7.5 Liz, 2H); 6.70 d (J = 2 Hz, 1H); 7.02 dd (J = 10.2 Hz, 1H); 7.48-7.88 m (9H); 7.77 d (J = 10 Hz, 1H); 11.94 s (breit) (1H).

Example 78

6 - [[1-Phenyl-2- [3- (trifluoromethyl) phenyl] 1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[1-phenyl- 2- [3- (Trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general working order 11.

= 7.5 Hz, 2H); 6.69 d (J = 2 Hz, 1H); 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 (breit) (J = 8 Hz, 1H); 7.78 d (J = 10 Hz, 1H); 7.8: s (breit) (1H).

Example 79

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

a) 2- (3-Chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole was obtained by converting 4-methoxy-N-phenyl-o-phenylenediamine with ethyl 3-chlorobenzimidate hydrochloride (prepared by: De Wolfe und Augustine; J. Org Chem .; 30; 699) according to general prescription 4.

D.C. 149-151 ° C

b) 2- (3-Chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole is prepared by converting 2- (3-chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole according to general prescription 7.

D.C. 199-202 ° C

6 - [[2- (3-Chlorophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 2- (3 chlorophenyl) -6-hydroxy-1-phenyl- 1 H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 69-72 ° C

Example 80

6 - [[2- (3-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by converting 2- (3-chlorophenyl) -6-hydroxy-1-phenyl -1 H-benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 98-100 ° C

Example 81

6 - [[2- (3-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2- (3-chlorophenyl) -1 methyl ester -phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 137-140 ° C

Example 82

6 - [[2- (3-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[2- (3-chlorophenyl) -1-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.70 ppm m (6H); 1.75-1.86 m (2H); 3.67 t (J = 7.5 Hz, 2H); 3.93 t (J = 7.5 Hz, 2H); 6.69 d (J = 2 Hz, 1H); 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 = 10 Hz, 1H).

Example 83

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

a) Ethyl 4-chlorobenzimidate hydrochloride g 4-chlorobenzonitrile was suspended in 12 ml ethanol and dissolved by the addition of diethyl ether. When cooled in an ice bath, it is saturated with hydrogen chloride gas. After 72 h, the precipitated product was suction filtered off with suction. The product was washed with diethyl ether.

D.C. 173-174 ° C (dec.)

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

65858 B1 are prepared by converting 4-methoxy-L-phenyl-o-phenylenediamine with ethyl-4-benzimidate hydrochloride according to general operating instructions 4.

D.C. Mp 162-164 ° C

B) 2- (4-Chlorophenyl) -6-hydroxy-1-phenyl-1H-benzimidazole is prepared by converting 2- (4-chlorophenyl) -6-methoxy-1-phenyl-1H-benzimidazole according to general prescription 7.

D.C. Mp 246-250 ° C

6 - [[2- (4-Chlorophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 2- (4-chlorophenyl) -6-hydroxy-1-phenyl-1H -benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 86-87 ° C

Example 84

6 - [[2- (4-Chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by converting 2- (4-chlorophenyl) -6-hydroxy-1-phenyl-1H- benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 124-126 ° C

Example 85

6 - [[2- (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2- (4-chlorophenyl) -1- Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.35-1.48 ppm m (2H); 1.50-1.62 m (2H); 1.64-1.77 m (2H); 2.23 t (J = 7.5 Hz, 2H); 3.911 (J = 7.5 Hz, 2H); 6.64 cl (J = 2 Hz, 1H); 6.96 dd (J = 10.2 Hz, 1H); 7.38-7.50 m (6H); 7.52-7.65 m (3H); 7.70 d (J = 10 Hz, 1H).

Example 86

6 - [[2- (4-chlorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[2- (4-chlorophenyl) ) -1-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

1 H-NMR (CDCl 3: δ = 1.38-1.68 ppm m (6H); 1.74-1.85 m (2H); 3.671 (breit) (J = 7.5

Hz, 2H); 3.941 (J = 7.5 Hz, 2H); 6.68 d (J = 2 Hz, 1H); 6.98 dd (J = 10, 2 Hz, 1 HJ; 7.22-7.35 m (5H); 7.47 d (J = 8 Hz; 2H); 7.49-7.59 m (2H); 7.73 d (J = 10 Hz, 1H) .

Example 87

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

a) 6-Methoxy-2- (3-methylphenyl) -phenyl-1 H -benzimidazole was prepared by converting 4-methoxy-N-phenyl-o-phenylenediamine with ethyl 3-methylbenzimidate hydrochloride (obtained by: DeWolfe und Augustune; J. Org Chem .; 30; 699) according to general prescription 4.

D.C. Mp 156-158 ° C

b) 6-Hydroxy-2- (3-methylphenyl) -1-phenyl-1H-benzimidazole is prepared by converting 6-methoxy-2- (3-methylphenyl) -1-phenyl-1H-benzimidazole according to general prescription 7.

1 H-NMR (D ₆ -DMSO): delta = 2.23 ppm s (3H); 6.52 d (J = 2 Hz, 1H); 6.80 dd (J = 10.2 Hz, 1H); 7.18 s (breit) (3H); 7.35-7.52 m (3H); 7,507.83 m (4H); 9.28 s (breit) (1H).

(breit) = (wide)

6 - [[2- (3-Methylphenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-2- (3-methylphenyl) -1- phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to the general prescription 8.

D.C. 82-84 ° C

Example 88

6 - [[2- (3methoxyphenyl) -1-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid isopropyl ester is obtained by converting 6-hydroxy-2- (3-methylphenyl) -1phenyl-1H-benzimidazole with isopropyl ester of 6-bromohexanoic acid according to the general prescription of work 8.

1 H-NMR (CDCl ₃ ): δ = 1.22 ppm d (J =

7.5 Hz, 6H); 1.38-1.56 m (2H); 1.62-1.85 m (4H); 2.301 (J = 7.5 Hz, 2H); 2.30 s (3H); 3.931 (J = 7.5 Hz, 2H); 5.00 sp (J = 7.5 Hz, 1H); 6.68 d (J = 2 Hz, 1H); 6.95 dd (J = 10.2 Hz, 1H); 7.13 s (breit) (3H); 7.31 dd (J = 8, 2 Hz, 2H); 7.42-7.57 m (4H); 7.76 d (J = 10 Hz, 1H).

Example 89

65858 Bl

6 - [[2- (3-methoxyphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid are obtained by converting methyl ester to 6 - [[2- (3-methylphenyl) methyl ester] 1-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to the general prescription worked 9.

1 H-NMR (D ₆ -DMSO): delta = 1.35-1.49 ppm m (2H); 1.50-1.63 m (2H); 1.64-1.78 m (2H); 2.221 (J = 7.5 Hz, 2H); 2.24 s (3H); 3.921 (J = 7.5 Hz, 2H); 6.62 d (J = 2 Hz, 1H); 6.95 dd (J = 10.2 Hz, 1H); 7.18 s (breit) (3H); 7.37-7.42 m (3H); 7.51-

7.65 m (3H); 7.67 d (J = 10 Hz, 1H); 11.90 s (breit) (1H).

Example 90

6 - [[2- (3-methylphenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is prepared according to general prescription 9.

D.C. 92-94 ° C

Example 91

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

a) 6-methoxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole was obtained by converting 4-methoxy-N-phenyl-o-phenylenediamine with ethyl-4-methylbenzimidate hydrochloride (prepared by: DeWolfe und Augistine; J Organ Chem .; 30; 699) according to general prescription 4.

D.C. 150-152 ° C

b) 6-Hydroxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole is prepared by converting 6-methoxy-2- (4-methylphenyl) -1-phenyl-1H-benzimidazole according to general prescription 7 .

D.C. 257-264 ° C

6 - [[2- (4-Methylphenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-2- (4-methylphenyl) -1-phenyl - 1H-benzimidazole with 6-bromohexanoic acid methyl ester according to the general prescription 8.

D.C. 99-102 ° C

Example 92

6 - [[2- (4-Methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester is obtained by conversion of 6-hydroxy-2- (4-methylphenyl) -1- phenyl-1H-benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 107-109 ° C

Example 93

6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by converting 6 - [[2- (4-methylphenyl) -1- Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.33-1.49 ppm m (2H); 1.50-1.62 m (2H); 1.64-177 m (2H); 2.22 t (J = 7.5 Hz, 2H); 2.30 s (3H); 3.90 t (J =

7.5 Hz, 2H); 6.62 d (J = 2 Hz, 1H); 6.94 dd (J = 10.2 Hz, 1H); 7.15 d (J = 8 Hz, 2H); 7.36 d (J = 8 Hz, 2H); 7.40 dd (J = 8.1.5 Hz, 2H); 7.52-7.62 m (3H); 7.68 d (J = 10 Hz, 1H).

Example 94

6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexan-1-ol is obtained by converting the methyl ester to 6 - [[2- (4-methylphenyl) -1-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 11.

D.C. 150-152 ° C

Example 95

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

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

0.4 g of 4-methoxy-N ² -phenyl-o-phenylidenediamine are dissolved in 8 ml of N, N-dimethylformamide and the solution is mixed with 0.7 g of ethyl-2-ethoxy-1,2-dihydroquinoline-1-carboxylate and 0.34 g of isonicotinic acid. It is stirred for 16 hours at 100 ° C, after cooling it is mixed with water, extracted three times with ethyl acetate, the combined organic phases washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. After chromatographic purification on silica gel, the amide is absorbed in 5 ml of 6 N aqueous hydrochloric acid and heated for 3 hours counter-current. After cooling, stir in saturated sodium bicarbonate solution, extract the trick

65858 Bl with ethyl acetate, the combined extracts with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl ₃ ): δ = 3.80 ppm s (3H);

6.66 ppm d (J = 2 Hz, 1H); 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 = 10 Hz, 1H); 8.53 d (breit) (J = 6 Hz, 2H).

b) 6-hydroxy-1-phenyl-2- (4-pyridinyl) 1H-benzimidazole is obtained by converting 6-methoxy-1-phenyl-2- (4-pyridinyl) -1H-benzimidazole according to general operating instructions 7 .

1 H-NMR (CD ₃ OD): delta = 6.52 ppm d (J = 2 Hz, 1H); 6.82 dd (J = 10.2 Hz, 1H); 7.28-7.33 n (2H); 7.39 dd (J = 8, 1.5 Hz, 2H); 7.49-7.57 m (4H); 8.40 d (breit) (J = 6 Hz, 2H).

6 - [[1-Phenyl-2- (4-pyridinyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6-hydroxy-1-phenyl-2- (4-pyridinyl) - 1 H-benzimidazole according to general prescription 8.

D.C. 100-103 ° C

Example 96

6 - [[1-Phenyl-2- (4-pyridinyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[1-phenyl-2- (4-pyridine) methyl ester ) -1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 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-1 H -benzimidazole

c) 1,2-diphenyl-6-hydroxy-5,7-dinitro-1H-benzimidazole g 1,2-diphenyl-6-hydroxy-1H-benzimidazole was dissolved in 45 ml of acetic acid and at 10-15 ° C. a mixture of drops with a solution of 1.67 g of potassium nitrite in 15 ml of water. It was stirred in an ice bath for 2 h at 20 ° C, the reaction mixture was concentrated in vacuo and purified by chromatography on silica gel.

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

b) Ή-NMR (D ₆ -DMSO): δ = 7.05 ppm d (J = 10 Hz, 1H); 7.30-7.53 m (10H); 7.82 d (J = 10 Hz, 1H); 10.83 s (1H).

c) Ή-NMR (D ₆ -DMSO); delta = 7.32-7.58 ppm m (10H); 8.67 s (1H).

6 - [(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-5-nitro-1 H-benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 123 ° C

Example 98

6 - [(1,2-Diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-5-nitro-1H- benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 115-117 ° C

Example 99

6 - [(1,2-Diphenyl-7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-7-nitro-1H -benzimidazole with 6-bromohexanoic acid methyl ester according to general prescription 8.

D.C. 110-112 ° C

Example 100

6 - [(1,2-Diphenyl-7-nitro-1H-benzimide azol-6-yl) oxy] hexanoic acid isopropyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-5-nitro-1H- benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 88 ° C

Example 101

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

340 m 6 - [(1,2-diphenyl7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is hydrogenated with Raney nickel in methanol

65858 Bl at 50 ° C in autoclave and normal pressure. After the absorption of hydrogen is complete, the catalyst is removed by filtration and concentrated in vacuo.

bp 113-115 ° C

Example 102

6 [(7-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester was prepared analogously to the procedure described in Example 101 by converting isopropyl ester to 6 - [(1,2 -diphenyl-7-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid.

1 H-NMR (CDCl ₃ ): δ = 1.22 ppm d (J =

7.5 Hz, 6H); 1.43-1.88 m (6H); 2.301 (J = 7.5 Hz, 2H); 4,041 (J = 7.5 Hz, 2H); 5.00 sp (J = 7.5 Hz, 1H); 6.97 d (J = 7.5 Hz, 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 is obtained by conversion of 5,7-dinitro-1,2-diphenyl-6 -hydroxy-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to the general prescription 8.

D.C. 88-91 ° C

Example 104

6 - [(5,7-Dinitro-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is obtained by conversion of 5,7-dinitro-1,2-diphenyl-6-hydroxy -1H-benzimidazole with isopropyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 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-dinitrophenyl

0.41 g of 1,3-difluoro-4,6-dinitrobenzene were dissolved in 8 ml of 0.5 N aqueous sodium hydroxide solution and heated for 2 hours counter-current. After cooling, it is diluted with water and extracted three times with diethyl ether. The aqueous phase was acidified by addition of 1N hydrochloric acid and extracted with diethyl ether. The organic phase was dried over sodium sulfate and concentrated in vacuo.

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

b) 2,4-dinitro-5-hydroxydiphenylamine

To a suspension of 50 mg of 5-fluoro-2,4-dinitrophenyl in 0.5 ml of ethanol was added 100 µl of aniline, stirred for 30 min and allowed to stand for 15 h. It is sucked off with a suction filter, the solid is washed with 1N aqueous hydrochloric acid and dried in vacuo.

1 H-NMR (CDCl ₃ ): δ = 6.58 ppm s (1H); 7.31 d (J = 10 Hz, 2H); 7.39 dd (J = 10, 10 Hz, 1H); 7.51 dd (J = 10, 10 Hz, 2H); 9.20 s (1H); 9.90 s (breitX1H); 10.97 s (breit) (1H).

c) Acetic acid- (2,4-dinitro-5-phenylamino) phenyl ester

To 275 mg of 2,4-dinitro-5-hydroxydiphenylamine in 1 ml of pyridine was added 0.11 ml of acetic anhydride and stirred for 30 min in an ice bath, then stirred for another 1 h at 20 ° C. After dilution with ethyl acetate, it was washed three times with glacial 1N aqueous hydrochloric acid, once with saturated potassium bicarbonate solution and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo.

1 H-NMR (CDCl ₃ ): δ = 2.34 ppm s (3H); 6.80 s (1H); 7.32 d (J = 10 Hz, 2H); 7.40 dd (J = 10.10 Hz, 1H); 7.52 dd (J = 10.10 Hz, 2H); 9.21 s (1H); 9.95 s (breit) (1H).

d) Acetic acid- (1,2-diphenyl-6-hydroxy-1H-benzimidazol-5-yl) amide is obtained by conversion of acetic acid- (2,4-dinitro-5-phenylamino) phenyl ester according to the general prescription 1 and subsequent conversion with trimetho-benzobenzoate according to the general prescription of operation 3.

1 H-NMR (CDCl ₃ ): δ = 2.26 ppm s (3H);

6.88 s (1H); 7.22-7.36 m (5H); 7.42-7.53 m (5H); 7.61 s (1H); 8.43 s (breit) (1H).

6 - [[5- (acetylamino) methyl ester -

1,2-Diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of acetic acid ((1,2-diphenyl-6-hydroxy-1H-benzimidazol-5-yl) amide with methyl ester of 6-bromohexanoic acid according to general prescription 8.

D.C. 128-130 ° C

Example 106

6 - [(5-amino-1,2-di isopropyl ester)

65858 B1 phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid is prepared by conversion of 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester according to general prescription 1.

1 H-NMR (CDCl ₃ ): δ = 1.23 ppm d (J =

7.5 Hz, 6H); 1.47-1.90 m (6H); 2,321 (J = 7.5 Hz, 2H); 3,951 (J = 7.5 Hz, 2H); 5.02 sp (J = 7.5 Hz, 1H); 6.60 s (1H); 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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with 4-bromobenzenesulfonic acid chloride.

D.C. 173-175 ° C

Example 108

6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [(1,2-diphenyl-5-nitro) methyl ester -1H-benzimidazol-6-yl) oxy] hexanoic acid according to general prescription 1.

1 H-NMR (CDCl ₃ ): δ = 1.48-1.88 ppm (6H); 2.36 t (J = 7.5 Hz, 2H, CH = CO); 3.67 s (3H); 3.941 (J = 7.5 Hz, 2H); 6.60 s (1H); 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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is converted according to the general prescription for operation 13 with 4-chlorobenzenesulfonic acid chloride

D.C. Mp 157-159 ° C

Example 110

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general instructions for operation 13 with 4-chlorobenzenesulfonic acid chloride.

D.C. Mp 158-159 ° C

Example 111

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -

1,2-Diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] - methyl ester.

1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

D.C. 201-203 ° C

Example 112

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with 3-methylbenzenesulfonic acid chloride.

D.C. 149-151 ° C

Example 113

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with 4-methylenebenzenesulfonic acid chloride.

D.C. 139-141 ° C

Example 114

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with 4-methoxybenzylsulfonic acid chloride.

1 H-NMR (CDCl ₃ ): δ = 1.25 ppm d (J =

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

Example 115

6 - [[1,2-diphenyl-5 [[[[(4-trifluoromethyl) phenyl] sulfonyl] amino]] isopropyl ester]

65858 Bl

1H-Benzimidazol-6-yl] oxy] hexanoic acid 6 - [(5-amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription 13 with 4- (trifluoromethyl) benzenesulfonic acid chloride

D.C. 170-171 ° C

Example 116

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with 4- (acetylamino) benzenesulfonic acid chloride.

D.C. 100-102 ° C

Example 117

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with 3-chlorobenzylsulfonic acid chloride.

D.C. Mp 163-167 ° C

Example 118

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with propansulfonic acid chloride.

D.C. 126-128 ° C

Example 119

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

6 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester is converted according to the general prescription for operation 13 with benzene methanesulfonic acid chloride.

D.C. 137-138 ° C

Example 120

4- [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] benzoic acid methyl ester is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 4- (bromomethyl methyl ester). ) -benzoic acid according to the general prescription 8.

D.C. 180-184 ° C

Example 121

4 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] methylbenzoic acid is obtained by conversion of 4 - [(1,2-diphenyl-1H-benzimidazol-6yl) oxy] methylbenzoic acid methyl ester according to the general prescription 9.

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

7.89 d (J = 8 Hz, 2H).

Example 122

4 - [[1- (3-Methylphenyl) - methyl ester -

2-Phenyl-1H-benzimidazol-6-yl] oxy] benzoic acid is prepared by converting 6-hydroxy-1- (3-methylphenyl) -2-phenyl-1H-benzimidazole with 4- (bromomethyl) benzoyl methyl ester acid according to the general prescription 8.

D.C. 138-142 ° C

Example 123

4 - [[1- (4-Methylphenyl) - methyl ester -

2-Phenyl-1H-benzimidazol-6-yl] oxy] methylbenzoic acid is obtained by converting 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole with 4- (bromomethyl) methyl ester benzoic acid according to general prescription 8.

D.C. 145-148 ° C

Example 124

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

0.2 g of [(1,2-diphenyl-1H-benzimidazol-6yl) oxy] ethan-1-ol are suspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. 0.1 ml of bromoacetic acid tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfane and 1.45 ml of 32% sodium hydroxide were added and stirred for 48 h. New 0.1 ml of bromoacetic acid tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfate were added and the mixture was allowed to stand for 48 h.

65858 Bl Tres bath. Finally, it was diluted with water and extracted three times with toluene. The combined organic phases were washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 1.43 ppm s (9H); 3.911 (J = 6 Hz, 2H); 4.10 s (2H); 4.171 (J = 6 Hz, 2H); 6.75 d (J = 2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7.24-7.36 m (5H); 7.45-7.56 m (5H); 7.76 d (J = 10 Hz, 1H).

Example 125

2- (2 - ((1,2-diphenyl-1H-benzimidazol-6yl) oxy] ethoxy] acetic acid mg tert-butyl ester of 2- (2 - ((1,2-diphenyl-1H-benzimidazol-6- il) oxy] ethoxy] acetic acid was dissolved in 0.5 ml of trifluoroacetic acid and stirred in 0.5 ml of trifluoroacetic acid for 48 hours. It was then diluted with water and extracted three times with ethyl acetate. sodium chloride, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

D.C. 134-136 ° C

Example 126

2- (2 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] acetic acid methyl ester mg 2- (2 - ((1,2-diphenyl-1H-benzimidazol-6-yl) The oxy] ethoxy] acetic acid was dissolved in 0.4 ml of N, N-dimethylformamide and mixed with 29 mg of cesium carbonate and 50 µl of methyl iodide, stirred for 20 h, then concentrated in vacuo and chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 3.73 ppm s (3H); 3.931 (J = 6 Hz, 2H); 4.181 (J = 6 Hz, 2H); 4.25 s (2H); 6.73 d (J = 2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7.25-7.42 m (5H); 7.46-7.58 m (5H); 7.77 d (J = 10 Hz, 1H).

1 H-NMR (CDCl ₃ ): δ = 1.43 ppm s (9H); 3.911 (J = 6 Hz, 2H); 4.10 s (2H); 4.171 (J = 6 Hz, 2H); 6.75 d (J = 2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7.24-7.36 m (5H); 7.45-7.56 m (5H); 7.76 d (J = 10 Hz, 1H).

Example 125

2- (2 - ((1,2-diphenyl-1H-benzimidazol-6yl) oxy] ethoxy] acetic acid mg tert-butyl ester of 2- (2 - ((1,2-diphenyl-1H-benzimidazole-6 -yl) oxy] ethoxy] acetic acid was dissolved in 0.5 ml of trifluoroacetic acid and stirred in 0.5 ml of trifluoroacetic acid for 48 hours. It was then diluted with water and extracted three times with ethyl acetate. of sodium chloride, dried over sodium sulfate and concentrated in vacuo The residue was chromatographed on silica gel.

D.C. 134-136 ° C

Example 126

2- (2 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] acetic acid methyl ester mg 2- (2 - ((1,2-diphenyl-1H-benzimidazol-6-yl) The oxy] ethoxy] acetic acid was dissolved in 0.4 ml of N, N-dimethylformamide and mixed with 29 mg of cesium carbonate and 50 µl of methyl iodide, stirred for 20 h, then concentrated in vacuo and chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 3.73 ppm s (3H); 3.93 t (J = 6 Hz, 2H); 4.181 (J = 6 Hz, 2H); 4.25 s (2H); 6.73 d (J = 2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7.25-7.42 m (5H); 7.46-7.58 m (5H); 7.77 d (J = 10 Hz, 1H).

Example 127

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

0.2 g of [(1,2-diphenyl-1H-benzimidazol-6yl) oxy] ethan-1-ol are suspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. 60 µL of acrylic acid tert-butyl ester, 13 mg of tetrabutylammonium hydrogen sulfate and 1.45 ml of 32% sodium hydroxide were added and stirred for 48 h. An additional 60 microl of acrylic acid tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfate were added and left in an ultrasonic bath for 48 hours. Finally, it was diluted with water and extracted three times with toluene. The combined organic phases were washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 1.45 ppm s (9H); 2.52 t (J = 8 Hz, 2H); 3.73-3.84 m (4H); 4.10 t (J = 6 Hz, 2H); 6.72 d (J = 2 Hz, 1H); 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, 1H).

65858 Bl

Example 128

3- [2 - [(1,2-diphenyl-1H-benzimidazol-6yl) oxy] ethoxy] propanoic acid mg of 3- [2 - [(1,2-diphenyl-1H-benzimidazyl-6-yl) tert-butyl ester ) oxy] ethoxy] propanoic acid was dissolved in 0.5 ml of trifluoroacetic acid and stirred for 15 h. Finally, it was diluted with water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

1 H-NMR (D ₆ -DMSO): delta = 2.26 ppm t (J = 8 Hz, 2H); 3.60-3.70m (4H); 3.98-4.06 m (2H); 6.65 d (J = 2 Hz, 1H); 6.94 dd (J = 10.2 Hz, 1H); 7.30-7.62 m (10H); 7.68 d (J = 10 Hz, 1H).

Example 129

3- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] propanoic acid methyl ester mg 3- [2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] propanoic acid was dissolved in 0.4 ml of N, N-dimethylformamide, mixed with 28 mg of cesium carbonate and 50 µl of methyl iodide and stirred for 30 h. Finally, it was diluted with water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

D.C. 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-6yl) oxy] propan-1-ol were suspended in 1.7 ml of toluene and 0.7 ml of tetrahydrofuran. Add 60 [mu] l of acrylic acid tert-butyl ester, 13 mg of tetrabutylammonium hydrogen sulfate and 1.47 ml of 32% sodium hydroxide and stir for 48 h. 60 µl of acrylic acid tert-butyl ester and 13 mg of tetrabutylammonium hydrogen sulfate were added and the mixture was allowed to stand in an ultrasonic bath for 48 h. Finally, it was diluted with water and extracted three times with toluene. The combined organic phases were washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

D.C. 95-98 ° C

Example 131 ((E / 7) -5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pent-4-ene methyl ester

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

5.1 g of 5-methyl-2-nitrodiphenylamine in 55 ml of ethanol are hydrogenated according to general prescription 1. The crude product is mixed with trimethylorthobenzoate according to general prescription 3.

D.C. 134-136 ° C

b) 1,2-diphenyl-1H-benzimidazol-6-yl carbaldehyde g 1,2-diphenyl-6-methyl-1H-benzimidazole are suspended in 31 ml of 40% sulfuric acid and mixed with 13.5 g of ceramonium nitrate . It was stirred for 2.5 h at 80 ° C, cooled to 20 ° C and stirred very carefully in saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate; The combined extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 7.30-7.42 ppm m (5H); 7.50-7.66 m (5H); 7.81 d (J = 2 Hz, 1H);

7.89 dd (J = 8.2 Hz, 1H); 8.00 d (J = 8 Hz, 1H); 10.05 s (1H).

(E / Z) -1- (1,2-Diphenyl-1H-benzimidazol-6-yl) pent-4-enoic acid methyl ester is obtained by converting 1,2-diphenyl-1H-benzimidazole-6-carbaldehyde according to the general prescription for working 12 with 3-carboxypropyltriphenylphosphonium bromide.

1 H-NMR (CDCl ₃ ): δ = 2.40-2.71 ppm m (4H); 3.68 (3.66) is s (3H); 5.56-5.64 (6.126.22) is m (1H); 6.50 d (J = 18 Hz, 1H); 6.58 d (breit) (J = 12 Hz, 1H); 7.12 (7.15) is s (breit) (1H); 7.25-7.40m (6H); 7.45-7.62 m (5H); 7.80 (7.83) is d (J = 8 Hz, 1H).

Example 132

E-5- (1,2-diphenyl-1H-benzimidazol-6yl) pent-4-enoic acid is obtained by converting (E / g) -5- (1,2-diphenyl-1H-benzimidazole) methyl ester -6-yl) pent-4-enoic acid according to general prescription 9.

65858 Bl

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

Example 133

5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pentanoic acid methyl ester is obtained by converting (E / 2) -5- (1,2-diphenyl-1H-benzimidazol6-yl) methyl ester ) pent-4-enoic acid according to general prescription 1.

1 H-NMR (CDCl ₃ ): δ = 1.63-1.72 ppm m (4H); 2.30-2.39 m (2H); 2.68-2.77 m (2H); 3.65 s (3H); 7.04 s (breit) (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 = 8 Hz, 1H).

Example 134

5- (1,2-Diphenyl-1H-benzimidazol-6-yl) pentanoic acid is obtained by conversion of 5- (1,2-diphenyl-1H-benzimidazol-6-yl) pentanoic acid methyl ester according to the general requirement for work 9,

D.C. Mp 192-193 ° C

Example 135

(E / 2) -6- (1,2-Diphenyl-1H-benzimidazol-6-yl) hex-5-enoic acid methyl ester is obtained by converting 1,2-diphenyl-1H-benzimidazole-6-carbaldehyde according to the general prescription for work 12 with 4-carboxybutyltriphenylphosphonium bromide.

1 H-NMR (CDCl ₃ ): δ = 1.72-1.88 ppm m (2H); 2.20-2.42 m (4H); 3.65 (3.67) is s (3H, CH 2); 5.57-5.68 (6.10-6.20) is m (1H); 6.48 d (J = 18 Hz, 1H); 6.56 d (breit) (J = 12 Hz, 1H); 7.12 (7.16) is s (breit) (1H); 7.25-7.38 m (6H); 7,457.60 m (5H); 7.80 (7.84) is d (J = 8 Hz, 1H).

Example 136 (E / 7) -6- (1,2-diphenyl-1H-benzimidazol-6yl) hex-5-enoic acid was obtained by converting (E / Z) -6- (1,2-) methyl ester diphenyl-1H-benzimidazole-

6-yl) hex-5-enoic acid according to general prescription 9.

1 H-NMR (CDCl ₃ ): δ = 1.74-1.89 ppm m (2H); 2.22-2.43 m (4H); 5.58-5.68 (6.10-6.22) is m (1H); 6.47 d (J = 18 Hz, 1H); 6.55 d (breit) (J = 12 Hz, 1H); 7.11 (7.14) is s (breit) (1H); 7,257.40 m (6H); 7.48-7.59 m (5H); 7.80 (7.85) is d (J = 8 Hz, 1H).

Example 137

6- (1,2-Diphenyl-6-yl) hexanoic acid methyl ester is prepared by converting (1,2-diphenyl-1H-benzimidazol-6-yl) hex-5-enoic acid methyl ester to work 1.

1 H-NMR (CDCl ₃ ): δ = 1.32-1.43 ppm m (2H); 1.62-1.74 m (4H); 2.311 (J = 7.5 Hz, 2H); 2.72 t (J = 7.5 Hz, 2H); 3.56 s (3H); 7.02 s (breit) (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 = 8 Hz, 1H).

Example 138

6- (1,2-Diphenyl-1H-benzimidazol-6-yl) hexanoic acid is obtained by converting 6- (1,2-diphenyl-1H-benzimidazol-6-yl) hexanoic acid methyl ester according to the general requirement to work 9.

1 H-NMR (CDCl ₃ ): δ = 1.30-1.45 ppm m (2H); 1.54-1.74 m (4H); 2,321 (J = 7.5 Hz, 2H); 2.701 (J = 7.5 Hz, 2H); 7.02 s (breit) (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 = 8 Hz, 1H).

Example 139

(E / 2) -7- (1,2-Diphenyl-1H-benzimidazol-6-yl) hept-6-enoic acid methyl ester is obtained by converting 1,2-diphenyl-1H-benzimidazole-6-carbaldehyde according to the general prescription for work 12 with 5-carboxypentyltriphenylphosphonium bromide.

1 H-NMR (CDCl ₃ ): δ = 1.43-1.55 ppm m (2H); 1.58-1.72 m (2H); 2.18-2.38 m (4H); 3.65 (3.66) is s (3H, CH ₃ ); 5.58-5.68 (6.12-6.22) is m (1H); 6.45 d (J = 18 Hz, 1H); 6.54 d (breit) (J = 12 Hz, 1H); 7.12 (7.14) is s (breit) (1H); 7.26-7.40 m (6H); 7.48-7.60 m (5H); 7.80 (7.83) is d (J = 8 Hz, 1H).

Example 140 (E / Z) -7- (1,2-diphenyl-1H-benzimidazol-6yl) hept-6-enoic acid was obtained by conversion of (E / Z) -7- (1,2) methyl ester -diphenyl-1H-benzimidazol-6-yl) hept-6-enoic acid according to general prescription 9.

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

65858 Bl

Example 141

7- (1,2-Diphenyl-1H-benzimidazol-6-yl) heptanoic acid methyl ester is obtained by converting (E / Z) -7- (1,2-diphenyl-1H-benzimidazole-6- or il) hept-6-enoic acid according to general prescription.

1 H-NMR (CDCl 3): δ = 1.30-1.42 ppm 1 (4H); 1.55-1.70 m (4H); 2.30 t (J = 7.5 Hz, 2H);

2.68 t (J = 7.5 Hz, 2H); 3.56 s (3H); 7.02 s (breitXIH); 7.18 dd (J = 8.2 Hz, 1H); 7.28-7.35 m (5H); 7.45-7.58 m (5H); 7.79 d (J = 8 Hz, 1H).

Example 142

7- (1,2-diphenyl-1H-benzimide azol-6-yl) heptanoic acid is obtained by conversion of 7- (1,2-diphenyl-1H-benzimidazol-6-yl) heptanoic acid methyl ester

D.C. 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 2,4-diaminodiphenylamine was converted according to the general prescription for work 3 with trimethylorthobenzoate.

1 H-NMR (CDCl ₃ ): delta = 6.70 ppm dd (J =

7.5.2 Hz, 1H); 7.06 d (J = 7.5 Hz, 1H); 7.18 d (J = 2 Hz, 1H); 7.28-7.60 m (10 H).

5-Amino-1,2-diphenyl-1H-benzimidazole was converted according to the general prescription for operation 13 with benzenesulfonic acid chloride.

143: bp Mp 196-205 ° C

144: 1 H-NMR (CDCl ₃ ): δ = 6.94 ppm dd (J = 7.5, 2 Hz, 1H); 7.20 d (J = 2 Hz, 1H); 7,268.04 m (21H).

Example 145

3-chloro-L1- (1,2-diphenyl-1H-benzimidazol5-yl) benzenesulfonamide

Example 146

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

5-Amino-1,2-diphenyl-1H-benzimidazole is converted according to the general prescription for operation 13 with 3-chlorobenzenesulfonic acid chloride.

145: bp 160-162 ° C

146: 1 H-NMR (CDCl ₃ ): δ = 6.93 ppm dd (J = 7.5, 2 Hz, 1H); 7.25 d (J = 2 Hz, 1H);

7.28-7.57 m (13H); 7.66 d (breit) (2H); 7.90 d (breit) (2H); 8.00 d (breit) (2H).

Example 147

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

5- Amino-1,2-diphenyl-1H-benzimidazole was converted according to the general prescription for operation 13 with 4-chlorobenzenesulfonic acid chloride.

1 H-NMR (CDCl ₃ ): δ = 6.86 ppm s (breit) (1H); 7.11 d (J = 7.5.2 Hz, 1H); 7.17 d (J = 2 Hz, 1H); 7.25-7.55 m (12H); 7.70 d (J = 10 Hz, 2H).

Example 148

4- 6poM-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

D.C. Mp 135-239 ° C

149 N- (4-bromophenylsulfonyl) -N- (1,2-diphenyl-1H-benzimidazol-5-yl) -4-bromobenzenesulfonamide

5- Amino-1,2-diphenyl-1H-benzimidazole is converted according to the general prescription for operation 13 with 4-bromobenzenesulfonic acid chloride.

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

7.28- 7.43 m (11H); 7.72 d (J = 10 Hz, 2H); 7.86 d (J = 10 Hz, 2H).

Example 150

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

Example 151

N, 1,2-diphenyl-1H-benzimidazole-L1 - [(3-trifluoromethyl) phenylsulfonyl] - (3-trifluoromethyl) benzenesulfonamide

5- Amino-1,2-diphenyl-1H-benzimidazole is converted according to the general prescription for operation 13 with (3-trifluoromethyl) benzenesulfonic acid chloride

150: bp 116-121 ° C

151: bp 238-241 ° C

Example 152

3-methyl-L- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide

Example 153

N- (1,2-diphenyl-1H-benzimidazol-5-yl) N- (3-methylphenylsulfonyl) -3-methylbenzenesul

65858 Bl phonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is converted according to the general prescription for operation 13 with 3-methylbenzenesulfonic acid chloride.

152: bp Mp 192-195 ° C

153: bp 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 converted according to the general prescription for operation 13 with 4-methylbenzenesulfonic acid chloride.

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

155: bp 234-236 ° C

Example 156

4- MeTOKCH-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 converted according to the general operating instructions 13 with 4-methoxybenzenesulfonic acid chloride.

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

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

Example 158

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

Example 159

N- (1,2-diphenyl-1H-benzimidazol-5-yl) N (propylsulfonyl) -propanesulfonamide

5-Amino-1,2-diphenyl-1H-benzimidazole is converted according to the general prescription for operation 13 with propanbenzenesulfonic acid chloride.

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

159: 1 H-NMR (CDCl ₃ ): δ = 1.08 ppm t (J = 7.5 Hz, 3H); 1,121 (J = 7.5 Hz, 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) benzolmethanesulfonamide

5- Amino-1,2-diphenyl-1H-benzimidazole is converted according to the general prescription for operation 13 with benzene methanesulfonic acid chloride.

D.C. 185-188 ° C

Example 161

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

Example 162

6- [1- (1,2-Diphenyl-1H-benzimidazol-5-yl) -B1 - [(5-methoxycarbonyl) phenyl] amino] hexanoic acid methyl ester

To a solution of 285 mg of 5-amino-1,2-diphenyl-1H-benzimidazole in 5 ml of methanol was added 207 mg of 6-bromohexanoic acid methyl ester, 138 mg of potassium carbonate and 150 mg of sodium iodide and stirred for 3 h at 20 ° C. It was combined with water, extracted three times with ethyl acetate, the combined organic phases were dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

161: bp 109-113 ° C

162: 1 H-NMR (CDCl 3): δ = 1.30-1.43 m (4H); 1.53-1.73 m (8H); 2.321 (J = 7.5 Hz, 4H); 3.301 (J = 7.5 Hz, 4H); 3.68 s (6H); 6.75 dd (J =

10.2 Hz, 1H); 7.10 d (J = 10 Hz, 1H); 7.14 d (J = 2 Hz, 1H); 7.23-7.35 m (5H); 7.42-7.58 m (5H).

Example 163

6- [[1,2-diphenyl-1H-benzimidazol-5yl] amino] hexanoic acid is obtained by converting 6 - [[1,2-diphenyl-1H-benzimidazol-5yl] amino] hexanoic acid methyl ester prescription for work 9.

1 H-NMR (D ₆ -DMSO): delta = 1.35-1.50 ppm m (2H); 1.50-1.68 m (4H); 2.231 (J = 7.5 Hz, 2H); 3,051 (J = 7.5 Hz, 2H); 6.67 dd (J = 10.2 Hz,

65858 Bl

1H); 6.80 d (J = 2 Hz, 1H); 6.92 d (J = 10 Hz, 1H); 7.30-7.40m (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 g 3-fluoro-4-nitrophenyl and 3.8 g 4-benzyloxyaniline were stirred for 6.5 h at 150 ° C. . The mixture was then diluted with dichloromethane. After extraction twice with 1 N aqueous hydrochloric acid and washing with water, extract twice with 2N aqueous sodium hydroxide. The basic aqueous phase was mixed with ethyl acetate and 1N aqueous hydrochloric acid. After phase separation, the organic phase was repeatedly extracted with 1N hydrochloric acid. After washing the organic phase with saturated sodium chloride solution, it was dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

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

b) 6 - [[4-Nitro-3 - [[4- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid methyl ester is obtained by converting (5-hydroxy-2-nitrophenyl) [4- ( phenylmethoxy) phenyl] amine with 6-bromohexanoic acid methyl ester according to general prescription 9.

1 H-NMR (CDCl ₃ ): δ = 1.37-1.50 m (2H); 1.59-1.80 m (4H); 2.33 t (J = 7.5 Hz, 2H);

3.67 s (3H); 3.83 t (J = 7.5 Hz, 2H); 5.12 s (2H); 6.24-6.33 m (2H); 7.04 d (J = 8 Hz, 2H); 7.21 d (J = 8 Hz, 2H); 7.32-7.50 m (5H); 8.17 d (J = 8 Hz, 1H); 9.66 s (1H).

6 - [[2-Phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by reducing the 6 - [[4- nitro-3 - [[4- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid according to general prescription 2 and final cyclization with trimethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl ₃ ): δ = 1.43-1.58 m (2H); 1.65-1.86 m (4H); 2.351 (J = 7.5 Hz, 2H); 3.67 s (3H); 3.941 (J = 7.5 Hz, 2H); 5.14 s (2H); 6.64 d (J = 2 Hz, 1H); 6.95 dd (J = 8.2 Hz, 1H); 7.11 d (J = 8 Hz, 2H); 7.18-7.61 m (12H); 7.74 d (J = 8 Hz, 1H).

Example 165

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

6 - [[2-Phenyl-1- [4- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is converted according to general working order 9.

1 H-NMR (D ₆ -DMSO): delta = 1.36-1.62 m (4H); 1.65-1.78 m (2H); 2.22 t (J = 7.5 Hz, 2H); 3.921 (J = 7.5 Hz, 2H); 5.18 s (2H); 6.59 d (J = 2 Hz, 1H); 6.92 dd (J = 8.2 Hz, 1H); 7.20 d (J = 8 Hz, 2H); 7.30-7.54 m (12H); 7.66 d (J = 8 Hz, 1H).

Example 166

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

6 - [[2-Phenyl-1- [4- (phenylmethoxy) phenyl] 1H-benzimidazol-6-yl] oxy] hexanoic acid is converted according to general prescription 1.

1 H-NMR (D ₆ -DMSO): delta = 1.37-1.79 m (6H); 2.22 t (J = 7.5 Hz, 2H); 3.92 t (J = 7.5 Hz, 2H); 6.60 d (J = 2 Hz, 1H); 6.91 dd (J = 8, 2 Hz, 1H); 6.94 d (J = 8 Hz, 2H); 7.20 d (J = 8 Hz, 2H); 7.36 m (3H); 7.52 m (2H); 7.63 d (J = 8 Hz, 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 g 3-fluoro-4-nitrophenyl and 3.81 g of 3-benzyloxyaniline were stirred for 22 h at 150 ° C. Finally, it was absorbed in a small amount of dichloromethane and chromatographed directly on silica gel.

1 H-NMR (CDCl ₃ ): δ = 5.10 ppm s (2H); 5.82 s (br) (1H); 6.27 dd (J = 8.2 Hz, 1H); 6.48 d (J = 2 Hz, 1H); 6.86 m (3H); 7.28-7.48 m (5H); 8.15 d (J = 8 Hz, 1H); 9.52 s (br) (1H); 10.71 s (1H).

b) 6 - [[4-Nitro-3 - [[3 (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid methyl ester is obtained by conversion of (5-hyd

65858bloxy-2-nitrophenyl) [3- (phenylmethoxy) phenyl] amine with 6-bromohexanoic acid methyl ester according to general working order 8.

1 H-NMR (CDCl ₃ ): δ = 1.40-1.53 w (2H); 1.61-1.82 m (4H); 2,341 (J = 7.5 Hz, 2H);

3.67 s (3H); 3.88 t (J = 7.5 Hz, 2H); 5.10 s (2H); 6.33 dd (J = 8.2 Hz, 1H); 6.58 d (J = 2 Hz, 1H); 6.83-6.96 m (3H); 7.28-7.49 m (5H); 8.17 d (J = 8 Hz, 1H); 9.74 s (br).

6 - [[2-Phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by reducing 6 - [[4-nitro-3- [ [3- (phenylmethoxy) phenyl] amino] phenyl] oxy] hexanoic acid according to general prescription 2 and final cyclization with trimethylorthobenzoate according to general prescription 3.

1 H-NMR (CDCl ₃ ): δ = 1.45-1.60 w (2H); 1.66-1.88 m (4H); 2.351 (J = 7.5 Hz, 2H);

3.68 s (3H); 3.931 (J = 7.5 Hz, 2H); 5.02 s (2H);

6.69 d (J = 2 Hz, 1H); 6.90 m (2H); 6.97 dd (J = 8.2 Hz, 1H); 7.11 ddd (J = 8.2.2 Hz, 1H); 7.28-7.46 m (9H); 7.78 d (J = 8 Hz, 1H).

Example 168

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

6 - [[2-Phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is converted according to general prescription 9.

1 H-NMR (CDCl ₃ ): δ = 1.49-1.62 m (2H); 1.67-1.88 m (4H); 2.391 (J = 7.5 Hz, 2H); 3.931 (J = 7.5 Hz, 2H); 5.03 s (2H); 6.68 d (J = 2 Hz, 1H); 6.91 m (3H); 6.98 dd (J = 8.2 Hz, 1H); 7.12 ddd (J = 8, 2.2 Hz, 1H); 7.29-7.47 m (8H); 7.57 d (J = 8 Hz, 2H); 7.81 d (J = 8 Hz, 1H).

Example 169

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

6 - [[2-Phenyl-1- [3- (phenylmethoxy) phenyl] 1H-benzimidazol-6-yl] oxy] hexanoic acid is converted according to general prescription 1.

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

Example 170

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

6 - [[2-Phenyl-1- [3- (phenylmethoxy) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is converted according to general working order 1.

1 H-NMR (D ₆ -DMSO): delta = 1.38-1.80 m (6H); 2.321 (J = 7.5 Hz, 2H); 3.59 s (3H); 3.941 (J = 7.5 Hz, 2H); 6.66 d (J = 2 Hz, 1H); 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 (2H); 7.67 d (J = 8 Hz, 1H).

Example 171

6 - [[1- (3-Nitrophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid ethyl ester is obtained by conversion of 6-hydroxy-1- (3-nitrophenyl) -2-phenylbenzimidazole (DE 4330959) with 6-bromohexanoic acid ethyl ester according to general prescription 8.

D.C. 104-106 ° C

Example 172

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

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

36.6 g of 4-amino-3-bromo-5-nitroanisole (J. Chem. Soc. 1966,1769) were placed in 750 ml of ethanol and mixed with 19.8 g of iron powder and 126 ml of acetic acid. After stirring for 2.5 h at 55 ° C, it was mixed with 350 ml of dichloromethane and basified with 2 N sodium hydroxide solution. After filtration through celite, it was washed with water and saturated sodium chloride solution and concentrated. The crude phenylindiamine thus obtained is converted according to the general prescription for work 3 with trimethylorthobenzoate.

D.C. 203-205 ° C

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

2.5 g of 4-bromo-6-methoxy-2-phenyl-1H-benzimidazole and 2.24 g of 4- (methylbenzene) boronic acid are stirred with 1.5 g of anhydrous copper (II) acetate and about 3 g of Molsieb in pyridine in

65858 B1 for 7 h at 100 ° C. After the addition of dichloromethane and celite, it was concentrated and chromatographed on silica gel with one hexane / ethyl acetate mixture.

D.C. 209-210 ° C

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

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%) were boiled for 5, 5 h. Finally, it is precipitated with water and the precipitate is sucked off. The latter was partitioned between ethyl acetate and 2 N sodium hydroxide. After washing the organic phases with water, it is concentrated.

D.C. 136-137 ° C

6 - [[4-Bromo-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 4-bromo-6-hydroxy-1 - ( 4-methylphenyl) 2-phenyl-1H-benzimidazole with 6-bromohexanoic acid methyl ester according to the general prescription 8.

D.C. 136 ° C

Example 173

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

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

D.C. 114-115 ° C

Example 174

6 - [[1- (4-Methylphenyl) -2phenyl-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 1953, 42) and 20.4 g of 4- (methylbenzene) boronic acid are converted according to the general requirement to work 14.

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

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

B) 5-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole is prepared from 5-methoxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazole according to general prescription 6.

D.C. 270 ° C

6 - [[1- (4-Methylphenyl) 2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester is obtained from 5-hydroxy-1- (4methylphenyl) -2-phenyl-1H- benzimidazole by conversion with 6-bromohexanoic acid methyl ester according to general prescription 8.

1 H-NMR (CDCl 3: δ = 1.48-1.92 m (6H); 2.381 (J = 7.5 Hz, 2H); 2.46 s (3H); 3.69 s (3H); 4.061 (J = 7.5 Hz, 2H); 6.89 dd (J = 8.2 Hz, 1H); 7.11 d (J = 8 Hz, 1H); 7.18 d (J = 8 Hz, 2H); 7.24-7.37 m (6H); 7.57 m (2H).

Example 175

6 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid is obtained from 6 - [[1- (4methylphenyl) -2-phenyl-1 methyl ester] N-benzimidazol-5-yl] oxy] hexanoic acid according to general prescription 9.

1 H-NMR (D ₆ -DMSO): delta = 1.41 -1.67 m (4H); 1.70-1.83 m (2H); 2.261 (J = 7.5 Hz, 2H); 2.43 s (3H); 4,051 (J = 7.5 Hz, 2H); 6.90 dd (J = 8, 2 Hz, 1H); 7.04 d (J = 8 Hz, 1H); 7.23-7.40m (8H); 7.52 m (2H); 11.92 s (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

4.84 g of 2-phenyl-5-hydroxy-1H-benzimidazole (Acad. Nauk. SSSR Ser. Chim. 8 1990, 1888) was prepared by conversion with 6-bromohexanoic acid methyl ester according to general operating instructions 8 .

1 H-NMR (CDCl 3: δ = 1.43-1.58 m (2H); 1.64-1.87 m (4H); 2.37 t (J = 7.5 Hz, 2H);

65858 Bl

3.69 s (3H); 3.941 (J = 7.5 Hz, 2H); 6.87 dd (J = 8.2 Hz, 1H); 7.02 s (no.); 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 is obtained by conversion of 6 - [[2-phenyl] methyl ester - 1H-benzimidazol-5-yl] oxy] hexanoic acid with 4- (thiomethylbenzene) boronic acid according to the operating instructions 14.

1 H-NMR (CDCl 3): δ = 1.48-1.61 w (2H); 1.66-1.92 m (4H); 2.36 t (J = 7.5 Hz, 2H); 2.54 s (3H); 3.68 s (3H); 4.05 t (J = 7.5 Hz, 2H); 6.90 dd (J = 8, 2 Hz, 1H); 7.11 d (J = 8 Hz, 1H); 7.22 d (J = 8 Hz, 2H); 7.27-7.49 m (6H); 7.57 m (2H).

Example 177

6 - [[2-Phenyl-1 - [(4-thiomethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[2-phenyl] methyl ester -1H-benzimidazol-5-yl] oxy] -hexanoic acid with 4- (thiomethylbenzene) boronic acid according to general prescription 14.

1 H-NMR (CDCl ₃ ): δ = 1.45-1.57 w (2H); 1.62-1.86 m (4H); 2.44 t (J = 7.5 Hz, 2H); 2.56 s (3H); 3.66 s (3H); 3.93 t (J = 7.5 Hz, 2H); 6.66 d (J = 2 Hz, 1H); 6.96 dd (J = 8, 2 Hz, 1H); 7.18-7.39 m (7H); 7.54 m (2H); 7.73 d (J = 8 Hz, 1H).

Example 178

6 - [[2-Phenyl-1- (3-thienyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester is obtained by converting 6 - [[2-phenyl] -1H methyl ester -benzimidazol-5-yl] oxy] hexanoic acid with thiophene-3-boronic acid according to general prescription 14.

1 H-NMR (CDCl ₃ ): δ = 1.48-1.62 m (2H); 1.66-1.92 m (4H); 2.47 t (J = 7.5 Hz, 2H);

3.68 s (3H); 4.041 (J = 7.5 Hz, 2H); 6.93 dd (J = 8.2 Hz, 1H); 6.98 dd (J = 5, 1 Hz, 1H); 7.18 d (J = 8 Hz, 1H); 7.28 dd (J = 3.1 Hz, 1H); 7.30-7.40m (4H); 7.46 dd (J = 5, 3 Hz, 1H); 7.60 m (2H).

Example 179

6 - [[2-Phenyl-1- (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 6 - [[2-phenyl] -1H-benzimidazole- 5-yl] oxy] hexanoic acid with thiophene-3-boronic acid according to general prescription 14.

1 H-NMR (CDCl 3): δ = 1.45-1.58 m (2H); 1.64-1.87 m (4H); 2.35 t (J = 7.5 Hz, 2H); 3.67 s (3H); 3.971 (J = 7.5 Hz, 2H); 6.74 d (J = 2 Hz, 1H); 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 (2H); 7.73 d (J = 8 Hz, 1H).

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 is obtained from 6-hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazole and 3-methoxybenzeneboronic acid according to the general prescription 14.

D.C. 120-122 ° C

b) 3 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol is obtained by converting 6- (3methoxyphenoxy) -1- (4-methylphenyl) -2- phenyl 1 H -benzimidazole according to general prescription for work 6 with the addition of 10 mol% hexane decyltributylphosphonium bromide.

D.C. Mp 252-253 ° C

4- [3 - [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] butanoic acid methyl ester is obtained by conversion of 3 - [[1- (4methylphenyl) 2-Phenyl-1H-benzimidazol-6-yl] oxy] phenol with 4-bromobutyric acid methyl ester.

1 H-NMR (CDCl ₃ ): δ = 2.00-2.13 m (2H); 2.43 s (3H); 2.501 (J = 7.5 Hz, 2H); 3.67 s (3H); 3.93 t (J = 7.5 Hz, 2H); 6.44-6.62 m (3H); 6.95 d (J = 2 Hz, 1H); 7.06 dd (J = 8.2 Hz, 1H); 7.12-7.22 m (3H); 7.25-7.39 m (5H); 7.59 m (2H); 7.87 d (J = 8 Hz, 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-methyl

65858 B1 phenyl) -2-phenyl-1H-benzimidazole is prepared from 6-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazole and 4-methoxybenzeneboronic acid according to general prescription 14.

1 H-NMR (CDCl 3): δ = 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 = 8 Hz, 2H); 7.25-7.41 m (5H); 7.57 m (2H); 7.82 d (J = 8 Hz, 1H).

b) 4- [[1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] phenol is obtained by converting 6- (3-methoxyphenoxy) -1- (4-methyl phenyl) ) -2-phenyl-1H-benzimidazole according to the general prescription for work 6 and the addition of 10 mol% hexadecyl tributylphosphonium bromide.

Ή-NMR (D ₆ -DMSO): δ = 2.38 s (3H); 6.61 d (J = 2 Hz, 1H); 6.74 d (J = 8 Hz, 2H); 6.86 d (J = 8 Hz, 2H); 6.91-7.01 m (2H); 7.22-7.41 m (6H); 7.49 m (2H); 7.75 d (J = 8 Hz, 1H); 9.32 s (1H).

4- [4 - [[1- (4-methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] butanoic acid methyl ester is obtained by conversion of 4 - ((1- (4-methylphenyl) -2 -phenyl-1H-benzimidazol-6-yl] oxy] phenol with 4-bromobutyric acid methyl ester according to general prescription 8.

1 H-NMR (CDCl ₃ ): δ = 2.03-2.16 m (2H);

2.42 s (3H); 2.53 t (J = 7.5 Hz, 2H); 3.69 s (3H); 3,971 (J = 7.5 Hz, 2H); 6.78-6.94 m (5H); 6.99 dd (J = 8.2 Hz, 1H); 7.16 d (J = 8 Hz, 2H); 7.24-7.38 m (5H); 7.57 m (2H); 7.79 d (J = 8 Hz, 1H).

Example 182

(4 - [(1- (4-methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] phenoxy] acetic acid methyl ester is obtained by conversion of 4 - ((1- (4-methylphenyl) -2- phenyl-1H-benzimidazol-6-yl] oxy] phenol with bromoacetic acid methyl ester according to the general prescription 8.

1 H-NMR 1 CDCl 3: δ = 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 = 8, Hz, 2H); 7.23-7.38 m (5H); 7.56 m (2H); 7.80 d (J = 8 Hz, 1H).

Example 183

4 - ((1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] butanoic acid methyl ester is obtained by converting 1,2-di-phenyl-6-hydroxy-1H-benzimidazole with bromobutanoic acid methyl ester according to the general prescription 8.

D.C. 107-110 ° C

Example 184

6 - [[2-Phenyl-1- (3-pyridino) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[2-phenyl-1H- methyl ester] benzimidazol-5-yl] oxy] hexanoic acid with pyridine-3-boronic acid according to general prescription 14.

MS (EI): 415 (molecular peak)

Example 185

6 - [[2-Phenyl-1- (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 6 - [(2-pyridyl] -1H- methyl ester). benzimidazol-5-yl] hexanoic acid with pyridine-3-boronic acid according to general prescription 14.

MS (EI): 415 (molecular peak)

Example 186

6 - ([2-Phenyl-1- (2-pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2-phenyl] -1H-benzimidazole- 5yl] oxy] hexanoic acid with 2-fluoro-pyridine according to general prescription 15.

MS (EI): 401 (molecular peak)

Example 187

6 - [[2-Phenyl-1- (2-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2-phenyl] -1H-benzimidazole- 5yl] oxy] hexanoic acid with 2-fluoro-pyridine according to general prescription 15.

MS (EI): 401 (molecular peak)

Example 188

6 - [(2-phenyl-1- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by converting 6 - [(2-phenyl] -1H-benzimidazole- 5yl] hexanoic acid with pyridine-4-boronic acid according to general prescription 14.

MS (EI): 415 (molecular peak)

65858 Bl

Example 189

6 - [[2- (4-Fluorophenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3- ( phenylamino) phenyl] oxy] hexanoic acid with 4-fluorobenzoyl chloride according to general prescription 5.

MS (EI): 432 (molecular peak)

Example 190

6 - [[2- (4-Methoxyphenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3- (phenylamino) methyl ester ) phenyl] oxy] hexanoic acid with 4-methoxybenzoyl chloride according to general prescription 5.

MS (EI): 444 (molecular peak)

Example 191

6 - [[2- (3-Fluorophenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3- ( phenylamino) phenyl] oxy] hexanoic acid with 3-fluorobenzoyl chloride according to general prescription 5.

MS (EI): 432 (molecular peak)

Example 192

6 - [[2- (4-Bromophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3- (phenylamino) methyl ester Phenyl] oxy] hexanoic acid with 4-bromobenzoyl chloride according to general prescription 5.

MS (EI): 492/494 (molecular peak) Example 193

6 - [[2- [4- (Trifluoromethyl) phenyl] -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino methyl ester] -3- (Phenylamino) phenyl] oxy] hexanoic acid with 4- (trifluoromethyl) benzoyl chloride according to general prescription started working 5.

MS (EI): 482 (molecular peak)

Example 194

6 - [[2- (4-fluorophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is obtained by conversion of 6 - [[2- (4-fluorophenyl) -1 methyl ester -phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid according to general prescription 9.

MS (EI): 418 (molecular peak)

Example 195

Nab - [[1-Phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3- methyl ester] (phenylamino) phenyl] oxy] hexanoic acid with benzothiophene-2-carboxylic acid chloride according to general prescription 5.

D.C. 129-130 ° C

Example 196

6 - [[1-Phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid was prepared according to general prescription 9.

D.C. 340 ° C (decomposition)

Example 197

6 - [[5-Hydroxy-1 (4-methylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid isopropyl ester

Example 198

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

4,5-dimethoxy-1,2-dinitrobenzene is hydrogenated to the diamino compound according to general prescription for job 1 and the diamino compound as a crude product according to general prescription for work 3 is cyclized with trimethylorthobenzoate to 5,6-dimethoxy-2-phenyl- 1H-benzimidazole (mp 131-133 ° C). This benzimidazole derivative was converted according to the general prescription for the operation of 14 with 4-methylphenylboronic acid to 5,6-dimethoxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazole- (mp 145-148 ° C). After cleavage of the ether with hydrobromic acid according to the general prescription for operation 6 to 5,6-dihydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazole (NMR of the hydrobromide (D ₆ -DMSO): delta = 2.42 ppm s (3H); 6.68 s (1H); 7.22 s (1H); 7.40-7-62 m (10H)) is alkylated according to the general prescription for operation 8 with 6-bromohexanoic acid isopropyl ester. 6 - [[5-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexane isopropyl ester is obtained

65858 B1 acid.

D.C. 137-139 ° C and 6 - [[6-hydroxy-1 (4-methylphenyl) -2-phenyl-1H-benzimidazol-5yl] oxy] hexanoic acid isopropyl ester

bp 177-178 ° C

Example 199

6- [[5-Hydroxy-1- (4-methyl phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid was prepared according to general prescription 9.

D.C. 245-248 ° C

Example 200

6 - [[6-Hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid is prepared according to the general prescription 9.

D.C. 182-184 ° C

Example 201

6 - [[5-Methoxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester

6 - [[5-Hydroxy-1 (4-methylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid isopropyl ester is methylated according to general operating instructions 8.

D.C. 89-91 ° C

Example 202

6 - [[5-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is prepared according to general prescription 9.

D.C. Mp 184-186 ° C

Example 203

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

Example 204

6 - [[6-Hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester is prepared analogously to isopropyl ester by alkylation of 5,6-dihydroxy-1 - (4methylphenyl) -2-phenyl-1H-benzimidazole according to the general prescription for operation 8 with 6-bromohexanoic acid methyl ester. 6 - [[5-Hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained

1 H-NMR (CDCl 3: delta = 1.45-1.58 ppm m (2H); 1.65-1.90 m (4H); 2.37 t (J = 7.5 Hz, 2H); 2.48 s (3H); 3.68 s (3H); 3.981 ( J = 7.5 Hz, 2H);

5.68 s (breit) (1H, OH); 6.62 s (1H); 7.18 d (J = 8 Hz, 2H); 7.22-7.38. m (5H); 7.40 s (1H); 7.53 dd (J = 8, 1Hz, 2H) and 6 - [[6-hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester

bp 141-143 ° C

Example 205

6 - [[5-Methoxy-1- (4methylphenyl) -2-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester mg 6 - [[5-methoxy-1- (4-methylphenyl) -2phenyl -1 H-Benzimidazol-6-yl] oxy] hexanoic acid was dissolved in 2 ml of methanol, mixed with 1 drop of conc. sulfuric acid and the mixture was stirred for 2 h. It is mixed with saturated potassium hydrogen carbonate solution, diluted with water, extracted with ethyl acetate, the extract is dried over sodium sulfate and concentrated in vacuo. The residue was crystallized from diisopropyl ether.

D.C. 81-82 ° C

Example 206

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

6 - [[6-Hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-5yl] oxy] hexanoic acid methyl ester is methylated with methyl iodide according to general working order 8.

D.C. 108-110 ° C

Example 207

6 - [[6-Methoxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid is prepared according to general prescription 9.

D.C. 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

65858 B1 was stirred for 7 h at 40 ° C. After cooling, the suction filter was sucked off and the residue was crystallized from ethanol.

1 H-NMR (CDCl ₃ ): δ = 2.20 ppm s (6H);

6.43 s (1H); 6.90-7.0 m (2H); 7.14 d (J = 8 Hz, 1H); 9.08 s (1H); 9.70 s (breit) (1H); 10.2-10.6 (1H)

b) 6 - [[3 - [(3,4-dimethylphenyl) amino] -4,6-dinitrophenyl] oxy] hexanoic acid methyl ester g 3 - [(3,4-dimethylphenyl) amino] -4,6-dinitrophenol O-alkylated analogously to the general prescription for operation 8 with 6bromhexanoic acid methyl ester at 70 ° C.

1 H-NMR (CDCl ₃ ): δ = 1.45-1.88 ppm m (6H); 2.30 s (6H); 2.331 (J = 7.5 Hz, 2H); 3.68 s (3H); 3,881 (J = 7.5 Hz, 2H); 6.45 s (1H); 7,007.08 m (2H); 7.25 d (J = 8 Hz, 1H); 9.03 s (1H); 9.89s (Breit) (IH)

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 prescription 1. 500 mg of the crude product are converted with benzimidate hydrochloride according to general prescription 4. Unlike general prescription 4, the crude product is not washed with aqueous hydrochloric acid after absorption in a solvent.

1 H-NMR (CDCl ₃ ): δ = 1.48-1.58 ppm m (2H); 1.62-1.78 m (2H); 1.78-1.90 m (2H); 2.30 s (3H); 2.38 s (3H); 2,381 (J = 7.5 Hz, 2H); 3.67 s (3H); 3.93 t (J = 7.5 Hz, 2H); 6.56 s (1H); 6.987.08 rn (2H); 7.18 s (1H); 7.20-7.32 m (4H); 7.52 dd (J - 8 Hz and 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 converted with 4-chlorobenzenesulfonic acid chloride according to general prescription 13.

D.C. 186-191 ° C

Example 210

6 - [(5-Amino-2- (4-fluorophenyl) -1- (4-methoxyphenyl) -1H-benzimidazol-6yl) oxy] hexanoic acid methyl ester is prepared analogously to 6- [(5 - amino-1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid.

MS (EI): 477 (molecular peak)

Example 211

6 - [(5-Amino-1- (4-methoxyphenyl) -2- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester was prepared analogously to 6 - [(5-amino1- ( 3,4-Dimethylphenyl) -2-phenyl-1H-benzimidosol-6-yl) oxy] hexanoic acid

MS (EI): 489 (molecular peak)

Example 212

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -2- (4-fluorophenyl) -1- (4methoxyphenyl) -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 converted with 4-chlorobenzenesulfonic acid chloride according to the general regulation to work 13.

Mp 180-182 ° C

Example 213

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2- (4methoxyphenyl) -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 converted according to the general prescription of 13 with chloride of 4 -chlorobenzenesulfonic acid.

D.C. 169-171 ° C

Example 214

4 - [(5-Amino-1- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] butanoic acid methyl ester was prepared analogously to 6 - [(5-amino-1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid.

1 H-NMR (CDCl ₃ ): δ = 2.17 ppm tt (J = 8 u. 8 Hz, 2H); 2.521 (J = 8 Hz, 2H); 3.68 s (3H); 3.90 s (3H); 3.98 t (J = 7.5 Hz, 2H); 6.54 s (1H);

65858 Bl

7.0 d (J = 12 Hz, 2H); 7.18-7.35 m (6H); 7.50-7.58 m (2H).

Example 215

4 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] butanoic acid methyl ester

4 - [(5-Amino-1- (4-methoxyphenyl-2-phenyl-1H-benzimidazol-6-yl) oxy] butanoic acid methyl ester is converted according to the general prescription for operation 13 with 4chlorobenzenesulfonic acid chloride.

MS (EI): 605 (molecular peak)

Example 216

5 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester was prepared analogously to 6 - [(5-amino-1 (3 , 4-dimethylphenyl) -2-phenyl-1H-benzimidazol6-yl) oxy] hexanoic acid.

1 H-NMR (CDCl ₃ ): δ = 1.78-1.89 ppmm (4H); 2.321 (J = 8 Hz, 2H); 3.68 s (3H); 3.88 s (3H); 3.92 t (J = 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- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester is converted with 4-chlorobenzenesulfonic acid chloride according to the general prescription 13.

MS (EI): 619 (molecular peak)

Example 218

6 - [(5-Amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidizol-6-yl) oxy] hexanoic acid methyl ester is prepared analogously to 6 - [(5-amino- 1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid.

D.C. 129-131 ° 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- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is converted according to the general prescription for operation 13 with 4chlorobenzenesulfonic acid chloride.

D.C. Mp 168-170 ° C

Example 220

6 - [[5 - [[(chlorophenyl) sulfonyl] amino] -1 (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid was prepared according to general prescription 9.

D.C. 181-182 ° C

Example 221

6 - [(5-amino-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is prepared analogously to 6 - [(5-amino- 1- (3,4-Dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid.

D.C. 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 is converted with 4-chlorobenzenesulfonic acid chloride according to general prescription 13 .

D.C. 189-191 ° C

Example 223

6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] 1- (4-methylphenyl) -2-1H-benzimidazol-6-yl] oxy] hexanoic acid was prepared according to general operating instructions 9.

D.C. 102-105 ° C

Example 224

5 - [(5-Amino-1,2-diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester was prepared analogously to 6 - [(5-amino1 - (3,4-dimethylphenyl) -2 -phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid

1 H-NMR (CDCl ₃ ): δ = 1.82-1.95 ppm m (4H); 2.39 t (J = 8 Hz, 2H); 3.69 s (3H); 3,924.00 m (2H); 6.60 s (1H); 7.26-7.34 m (6H); 7,437.58 m (5H).

Example 225

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

5 - [(5-amino-1,2-dife. Methyl ester

65858 Bl-Nyl-1H-benzimidazol-6-yl) oxy] pentanoic acid is converted according to the general prescription for operation 13 with 4-chlorobenzenesulfonic acid chloride.

D.C. Mp 157-161 ° C

Example 226

5- [[5 - [[(chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid was prepared according to general prescription 9.

D.C. 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- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is converted according to the general prescription for operation 13 with 4-fluorobenzenesulfonic acid chloride.

MS (EI): 617 (molecular peak)

Example 228

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

6 - [(5-Amino-1- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester is converted according to the general prescription for operation 13 with 4- (trifluoromethyl) chloride benzenesulfonic acid.

MS (EI): 668 (molecular peak)

Example 229

6- [[5 - [[(4-Trifluorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid are prepared according to general prescription 9 .

D.C. 190-192 ° C

Example 230

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

6 - [[5 - [[(4-Chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) 2-1 H-benzimidazol-6-yl] oxy] hexanoic acid 100 mg was dissolved in 3 ml. tetrahydrofuran. At 0 ° C, 10 mg of sodium hydride was added, stirred for 30 min, 50 µl of methyl iodide were added dropwise while stirring for another 60 min at 0 ° C. It is combined with saturated ammonium chloride solution, extracted three times with ethyl acetate, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel.

D.C. 178-180 ° C

Example 231

[[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] oxy] acetic acid methyl ester

100 mg of 4-χπορ-N- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide are suspended in 0.5 ml of N, N-dimethylformamide, mixed with 8 mg of sodium hydride and stirred for 8 hours. 30 min at 20 ° C. 50 mg of bromoacetic acid methyl ester was added, stirred for 15 h, mixed with water, extracted three times with ethyl acetate, the extract dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

1 H-NMR (CDCl 3: delta = 3.70 ppm s (3H); 4.52 s (2H); 7.20 d (J = 8 Hz, 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 was prepared according to general prescription 9.

D.C. 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 are suspended in 0.5 ml of N, N-dimethylformamide, mixed with 6 mg of sodium hydride and stirred for 6 hours. 30 min at 20 ° C. 56 mg of 4-bromobutyric acid methyl ester was added, stirred for 15 h, mixed with water, extracted three times with ethyl acetate, the extract dried over sodium sulfate, concentrated in vacuo and the residue was digested with diisopropyl ester.

D.C. 54-58 ° C

Example 234

65858 Bl

4- [[(4-chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] butanoic acid was prepared according to general prescription 9.

D.C. Mp 249-254 ° C

Example 235

5 - [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] pentanoic acid methyl ester

100 mg of 4-chloro-L- (1,2-diphenyl-1H-benzimidazol-5-yl) benzenesulfonamide were suspended in 0.5 ml of N, N-dimethylformamide, mixed with 8 mg of sodium hydride and stirred for 30 min. at 20 ° C. 60 mg of 5-bromoheptanoic acid methyl ester was added, stirred for 15 h, mixed with water, the extract was dried over sodium sulfate, concentrated in vacuo and the residue was chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 1.46-1.54 ppm m (2H); 1.62-1.78 m (2H); 2.301 (J = 8 Hz, 2H); 3.62 s (3H); 3.621 (J = 8 Hz, 2H); 7.12-7.53 m (17H).

Example 236

5- [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] pentanoic acid was prepared according to general prescription 9.

D.C. 123-127 ° C

Example 237

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

6 - [[1,2-Diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid methyl ester is converted according to the general prescription for operation 13 with 4-chlorobenzenesulfonic acid chloride.

MS (EI): 588 (molecular peak)

Example 138

7 - [[(4-Chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] pentanoic 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, mixed with 8 mg of sodium hydride and stirred for 30 min at temperature 20 ° C. 7 mg of 7-bromoheptanoic acid methyl ester was added, stirred for 15 h, mixed with water, extracted three times with ethyl acetate, the extract was dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel.

1 H-NMR (CDCl ₃ ): δ = 1.26-1.64 ppm m (8H); 2.271 (J = 8 Hz, 2H); 3.601 (J = 8 Hz, 2H);

3.68 s (3H); 7.12 dd (J = 10.2 Hz, 1H); 7.22 d (J = 10 Hz, 1H); 7.30-7.61 m (15H)

Example 239

7 - [[(4-chlorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] heptanoic acid was prepared according to general prescription 9.

D.C. 172-178 ° C

Example 240

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

4-fluorobenzenesulfonamide

5- Amino-1,2-diphenyl-1H-benzimidazole was converted according to the general prescription for operation 13 with 4-fluorobenzenesulfonic acid chloride.

D.C. 209-214 ° C

Example 241

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

150 mg of (1,2-diphenyl-1H-benzimidazol-5-yl) -4-fluorobenzenesulfonamide are suspended in 0.5 ml of N, N-dimethylformamide, mixed with 12 mg of sodium hydride and stirred for 30 minutes at 20 ° C. 98 mg of 6-bromohexanoic acid methyl ester was added, stirred for 15 min, extracted three times with ethyl acetate, the extract was dried over sodium sulfate, concentrated in vacuo and the residue was chromatographed on silica gel.

D.C. 128-134 ° C

Example 242

6 - [[(4-fluorophenyl) sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid is prepared according to the general prescription 9.

D.C. 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) -H- (1,2-benzyl)

65858 B1 midazol-5-yl) benzenesulfonamide was suspended in 0.5 ml of N, N-dimethylformamide, mixed with 11 mg of sodium hydride and stirred for 30 min at 20 ° C. 88 mg of 6-bromohexanoic acid methyl ester are added, stirred for 15 h, mixed with water, extracted three times with ethyl acetate; dried over sodium sulfate, concentrated in vacuo, and the residue was degassed with diisopropyl ether.

D.C. Mp 159-161 ° C

Example 244

6 - [[[4- (trifluoromethyl) phenyl] sulfonyl] [1,2-diphenyl-1H-benzimidazol-5-yl] amino] hexanoic acid were prepared according to general prescription 9.

D.C. 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

1.43 g (2,4-dinitroanilino) phenol, 500 mg potassium carbonate and 0.32 ml methyl iodide were stirred in 5 ml N, N-dimethylformamide for 2 h at 20 ° C. The mixture was poured into water, extracted three times with ethyl acetate, the extract dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

D.C. 117-127 ° C

b) 5-amino-1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazole (2,4-dinitrophenyl) (4-methoxyphenyl) amine is hydrogenated according to the general prescription for operation 1. The crude product is cyclized according to the general prescription for operation 3 with trimethylorthobenzoate to the benzimidazole derivative.

1 H-NMR (CDCl ₃ ): δ = 3.88 ppm s (3H); 6.70 dd (J = 12.2 Hz, 1H); 6.95-7.06 m (4H); 7,187.38 m (7H); 7.53-7.65 m (2H).

c) 4-χπορ-N- [1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-5-yl] benzenesulfonamide

5-Amino-1- (4-methoxyphenyl) -2-phenyl-1 H -benzimidazole is converted according to the general prescription for working with 4-chlorobenzenesulfonic acid chloride.

D.C. 238-240 ° C

Example 246

6 - [[(4-Chlorophenyl) sulfonyl] [1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-5-yl] amino] hexanoic acid methyl ester mg 4-chloro-b1- [1- (4-Methoxyphenyl) -2phenyl-1H-benzimidazol-5-yl] benzenesulfonamide was suspended in 0.5 ml of dimethylformamide, mixed with 6 mg of sodium hydride and stirred for 30 min at 20 ° C. 44 mg of 6-bromohexanoic acid methyl ester were added, stirred for 15 h, mixed with water, extracted three times with ethyl acetate, the extract dried over sodium sulfate, concentrated in vacuo and the residue chromatographed on silica gel.

MS (EI): 617 (molecular peak).

Example 247

6 - [[(4-chlorophenyl) sulfonyl] [1- (4methoxyphenyl) -2-phenyl-1H-benzimidazol-5yl] amino] hexanoic acid was prepared according to general working order 9.

D.C. 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 is obtained by converting 1,2-diphenyl-6-hydroxy-1H-benzimidazole with 6-bromo-1,1-dimethylhexanenitrile according to general prescription 8.

D.C. 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-1 H -benzimidazol-6-yl) oxy] hexanenitrile were heated in 5 ml of 80% sulfuric acid for 2 h. After cooling, it is poured very carefully into acetic acid, basified to pH 8 with sodium hydroxide, extracted three times with ethyl acetate, the extract dried over sodium hydroxide, and concentrated in vacuo. The residue was chromatographed on silica gel.

D.C. 115-118 ° C

Example 249

8 - [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] octanoic acid methyl ester is obtained by converting 1,2-di

65858 B1 phenyl-6-hydroxy-1H-benzimidazole with 8-bromoctanoic acid methyl ester according to the general prescription 8.

D.C. 92-95 ° C

Example 250

8 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] octanoic acid was prepared according to the general prescription 9.

D.C. 136-140 ° C

Example 251

6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester was prepared analogously to 6 - ((1 - (3,4 -dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

D.C. 81-85 ° C

Example 252

6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is prepared according to general prescription 9.

D.C. 176-180 ° C

Example 253

7 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] heptanoic acid methyl ester was prepared analogously to 6 - ((1 - (3,4 -dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid.

D.C. 92-98 ° C

Example 254

7- [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] heptanoic acid was prepared according to general prescription 9.

D.C. 175-178 ° C

Example 255

6 - ((1- (3-Fluorophenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is prepared analogously to 6 - ((1- (3,4-dimethylphenyl) methyl ester) -2-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid

bp 104-106 ° C

Example 256

6 - [[1- (3-fluorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid is prepared according to general operating instructions 9.

D.C. 149-15PC

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-phenyl-o-phenylenediamine were dissolved in 5 ml of N, N-dimethylformamide, mixed with 346 mg of EEDQ and 234 mg of 4-nitrobenzoic acid, and the mixture was stirred for 5 h at 100 ° C. After cooling, it is mixed with water. The precipitate was filtered off with suction and purified by column chromatography, absorbed in 6 N hydrochloric acid, and heated for 2 h. After cooling, a saturated solution of potassium hydrogen carbonate is added dropwise. The precipitate was sucked off with a suction filter and dried.

D.C. 189-191 ° C

b) 6-hydroxy-2- (4-nitrophenyl) -1-phenyl-1H-benzimidazole is obtained by conversion according to the general prescription for operation 6.

1 H-NMR (D ₆ -DMSO): delta = 6.56 ppm 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 = 10 Hz, 2H); 8.20 d (J = 10 Hz, 2H); 9.55 s (breit) (1H).

c) 6 - (((2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid methyl ester) is obtained by conversion according to general working order 8.

1 H-NMR (CDCl ₃ ): δ = 1.45-1.55 ppm m (2H); 1.62-1.84 m (4H); 2.33 t (J = 8 Hz, 2H);

3.68 s (3H); 3,951 (J = 8 Hz, 2H); 6.67 d (J = 2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7.28-7.38 m (2H); 7.52-7.60 m (3H); 7.71 d (J = 10 Hz, 2H); 7.77 d (J = 10 Hz, 1H); 8.13 d (J = 10 Hz, 2H)

Example 258

6 - [[2- (4-Nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid was prepared according to general operating instructions 9.

D.C. 181-186'C

Example 259

6 - [[1-Phenyl-2- (3pyridinyl) -1H-benzimidazol-6-yl] oxy] hexa methyl ester

65858 B1 new acid is prepared analogously to 6 - [[1-phenyl-2- (4-pyridinyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester

D.C. Mp 159-160 ° C

Example 260

B1- (Cyclopropylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 18.

MS (EI): 469 (molecular peak)

Example 261

N-Isobutoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 18.

MS (EI): 471 (molecular peak)

Example 262

14- (phenylmethoxy) -6- [2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide

To a solution of 17 mg of carbonyldiimidazole in; 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 was added to 1 ml of tetrahydrofuran, stirred for 30 hours. min at 20 ° C and heated for 30 min countercurrently. At 20 ° C, 16 mg of O-benzylhydroxylamine was added and stirred for 20 h. For further processing, ethyl acetate was added, extracted with 2N hydrochloric acid and saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography.

D.C. 145-148 ° C

Example 263

N- (cyclopropylmethoxy) -6- [2-phenyl-1 (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6yl) oxy] hexanamide was prepared analogously to N (phenylmethoxy) -6- [2-phenyl- 1- (3,4,5 trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide.

MS (EI): 559 (molecular peak)

Example 264

N-isobutoxy-6-P-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-6-yl) oxy] hexanamide is prepared analogously to 1 N- (phenylmethoxy) -6- [2 -phenyl-1- (3,4,5-trimethoxyphenyl) 1H-benzimidazol-6-yl] oxy hexanamide.

1 H-NMR (CDCl ₃ ): δ = 0.94 ppm d (J = 8 Hz, 6H); 1.48-2.03 m (7H); 2.05-2.18 m (2H); 3,603.72 m (2H); 3.76 s (6H); 3.90-4.00 m (2H); 3.96 s (3H); 6.50 s (2H); 6.72 d (J = 2 Hz, 1H); 6.95 dd (J = 10.2 Hz, 1H); 7.28-7.38 m (3H); 7.55-7.62 m (2H); 7.74 d (J = 10 Hz, 1H); 8.20 s (breit) (1H)

Example 265

Ν-Η3θπροπΒπ-6 - [(1,2-diphenyl-1H-benzimidazol-16-yl) oxy] hexanamide was prepared according to general prescription 17.

D.C. 107-112 ° C

Example 266

N, N-fHMeTHn-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 17.

D.C. 83-88 ° C

Example 267

6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-pyrrolidin-1-ylhexan-1-one is prepared according to general prescription 17.

D.C. 84-88 ° C

Example 268

N- (2-methoxyethyl) -6 - [(1,2-diphenyl-1 H -benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 17.

D.C. 63-68 ° C

Example 269

N- (3-methoxypropyl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general working order 18.

D.C. 84-91 ° C

Example 270

N-Isobutyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 17.

1 H-NMR (CDCl ₃ ): δ = 0.90 ppm d (J = 8 Hz, 6H); 1.44-1.57 m (2H); 1.65-1.85 m (5H); 2.20 t (J = 8 Hz, 2H); 3.08 t (J = 8 Hz, 2H); 3.94 t (J = 8 Hz, 2H); 6.68 d (J = 2 Hz, 1H); 6.96 dd (J = 10.2 Hz, 1H); 7.25-7.38 m (5H); 7.45-7.58 m (5H); 7.75 d (J = 10 Hz, 1H).

Example 271

65858 Bl

N - [(2,2-dimethylamino) ethyl] -N-methyl-6 [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 17.

1 H-NMR (CDCl ₃ ) (Signal des Hauptrotamer): delta = 1.44-1.57 ppm m (2H); 1.64-1.84 m (4H); 2.30 s (6H); 2.34 t (J = 8 Hz, 2H); 2,471 (J = 8 Hz, 2H); 3.00 s (3H); 3,501 (J = 8 Hz, 2H); 3.941 (J = 8 Hz, 2H); 6.69 d (J = 2 Hz, 1H); 6.96 dd (J = 10.2 Hz, 1H); 7.25-7.36 m (5H); 7,457.56 m (5H); 7.73 d (J = 10 Hz, 1H)

Example 272

N- (2-methoxyethyl) -N-methyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 17.

1 H-NMR (CDCl ₃ ) (Signal des Hauptrotamer): delta = 1.43-1.58 ppm m (2H); 1.63-1.84 m (4H); 2.331 (J = 8 Hz, 2HJ; 3.07 s (3H); 3.32 s (3H); 3.47-3.58 m (4H); 3.951 (J = 8Hz, 2H); 6.70 d (J = 2 Hz, 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, 1H).

Example 273

6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-morpholin-1-ylhexan-1-one is prepared according to general prescription 17.

1 H-NMR (CDCl ₃ ): δ = 1.47-1.59 ppm m (2H); 1.63-1.88 m (4H); 2,341 (J = 8 Hz, 2H); 3,423.49 m (2H); 3.57-3.70 m (6H); 3.941 (J = 8 Hz, 2H);

6.68 d (J = 2 Hz, 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 = 10 Hz, 1H).

Example 274

HH-di (-2-methoxyethyl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 18.

D.C. 88-98 ° C

Example 275

N-isopentyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide was prepared according to general prescription 18.

D.C. 127-129 ° C

Example 276

N- (pyridin-2-yl) -6 - [(1,2-diphenyl-1 H -benzimidazol-6-yl) oxy] hexanamide was prepared according to general working order 18.

D.C. 120-124 ° C

Example 277

Styridin-3-yl) -6 - [(1,2-diphenyl-1 H -benzimidazol-6-yl) oxy] hexanamide is prepared according to general prescription 18.

D.C. 154 ° C

Example 278

6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-piperidin-1-ylhexan-1-one is prepared according to general prescription 18.

D.C. 93-98 ° C

Example 279 [6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-hexanoyl] piperidine-4-carbonamide was prepared according to general prescription 17.

D.C. 177-178 ° C

Example 280

[[6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-hexanoyl] methylamino] acetic acid ethyl ether was prepared according to General Work Prescription 17.

1 H-NMR (CDCl ₃ ) (Signal des Hauptrotamer): delta = 1.23 ppm t (J = 8 Hz, 3H); 1.45-1.88 m (6H); 2.40 t (J = 8 Hz, 2H); 3.08 s (3H); 3.93 t (J = 8 Hz, 2H); 4.12 s (2H); 4.18 q (J = 8 Hz, 2H); 6.70 d (J = 2 Hz, 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 = 10 Hz, 1H).

Example 281

4 - [[6 - [(1,2-diphenyl-1 H -benzimidazol-6-yl) oxy] -1-hexanoyl]] piperazine-1-carboxylic acid ethyl ester was prepared according to general prescription 17.

1 H-NMR (CDCl 3: delta = 1.27 ppm t (J = 8 Hz, 3H); 1.45-1.60 m (2H); 1.63-1.88 m (4H); 2.36 t (J = 8 Hz, 2H); 3.40-3.53 m (6H); 3.56-3.64 m (2H); 3.93 t (J = 8 Hz, 2H); 4.15 q (J = 8 Hz, 2H);

6.69 d (J = 2 Hz, 1H); 6.96 dd (J = 10.2 Hz, 1H); 7.23-7.38 m (5H); 7.45-7.56 m (5H); 7.76 d (J = 10 Hz, 1H).

Example 282

N-isopropyl-6-C 1- (3,4-dimethylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide is prepared according to the general requirement

65858 Workbook 18.

MS (EI): 469 (molecular peak)

Example 283

N, N-dimethyl-6 - [[[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to the general prescription for operation.

MS (EI): 455 (molecular peak)

Example 284

HH-dimethyl-6 - [[[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general working order 18.

MS (EI): 483 (molecular peak)

Example 285

N-Isobutyl-6 - [[1- (3,4-dimethyl phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general working order 18.

1 H-NMR (CDCl ₃ ): δ = 1.42-1.55 ppm m (2H); 1.60-1.88 m (8H); 2.15 t (J = 8 Hz, 2H); 2.28-2.40 m (2H); 2.30 s (3H); 2.35 s (3H); 3.931 (J = 8 Hz, 2H); 4.40 quintett (J = 8 Hz, 2H); 5.55 s (breit) (1H); 6.63 d (J = 2 Hz, 1H); 6.92 dd (J = 10.2 Hz, 1H); 7.03 dd (J = 10 Hz and 2 Hz, 1H); 7.08 d (J = 2 Hz, 1H); 7.20-7.36 m (4H); 7.57 dd (J = 8.2 Hz, 2H); 7.72 d (J = 10 Hz, 1H).

Example 286

N-Cyclopropyl-6 - [[[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general working order 18.

MS (EI): 467 (molecular peak)

Example 287

N-Cyclobutyl-6 - [[1- (3,4-dimethylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general working order 18.

1 H-NMR (CDCl ₃ ): δ = 1.42-1.55 ppm m (2H); 1.60-1.88 m (8H); 2.15 t (J = 8 Hz, 2H); 2.28-2.40 m (2H); 2.30 s (3H); 2.35 s (3H); 3.931 (J = 8 Hz, 2H); 4.40 quintett (J = 8 Hz, 2H); 5.55 s (breit) (1H); 6.63 d (J = 2 Hz, 1H); 6.92 dd (J = 10.2 Hz, 1H); 7.03 dd (J = 10 Hz in. 2 Hz, 1H); 7.08 d (J = 2 Hz, 1H); 7.20-7.36 m (4H); 7.57 dd (J = 8, 2 Hz, 2H); 7.72 d (J = 10 Hz, 1H).

Example 288

N-tert-butyl-6 - [[[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general working order 18.

1 H-NMR (CDCl ₃ ): δ = 1.32 ppm s (9H); 1.42-1.55 m (2H); 1.62-1.82 m (4H); 2.10 t (J = 8 Hz, 2H); 2.30 s (3H); 2.36 s (3H); 3.921 (J = 8 Hz, 2H); 5.23 s (breit) (1H); 6.66 d (J = 2 Hz, 1H); 6.93 dd (J = 10.2 Hz, 1H); 7.02 dd (J = 10 Hz in. 2 Hz, 1H); 7.09 s (breit) (1H); 7.22-7.36 m (4H); 7.56 dd (J = 8, 2 Hz, 2H); 7.73 d (J = 10 Hz, 1H).

Example 289

N) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] 1- (2-methoxymethyl) pyrrolidin-1-ylhexan-1-one is prepared according to the general requirement for work 18.

MS (EI): 467 (molecular peak)

Example 290

N- (3-imidazol-1-ylpropyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl]] oxy hexanamide was prepared according to the general prescription 18.

1 H-NMR (CDCl ₃ ): δ = 1.42-1.53 ppm m (2H); 1.62-2.02 m (6H); 2.17 t (J = 8 Hz, 2H); 2.27 s (3H); 2.34 s (3H); 3.24 q (J = 8 Hz, 2H);

3.92 t (J = 8 Hz, 2H); 3.96 t (J = 8 Hz, 2H); 5.68 s (breit) (1H); 6.63 d (J = 2 Hz, 1H); 6.88-6.95 m (2H); 7.00 dd (J = 10 Hz in. 2 Hz, 1H); 7.04-7.10 m (2H); 7.20-7.36 m (4H); 7.50 s (breit) (1H); 7.53 dd (J = 8.2 Hz, 2H); 7.72 d (J = 10 Hz, 1H).

Example 291

N- (2-pyridin-2-ylethyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general operating instructions 18 .

1 H-NMR (CDCl ₃ ): δ = 1.38-1.52 ppm m (2H); 1.62-1.82 m (4H); 2.15 t (J = 8 Hz, 2H); 2.30 s (3H); 2.35 s (3H); 2.961 (J = 8 Hz, 2H); 3.66 q (J = 8 Hz, 2H); 3.90 t (J = 8 Hz, 2H); 6.48 s (breit) (1H); 6.65 d (J = 2 Hz, 1H); 6.92 dd (J = 10.2 Hz, 1H); 7.00 dd (J = 10 Hz, 2 Hz, 1H); 7.06-7.38 m (7H); 7.53-7.62 m (3H); 7.72 d (J = 10 Hz, 1H); 8.50 d (breit) (J = 6 Hz, 1H).

Example 292

N, N-dimethyl-6 - [[[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general operating instructions 18.

1 H-NMR (CDCl ₃ ): δ = 1.46-1.58 ppm

65858 Bl m (2H); 1.64-1.88 m (4H); 2.32 1 (J = 8 Hz, 2H);

2.93 s (3H); 3.00 s (3H); 3.961 (J = 8 Hz, 2H); 6.65 d (J = 2 Hz, 1H); 7.00 dd (J = 10.2 Hz, 1H); 7,287.36 m (2H); 7.53-7.61 m (3H); 7.70 d (J = 10 Hz, 2H); 7.76 d (J = 8 Hz, 1H); 8.13 d (J = 8 Hz, 2H)

Example 293

N-isopropyl-6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide is prepared according to general working order 18.

D.C. Mp 162-165 ° C

Example 294

N-Isopentyl-6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general operating instructions 18.

D.C. Mp 148-154 ° C

Example 295

N- (3-methoxypropyl) -6 - [[2- (4-nitrophenyl) -1-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to the general prescription 18.

D.C. 104-110 ° C

Example 296

N- (3-methoxypropyl) -6 - [[1- (indan-5-yl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide was prepared according to general prescription 18.

1 H-NMR (CDCl 3: δ = 1.43-1.56 ppm m (2H); 1.62-1.85 m (6H); 2.10-2.23 m (4H); 2.95 t (J = 10 Hz, 2H); 3.001 (J = 10 Hz , 2H); 3.32 s (3H); 3.32-3.40 m (2H); 3.481 (J = 8 Hz, 2H); 3.931 (J = 8 Hz, 2H); 6.03 s (breit) (1H); 6.67 d ( J = 2 Hz, 1H);

6.93 dd (J = 10.2 Hz, 1H); 7.03 dd (J = 10.2 Hz, 1H); 7.12 s (breit) (1H); 7.26-7.35 m (4H); 7.55 dd (J = 10 Hz, 2H); 7.72 d (J = 8 Hz, 1H).

Example 297

6 - [[1- (4-Methylphenyl) -2 (3-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3 methyl ester] - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 3-pyridylcarbavdehyde according to the general prescription 16.

MS (EI): 429 (molecular peak)

Example 298

6 - [[1- (4-Methylphenyl) -2 (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion from 6 - [[4- amino-3 - ((4-methylphenyl) amino) phenyl]) - oxy] hexanoic acid with 4-pyridylcarbaldehyde.

MS (EI): 429 (molecular peak)

Example 299

6 - [[1- (4-Methylphenyl) 2- (2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion from 6 - [[4-amino- 3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 2-thienylcarbaldehyde according to general prescription 16.

MS (EI): 434 (molecular peak)

Example 300

6 - [[1- (4-Methylphenyl) -2- (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino-3 methyl ester] - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 3-thienylcarbaldehyde according to general prescription 16.

MS (EI): 434 (molecular peak)

Example 301

6 - [[2- (3-indolyl) -1- (4methylphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino- 3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 3-indolylcarbaldehyde according to general prescription 16.

MS (EI): 467 (molecular peak)

Example 302

6 - [[1- (4-methylphenyl) 2- (2-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4-amino- 3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 2-furylcarbaldehyde according to general prescription 16.

MS (EI): 418 (molecular peak)

Example 303

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

65858 B1 is prepared by the conversion of 6 - [[4-amino-3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid methyl ester with 3-furylcarbaldehyde according to general prescription 16.

MS (EI): 418 (molecular peak)

Example 304

6 - [[1- (methylphenyl) -2 (5-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4- amino-3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 5-methyl-2-thienyl-carbaldehyde according to general prescription 16.

MS (EI): 448 (molecular peak)

Example 305

6 - [[1- (4-Methylphenyl) 2- (4-bromo-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6- [methyl ester] [4-Amino-3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 4-bromo-2-thienylcarbaldehyde according to general prescription 16.

MS (EI): 512/514 (molecular peak)

Example 306

6 - [[1- (methylphenyl) -2 (3-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester is obtained by conversion of 6 - [[4- amino-3 - ((4-methylphenyl) amino) phenyl] -oxy] hexanoic acid with 3-methyl-2-thienylcarbaldehyde according to general prescription 16.

MS (EI): 448 (molecular peak)

Example 307

Retention of Microglia Activation To obtain A [beta] -activated microglia in vitro, primary microglia are incubated in rats with a synthetic A [beta] peptide:

To simulate A [beta] accumulation, dry a synthetic A [beta] peptide on a perforated plate - 96. The basic peptide solution of 2 mg / ml water is diluted 1:50 with water. To cover the 96 plate, 30 microl of this diluted peptide solution / aperture was placed and dried at room temperature overnight.

Primary microglia from rats are secreted (harvested) from mixed gliacultures that are formed from the P3 brains of rats. To obtain mixed cultures, the brains of rats were removed at 3 days of age by removing the cerebral cortex. Cell division was performed by trypsinization (0.25% sodium trypsin solution, 15 min at 37 ° C). After separation from non-included tissue fragments using 40 µm Nylonnetz, isolated cells were removed by filtration (800 rpm / 10 min). The cell granules were resuspended in the culture medium and transferred with 100 ml tissue culture vials (1 brain / 1 tissue culture vial). Cell cultivation was performed within 5-7 days in Dulbeccos modified Eagle medium (DMEM, with glutamine), further modified with Penicillin (50 U / ml) and 10% (v / v) calving serum (FCS) at 37 ° C and 5% CO ₂ . During this incubation, an adhesive cell coating consisting mainly of astrocytes is formed. Microglia were produced as non-adhesive or weakly adhesive cells on astrocytes and were removed by shaking incubation (420 rpm, 1h).

For the activation of microglia by Abetapeptide, 2.5 times 10 ⁴ microglia / aperture of Abeta-coated tissue plates were seeded 2.5 times and incubated for 7 days in DMEM (is gelatin), additionally with Peniccillin (50 U / ml), Streptomycin (40 µg / ml) and 10% (v / v) calving serum (FCS) at 37 ° C and 5% CO ₂ . On the fifth day, one compound of the invention was added at different concentrations (0,1,0,3 1,3 and 10 µM).

To assess the reactivity of microglia at day 7 of cultivation, the metabolic activity was measured by reducing MTS (3 (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (sulfophenyl) -2H- tetrazoline), Owen's Reagenz, Baltrop, JA et al. Bioorg. & Med. Lett 1,6111 (1991). The inhibition rate refers to the control treated with DMSO only. The compounds of the invention inhibit microglia activation.

Example 308

Cerebral cerebral infarction in rats (ICAO model)

Compounds of the invention are tested in a cerebral specimen of an animal

65858 Bl chemistry (shock), in the ICAO model (permanent midle cerebral artery occlusion), for in vivo activity. By unilateral closure of the middle cerebral artery (MSA), a cerebral infarction is triggered, which is based on the reduced supply of oxygen and nutrients to the respective cerebral region. The result of this reduced supply is a marked cell death, a strong activation of microglia. This activation of microglia only reaches its maximum in a few days and can be mastered in a matter of weeks. The compounds of the invention are administered intraperitoneally 1-6 days after occlusion to test the substances. On day 7, the animals were perfused and killed. The degree of activation of microglia is measured by a modified immunohistochemical method. To do this, they incubate with fixed-brain Vibratom antibody antibodies, recognizing the antibodies on activated microglia CR3 additional receptors and the MNSP complex, respectively. The quantification of primary antibody formation is performed by an enzyme-linked detection system. Treatment with the compounds of the invention leads to a significant decrease in the activation of microglia in cerebral infectious brain regions. The reduction is at least 20%.

Example 309

Activation of macrophages

LPS-activated THP-1 cells were plated to test substances on macrophages / monocytes. For this purpose, 2.5 x 106 cells / ml were placed in RPMI medium (RPMI 1640 + 10% FCS). The compounds of the invention were pre-incubated at 5 µM for 30 min. The stimulation of the cells was performed at 37 ° C overnight at a concentration of 1 µg / ml LPS. The medium is then harvested and the amount of TNF2 is quantified. Treatment of the cells with the compounds of the invention results in a reduction in the amount of TNF _x at least 30%.

Claims (24)

Claims 1. Benzimidazoles of the general formula wherein R 'represents a mono- or bicyclic C ₆₁₂ alkyl group or one mono- or bicyclic 5-10 membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of N, S or O, such aryl or heteroaryl groups may be replaced by up to three of the following substituents independently of each other: F, Cl, Br, I, 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 , XSO2R ⁴ , so2nh ₂ , SO ₂ NHR ⁴ , SO ₂ NR ⁴ R ⁴ ', NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ 'tXNHSO2R ⁴ , XN (SO2R ⁴ ) SO2R ⁴ ', XNR ⁴ SO2R ⁴ ', XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2,5-dioxypyrrol-1-yl, 2,5-dihydro-2,5-dioxypyrrol-1-yl, 2,7-dihydro2,7-dioxyisoindol-1-yl, R ⁴ , as two of the substituents on R ¹ , when in ortho position with respect to each other, can thus be coupled to each other to form together methanediylbisoxy, ethane-1,2diylbisoxy, propane-1,3-diyl, butane- 1,4-diyl, R ² means one mono- or bicyclic C ₆₁₀ -aryl group or one mono- or bicyclic 5-10 membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of N, S or O, such as the aryl or heteroaryl group indicated groups may be substituted by up to three of the following substituents independently of each other: F, Cl, Br, I, ΧΟΗ, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , 65858 Bl 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 , XSOJR ⁴ , SO, NH ,, SO, NHR ⁴ , SO2NR ⁴ R ⁴ ', no ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', xnhso2r ⁴ , XN (SO2R ⁴ ) so2r ⁴ ', XNR ⁴ SO2R ⁴ ', tetrahydro-2,5-dioxopyrrol-1-yl, 2,5-dihydro-2,5 -dioxypyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, R ⁴ , as two of the substituents on R ² , when orthoed to each other, can thus be bonded to each other such that together to form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane- 1.4-diyl, R ³ means one or two substituents which independently mean: hydrogen, F, Cl, Br, I, HON, 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 ',' NO _2j XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', xnhso2r ⁴ , xnr ⁴ so2r ⁴¹ , 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 , as two of the substituents on R ³ , when orthoed to each other, can thus be coupled to each other to form together methandylbisoxy, ethane-1,2-diylbisoxy, propane-1,3- diyl, butane- 1.4-diyl; R ⁴ u R ⁴ 'independently of one another represent C _m perfluoroalkyl, C _w alkyl, _m -alkenyl, C _{2 6} alkynyl, C _{3 7} cycloalkyl, _{(C] -C3 alkyl-C3. 7} cycloalkyl) C ₁₃ alkyl C ₆₁₀ aryl, C 5-10 alkyl _yz-membered heteroaryl with 1-4 nitrogen, sulfur or oxygen atom, C ₆₁₀ aryl or 5-10 membered heteroaryl with 1-4 nitrogen, sulfur or oxygen atoms, wherein the aryl and heteroaryl groups may be substituted by one or two substituents of the group consisting of F, Cl, Br, CH ₃ , C ₂ H ₅ , NF ₂ , OCH ₃ , OC ₂ H ₂ , CF ₃ , C ₂ F ₅ or may have one annealed methandylylbisoxy-, ethane 1,2,2-diylbisoxy group, and in one 5-membered a cycloalkyl ring one member of the ring may be one nitrogen or one oxygen, and in a 6- or 7-membered cycloalkyl ring one or two of the ring members may be nitrogen and / or oxygen, such as ring nitrogen, in a given may be substituted with C ₁₃ alkyl or C _3-6 alkanoyl, R ⁵ and R ⁵ 'represent, independently of one another, C _m alkyl, C _{2 6} alkenyl, C _{2 6} alkynyl, having one carbon atom can be replaced by 0, S, SO, S0 _2, NH, N Cj_ ₃ alkyl, or N With ₁₃ alkanoyl, C _3-7 cycloalkyl - C _1-4 alkyl, wherein in one 5-membered cycloalkyl ring one member of the ring may be nitrogen or oxygen and in one 6- or 7-membered cycloalkyl ring one or two of the members of the ring may be nitrogen and / or oxygen, the ring nitrogens, optionally, may be substituted with _C13 alkyl or _C13 alkanoyl, C ₆ _ ₁₀ aryl or 5-10 membered heteroaryl can be substituted with 1-4 heteroatoms from N, S and oxygen, wherein said alkyd, alkenyl, and alkynyl chains may be substituted with the above-mentioned cycloalkyl, and or or heteroaryl, such as the aforementioned alkyl and cycloalkyl radicals may be substituted by up to two substituents from CF _3, C ₂ F _5, OH, 0C ₁₃ alkyl, NH _2, NH Cj _-C3 alkyl, NHC ,. ₃ alkanoyl, N (C _1-3 alkyl) ₂ , N (C _1-3 alkyl) (C _1-3 alkanoyl), COOH, CONH ₂ , COOC ₃ alkyl and all of the above aryl and heteroaryl groups with one or two substituents in the group consisting of F, Cl, Br, CH ₃ , c ₂ n ₅ , no ₂ , ax ₃ , ax ₂ n ₅ , cf ₃ , c ₂ f _5, or also have one annealed methandylbisoxy-, ethane-1,2-diylbisoxy group, or R ⁵ and R ⁵ 'together with the nitrogen atom form a 5-7 membered heterocycle which may contain another oxygen, nitrogen or sulfur atom and may be substituted by C ₁₄ -alkyl, C ₁ -alkoxy-C ₀₂ -alkyl , With _14- alkoxy-carbonyl, aminocarbonyl or phenyl, A represents Cj_j ₀ alkanediyl, C ₂ alkenediyl, C ₂₁₀ alkindiil, (C ₀₅ alkanediyl-C _3-7 cycloalkanediyl-C _{0 5} alkanediyl), with a 5-membered cycloalkyl ring one of the ring members may be nitrogen or oxygen and 65858 B1 a 6- or 7-membered cycloalkyl ring one or two of the ring members may be nitrogen and / or oxygen, the ring nitrogen being optionally substituted by C ₁₃ alkyl or C ₁₃ alkanoyl, as in the foregoing above aliphatic chains one carbon atom or two carbon atoms can be replaced by Ο, NH, NH ₁₃ alkyl, NC _{] 3} alkanoyl, and the alkyl or cycloalkyl groups can be substituted with up to two substituents of = O, OH. 0C ₁₃ alkyl, NH ₂ , NH C, ₃ alkanoyl, N (C ₁₃ alkyl) ₂ , C 1 -C 6 alkylHC 4 alkanoyl), B means COOH, COOR ⁵ , conh2, conhnh2, CONHR ⁵ , CONR ⁵ R ⁵ ', CONHOH, CONHOR ⁵ , SO3H, SO ₂ N ^, 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 '), tetrazolyl, commonly associated with one carbon of group A, or means the general group YAB represents N (SO ₂ R ⁴ ) (SO ₂ R ⁴ ') or NHSO ₂ R ⁴ , X means one bond, CH ₂ , (0¾ NES (0¾ NES 01 (0¾ ethoxy,), Y stands for O, NH, NR ⁴ , NCOR ⁴ , NSO ₂ R ⁴ , provided that Y represents NH, NR ⁴ , NCOR ⁴ or NSO ₂ R ⁴ , and a) the substituent R ² contains one nitrogen-containing saturated heterocycle, and that heterocycle is not substituted for the imine nitrogen by H, methyl, propyl or isopropyl, or b) optionally, the substituent groups HNHR ⁴ or XNR ⁴ R ⁴ 'of the substituent R ² , R ⁴ and / or R ⁴ ' do not mean that C ₁ -C 6 alkyl, that at the same time B is COOH, SO ₃ H, PO ₃ H ₂ and R ¹ and R ² independently represent C 1-4 heteroaryl or phenyl when they are not independently substituted, simply substituted with C 16 alkyl, C 1-4 perfluoroalkyl, O C 1-4 alkyl, O C 1-4 perfluoroalkyl, COOH, COO C ] C 1-6 alkyl, CO-C 6 alkyl, CONH 2, CONHR ⁴ , NO 2, NH ₂ , NHCOR ⁴ , NHSO ₂ R ^4, or substituted with 1 or 2 halogen atoms of the group F, Cl, Br, J, with the exclusion of the following compounds : [(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) 2phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester 6 - [[1- (4-Nitrophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 5 - [[1- (4-aminophenyl) 2-phenyl] -1H 5 - [[1- [4 - [[(4-chlorophenyl) sulfonyl] amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] -benzimidazol-6-yl] oxypentanoic acid methyl ester] pentanoic acid, 5 - [[1- [4 - [(acetyl) amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester, 5 - [[1- (3-nitrophenic yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid, 6 - [[1- (3-nitrophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester, methyl 5 - [[1- (3-Aminophenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid ester, 5 - [[1- [3 - [[(4-chlorophenyl) sulfonyl] methyl ester ] amino] phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid, 5 - [[1- [3 - [(acetyl) amino] phenyl] -2-phenyl] 1H- benzimidazol-6-yl] oxy] pentanoic acid. Benzimidazoles according to claim 1, characterized in that R ¹ means one mono- or bicyclic C ₆₁₂ aryl group or one mono- or bicyclic 5-10 membered heteroaryl group of 1-2 heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen, such as the indicated aryl or heteroaryl groups may be independently substituted by up to three of the following substituents: F, Cl, Br, HON, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XCN, UNCON, XCOOR ⁴ , 65858 Bl XCONH _r XCONR ⁴ R ⁴ ', xconhr ⁴ , xconhoh, XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', R ⁴ , as two substituents on R ¹ when orthoed to each other, can thus be bonded together so that together to form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl. Benzimidazoles according to claims 1 or 2, characterized in that R ² denotes a mono- 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 groups may be independently substituted by the following substituents: F, C1, Br, HON, 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 , XSO.R ⁴ , SO, NH 'SO, NHR ⁴ , SO ₂ NR ⁴ R ⁴ ', NO ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XN (SO2R ⁴ ), SO2R ⁴ ', XNR ⁴ SO2R ⁴ ', R ⁴ , being two of the substituents on R ² when in ortho position with respect to each other , can thus be bonded together to form methandiylbisoxy, ethane-1,2diylbisoxy, propane-1,3-diyl, butane-1,4-diyl together. Benzimidazoles according to claims 1 to 3, characterized in that R ³ represents one or two substituents which independently represent hydrogen, F, Cl, Br, HON, 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 , XSO2R ⁴ , SO2NH ₂ , ₂ nhr ⁴ , SO ₂ NR ⁴ R ⁴ ', NO ₂ , XNH ₂ , XNHR ⁴ , XNR ⁴ N ⁴ ', XNHSO ₂ R ^4, XNR ⁴ SO2R ⁴ ', XN (SO2R ⁴⁾ so ₂ r ^4', XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , R ⁴ , as two substituents R ³ when orthoed to each other, can thus be bonded together to form methanediylbisoxy, ethane-1,2-diylbisoxy, propane -1,3-diyl, butane-1,4-diyl. Benzimidazoles according to one of Claims 1 to 4, characterized in that R ⁴ u R ⁴ 'independently of one another are CF _3, C ₂ F _5, C _m alkyl, C ₂₄ alkenyl, C _{2 4} alkynyl, C _{3 6} cycloalkyl, (C _{yz alkyl-C3 6} cycloalkyl), phenyl, or 5-6 membered heteroaryl with 1-2 nitrogen, sulfur or oxygen atoms, the phenyl and heteroaryl groups being substituted by one or two substituents in the group consisting of F, Cl, Br, CH ₃ , C ₂ H ₅ , OCC, OC ₂ H_, CF2C4, and in one 5-membered cycloalkyl ring one member of the ring may be one nitrogen or one oxygen and in one 6-membered cycloalkyl ring one or two members of the ring may be nitrogen and / or acidic genus, wherein the ring nitrogen may optionally be substituted by C ₁₃ alkyl or C ₃ alkanoyl. Benzimidazoles according to one of Claims 1 to 5, characterized in that R ⁵ and R ⁵ 'independently of one another denote C ₁₆ alkyl, one carbon atom being substituted by O, NH, N C ₁₃ alkyl, N C _1-3 alkanoyl, C ₃ _ ₇ cycloalkyl-C _{0 3} alkyl, in a 5-membered cycloalkyl ring one ring member can be an N or an O and in a 6- or 7-membered cycloalkyl ring one or two ring members can be N and / or O, wherein the nitrogen from the ring may optionally be substituted by C ₁₃ alkyl or C _1-3 alkanoyl, the said C _1-4 alkyl moieties being substituted by one of the above cycloalkyls or by one 5- A 6-membered heteroatom with 1-2 heteroatoms selected from N, S or O, all of the above alkyl and cycloalkyl moieties being able to b are substituted with up to two CF ₃ , OH, O-C ₁₃ alkyl substituents, and the heteroaryl groups mentioned above may be substituted with one or two substituents F, Cl, CF ₃ , CH ₃ , C ₂ H ₅ , OCH ₃ , OSO or R ⁵ and R ⁵ 'together with the nitrogen atom 65858 Bl is a 5-7 membered heterocycle which may contain another oxygen, nitrogen or sulfur atom and may be substituted by C _1-4 alkyl, C _1-4 alkoxy-C _0-2 alkyl, C _1-4 alkoxycarbonyl, aminocarbonyl, or phenyl. Benzimidazoles according to one of Claims 1 to 6, characterized in that A represents C _1-10 alkanediyl, C ₂₁₀ alkenediyl, C ₂₁₀ alkynediyl, (C _{5 5} alkanediyl-C _{3 7} cycloalkanediyl-C _{0 5} alkanediyl), where in one 5-membered cycloalkyl ring one ring member may be one N or one O and in a 6- or 7-membered cycloalkyl ring one or two of the ring members can be N and / or O, as the ring nitrogens may optionally be substituted with _{C] 3} alkyl or C _yz alkanoyl, such as in the above aliphatic chains, one carbon atom or two carbon atoms may be replaced by O, NH, N-C _1-3 alkyl, N-C alkanoyl. Benzimidazoles according to 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 hhh tetrazolyl, usually bonded to a carbon of group A. Benzimidazoles according to one of Claims 1 to 8, characterized in that X is a bond or methylene. Benzimidazoles according to one of Claims 1 to 9, characterized in that Y is O. Benzimidazoles according to claim 1, comprising: [(1,2-Diphenyl-1H-benzimidazol-6-yl) oxy] acetic acid isopropyl ester 3 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid methyl ester of 2 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] propanoic acid 4- [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] butanoic acid isopropyl ester of 5 - [( 1,2 - diphenyl-1H-benzimidazol-6-yl) oxy] pentanoic acid methyl ester of 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester of 6 - [(1, 2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanoic acid 6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide N-methoxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -hexanamide N- (phenylmethoxy) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -hexanamide B1-hydroxy-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -hexanamide methyl ester of 7 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] heptane 6 - [[3- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[2-phenyl-1- [3- (trifluoromethyl) phenyl] 6 - [[2-phenyl-1- [3 (trifluoromethyl) phenyl] -1H-benzimidazol-6-yl] oxy] hexanoic acid -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6- [- [[1- (3-cyanophenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester] - [[1- (3-cyanophenyl) -2-phenyl] 1- 1H-benzimidazol-6-yl] oxy] hexanoic acid 6- [[1- (3-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[1- (4-cyanophenyl) 2phenyl-1H-benzimidazol-6 6-[[1- (4-cyanophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1- (3-yl] oxy] hexanoic acid isopropyl ester chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (3-chlorophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1- (4-chlorophenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[1- (4-chlorophenyl) -2-phenyl-1H- benzimidazol-6-yl] oxy] hexanoic acid methyl 6- [[1- (3-methylphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[1- ( 3 65858 B1 methylphenyl) -2-phenyl4H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (4-methylphenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl 6 - [[1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid ester 6 - [[1- (3,4-dimethyl phenyl) -2-phenyl-1 H] ester 6 - [[1- (3,5-dimethyl phenyl) -2-phenyl-1 H -benzimide azol-6yl] oxy] hexanoic acid isopropyl ester-6-[[1-benzimidazol-6-yl] oxy] hexanoic acid methyl ester (3,5dimethyl phenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester of nab - [[1- (3-methoxyfo) enyl) 6-[[1- (4-methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid Nab - [[1- (3,4-dimethoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [[1- [3,4- (methylenedioxy) phenyl] methyl ester ] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6- [[1- [3,4- (methylenedioxy) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2-phenyl-1- (3,4-trimethoxyphenyl) methyl ester ) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2-phenyl-1- (3,4,5-trimethoxyphenyl) 1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[2-phenyl-1 (3,4,5 -trimethoxyphenyl) -1H-benzimidazol-6yl] oxy] hexanoic acid 6 - [[1- [4- (1 N, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester acid 6 - [[1- [4- (14, N-dimethylamino) phenyl] -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1-phenyl-2- [ 3 (Trifluoromethyl) -1H-benzimide azol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[2- (3-chlorophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl 6- [2- (3-Chlorophenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid ester 6 - [[2- (4-chlorophenyl) -1phenyl-1H-benzimidazole- 6-yl] oxy] hexanoic acid 6 - [[2- (4-chlorophenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester 6 - [[2- (4-meth phenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2- (4-methylphenyl) -1-phenyl-1H-benzimide azol-6-yl] oxy] hexanoic isopropyl ester 6 - [(1-Phenyl-2- (4-pyridinyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazole) -6-yl) oxy] hexanoic acid isopropyl ester of 6 - [(1,2-diphenyl-5-nitro-1H-benzimidazol-6-yl) oxy] hexanoic acid isopropyl ester of 6 - [[5 - [[(4 -bromophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) cy] methyl lfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl] isopropyl ester -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1,2-diphenyl-5 [[(3-methylphenyl) sulfonyl] amino] -1H-benzimidazol-6-yl] oxy isopropyl ester ] 6 - [[1,2-diphenyl-5 [[(4-methylphenyl) sulfonyl] amino] -1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl ester of 6 - [[1. 2-Diphenyl-5 [[(4-methoxyphenyl) sulfonyl] amino) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1,2-diphenyl-5 [[[(4- t Rifluoromethyl) phenyl] sulfonyl] amino] 1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[[4- (acetyl) isopropyl ester] 65858 B1mino) phenyl] sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[bis (3-chlorophenyl) sulfonyl] amino] -1 isopropyl ester , 2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid isopropyl 6 - ((1,2-diphenyl-5 [(propylsulfonyl) amino] -1H-benzimidazol-6yl] oxy] hexanoic acid) isopropyl 6 - [[5 - [(Benzylsulfonyl) amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 2- (2 - ((1,2-diphenyl-1H-benzimidazole- 6-yl) oxy] ethoxy] acetic acid 3- (2 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] ethoxy] methyl ester 6 - [(4-Acetyl-1- (4-methylphenyl) ethyl ester of 6 - [[1- (3-nitrophenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid -2 - phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[1- (4-methylphenyl) -2phenyl-1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester 6 - [[2-phenyl-1- [4- (thiomethyl) phenyl] -1H-benzimidazol-5-yl] oxy] hexanoic acid 6- [[2-phenyl-1 - [(4-thiomethyl) phenyl] methyl ester ] -1H-Benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2-phenyl-1- (3-thienyl) 1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester 6 - [[2-Phenyl-1- (3-thienyl) 1H-benzimidazol-6-yl] oxy] hexanoic acid ester 4 - ((1,2-diphenyl-1H-benzimidazol-6-yl) ester oxy] hexanoic acid B1- (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 L1-isopropyl-6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -hexanamide 6 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-pyrrolidin-1-ylhexan-1-one methyl ester of 5 - [(5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methylphenyl) -2 methyl ester -Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [(5 - ([(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl ] oxy] hexanoic acid methyl ester of 6 - [[4- (acetyloxy) -1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid methyl ester of 6 - [[4- (hydroxy) ) -1- (4methylphenyl) -2-Phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid 6 - [(4- (hydroxy) -1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - ((7-methyl-1- (4methylphenyl) methyl ester) -2-Phenyl-1H-benzimidazol-6yl] oxy] hexanoic acid. Benzimidazoles according to claim 1, comprising: 6 - [(2-phenyl-1- (3pyridyl) -1H-benzimidazol-5-yl] oxy] hexanoic acid methyl ester 6 - [[2-phenyl-1- (3pyridyl) -1H-benzimidazole] methyl ester 6 - [(2-phenyl-1- (4-pyridyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - [(2- (4-yl) oxy] hexanoic acid methyl ester) fluoro-phenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - ([2- (4-methoxyphenyl) 1-phenyl-1H-benzimidazol-6-yl] oxy] ester] 6 - [[2- (4-Bromophenyl) -1phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [[2- [4- (trifluoromethyl) phenyl] methyl -1-Phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - ((1-phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic methyl ester acid 6 - ((1-Phenyl-2- (benzothien-2-yl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [(5-hydroxy-1 (4-methylphenyl) -2) isopropyl ester -phenyl-1H-benzimidazole-6 65858 B1yl] oxy] hexanoic acid 6 - [[5-hydroxy-1- (4-methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5-methoxy-1- (4methoxyphenyl) -2 6 - [(5-hydroxy-1- (4methylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid-phenyl-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] methyl ester] -1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -2 methyl ester - (4-fluorine phenyl) -1- (4-methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[5 - ([(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) - 2- (4methoxyphenyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 4 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl] H methyl ester 5 - [[5 - [[(4-chlorophenyl) sulfonyl] amino] -1- (4-methoxyphenyl) -2-phenyl] N-benzimidazol-6-yl-benzimidazol-6-yl] oxy] butanoic acid methyl ester ] oxy] pentanoic acid 5 - [(5 - [[(4-chlorophenyl) sulfonyl] amino] -1,2-diphenyl-1H-benzimidazol-6-yl] oxy] pentanoic acid methyl ester a [[5 - [((4- (trifluoromethyl) phenyl) sulfonyl] amino] -1- (4-methoxyphenyl) 2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6- [ [5 - [[(4-chlorophenyl) sulfonyl] methylamino] -1- (4-methoxyphenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - ((1- (indan- 5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (indan-5-yl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6 - ((1- (3-fluorophenyl) -2-phenyl-1H-benzimidazole- 6 - [[2- (4-nitrophenyl) -1 phenyl-1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester of 6 - [(1-phenyl- 6-yl] oxy] hexanoic acid methyl ester 2- (3-pyridinyl) -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-6yl) oxy] hexanamide L1-isobutoxy-6- [2-phenyl-1- (3,4,5-trimethoxyphenyl) -1H-benzimidazol-7-yl) oxy] hexanamide 14- (2-methoxyphenyl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide N- (3-methoxypropyl) -6 - [(1,2-diphenyl1H-benzimidazol-6-yl) oxy] hexanamide N-Isobutyl-6- [1,2-diphenyl-1H-benzimidazol-6-yl] oxy] hexanamide 6 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] -1-morpholin-1-ylhexan-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- (pyridin-2-yl) -6 - ((1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide B1- (pyridin-3-yl) -6 - [(1,2-diphenyl-1H-benzimidazol-6-yl) oxy] hexanamide Ν-Η3θπροπΗΠ-6 - [[1- (3,4-dimethylphenyl) -2phenyl-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-dimethyl phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] hexanamide N-isobutyl-6- [[1- (3,4-dimethylphenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanamide N-cyclopropyl-6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-binimidazol-6-yl] oxy] hexanamide N-Cyclobutyl-6 - [[1- (3,4-dimethylphenyl) 2-phenyl-1H-benzimazol-6-yl] oxy] hexanamide N-TpeT-6ynui-6 - [[1- (3,4-dimethylphenyl) -2phenyl-1H-benzimidazol-6-yl] oxy] hexanamide (R) -6 - [(1- (3,4-dimethyl) phenyl) -2-phenyl-1H-benzimidazol-6-yl] oxy] 1- (2 65858 B1 methoxymethyl) -pyrrolidan-1-ylhexan-1-one N- (3-imidazol-1-yl-propyl) -6 - [[1- (3,4-dimethylphenyl) -2-phenyl-1H-benzimidazol-6yl] oxy] hexanamide N- (2-pyridin-2-ylethyl) -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-methoxyphenyl) methyl ester] 2- (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 methyl ester of 6 - [[1- (4-methylphenyl) -2 (2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ether of 6 - [[1- ( 4 - Methylphenyl) -2 (3-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[2- (3-indolyl) -1- (4methylphenyl) -1H-benzimidazol-6] methyl ester 6 - [[1- (4-m-yl) oxy] hexanoic acid methyl ester ethylphenyl) -2 (2-furyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid 6 - [[1- (4-methylphenyl) -2 (3-furyl) -1H-benzimidazole-6] methyl ester 6 - [[1- (4-methylphenyl) -2 (5-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid methyl ester 6-yl] oxy] hexanoic acid methyl ester - [[1- (4-methylphenyl) -2 (3-methyl-2-thienyl) -1H-benzimidazol-6-yl] oxy] hexanoic acid. Use of a compound according to any one of claims 1 to 12 for the preparation of a medicament for the treatment or prevention of diseases associated with the activation of microglia. A pharmaceutical agent comprising one or more compounds according to one of claims 1 to 12 and one or more carriers. Use of benzimidazoles of general formula II in which R ¹ means one mono- or bicyclic C ₆₁₂ aryl group or one mono- or bicyclic 5-10 membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of N, S or O, as the above aryl or heteroaryl groups may be independently substituted by up to three of the following substituents: F, Cl, Br, I, 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 , SO2NH ₂ , SO ₂ NHR ⁴ , SO2NR ⁴ R ⁴ ', NO2, XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XN (SO2R ⁴ ) (SO2R ⁴ ), XNR ⁴ SO2R ⁴ ', XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , tetrahydro-2.5 -dioxopyrrol-1-yl, 2,5-dihydro-2,5dioxopyrrol-1-yl, 2,7-dihydro-2,7-dioxoisoindol-1-yl, R ⁴ as two substituents on R ¹ when in ortho-positioned to each other, may be so bonded together that they together form methandiylbisoxy, ethane-1,2diylbisoxy, propane-1,3-di , Butane-1,4-diyl, R ² denotes one mono- or bicyclic C ₆₁₀ -aryl group or one mono- or bicyclic 5-10 membered heteroaryl group of 1-4 heteroatoms selected from the group consisting of N, S or O, such as aryl or heteroaryl groups may be independently substituted by up to three of the following substituents: F, Cl, Br, I, 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 , 65858 Bl XSR ⁴ , XSOR ⁴ . XSO2R ⁴ , SO2NH ₂ , SO ₂ NHR ⁴ , so2nr ⁴ r ⁴¹ , no2, xnh ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XN (SO2R ⁴ ) (SO2R ⁴ '), xnr ⁴ so2r 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 , R ⁴ , as two substituents on R ² when orthoed to each other, can thus be coupled to each other to form together methandiylbisoxy, ethane-1,2diylbisoxy, propane-1,3-diyl, butane-1 , 4-diyl, R ³ means one or two substituents which independently mean: H, F, Cl, Br, I, HON, 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, XNHR ⁴ , XNR ⁴ R ⁴ ', XNFISO2R ⁴ , XNR ⁴ SO2R ⁴ ', XN (SO2R 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-dioxoindol-1-yl, R ⁴ as two substituents R ³ , when in an ortho position with each other, can be so connected to each other that together they form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl, R ⁴ and R ⁴ 'independently of one another denote C ₁₄ perfluoroalkyl, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C ₃ . ₇ cycloalkyl, (C ₁₃ alkyl - C ₃₇ cycloalkyl), C ₁₃ alkyl - C ₆₁₀ aryl, C ₁₃ alkyl 5-10 membered heteroaryl with 1-4 N-, S- or O-atoms heteroaryl, C _610- aryl or 5-10 membered heteroaryl having 1-4 N-, S- or O-atoms, the C ₆₁₀ -aryl and heteroaryl groups being substituted by one or two substituents in the group consisting of F, Cl, Br, CC , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ or may also have one annealed methandylbisoxy-, ethane-1,2diylbisoxy group, such as in one 5-membered cycloalkyl ring one the ring member may be one N or one O and in a 6- or 7-membered cycloa kilowatts ring one or two ring members can be N and / or O, as the ring nitrogens may optionally be substituted with C ₁₃ alkyl or C _yz alkanoyl, R ⁵ and R ⁵ ', independently of one another denote hydrogen C ^ alkyl, _m -alkenyl, C _{2 6} alkynyl, having one carbon atom may be replaced by O, S, SO, SO _2, NH, N-Cj .3 alkyl or NC _b3 alkanoyl, C _3-7 cycloalkyl - C ₃ alkyl, wherein in one 5-membered cycloalkyl ring, one ring member may be one N or O and in one 6 or 7-membered cycloalkyl ring one or two ring members may be N and / or O, such as ring nitrogen may optionally be substituted by C ₃ alkyl or ₃ alkanoyl, C ₆₄₀ aryl or 5-10 membered heteroaryl with 1-4 heteroatoms of N, S and O, as indicated above alkyl, alkenyl and alkynyl chains may be substituted by one of the cycloalkyl, aryl or heteroaryl groups mentioned above, all of the above alkyl and cycloalkyl radicals may be substituted by up to two substituents from CF _3, C ₂ F _5, OH, _O-C1-3 alkyl, NH _{2, NH-Cj-C3} alkyl, NH-C ₁₃ alkanoyl, N _(C1-3 alkyl) ₂ , N (C ₃ alkyl) (C ₁₃ alkanoyl), COOH, CONH ₂ , COO C ₃ alkyl and all of the above aryl and heteroaryl groups may be substituted by one or two substituents in the group consisting of F, Cl, Br, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ or also contain an annihilated methandylbisoke-, ethene-1,2diylbisoxy group, or R ⁵ and R ⁵ 'together with the nitrogen atom to form one 5-7 membered heterocycle which may contain another moiety sloroden, nitrogen or sulfur atom and may be substituted with Cj ^ alkyl, _{m-alkoxy-C0 2} -alkyl, C ^ -alkoxycarbonyl, aminocarbonyl or phenyl. A stands for C ₁₁₀ alkanediyl, C ₂₁₀ alkenediyl, C ₂₁₀ alkynediyl, (C ₀₅ alkanediyl-C ₃₇ cycloalkanediyl-C _{0 5} alkanediyl), (Οθ_ ₅ alkanediylaryl-C ₀₅ alkanediyl), ( _C0-5 alkanediyl heteroaryl-C _{0 5} alkanediyl) , wherein in one 5-membered cycloalkyl ring one member of the ring may be one N or one O and in one 6- or 7-membered cycloalkyl ring one or two of the ring members may be N and / or O, such as nitrogen of the ring may optionally be substituted by C ₁₃ -alkyl or C _1-3 -alkanoyl, such that in the above aliphatic chains, one carbon atom or two in the carbon atoms may be replaced by O, NH, NR ⁴ , NCOR ⁴ , NSO ₂ R ⁴ , and alkyl or cycloalkyl groups may be substituted with up to two substitutions 65858 Bl of F, OH, OR ⁴ , OCOR ⁴ , = 0, NH ₂ , NR ⁴ R ⁴ ', NHCOR ⁴ , NHCOOR ⁴ , NHCONHR ⁴ , NHSO, R ⁴ SH, SR ⁴ , B means H, 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 , SO3H, SO ₂ NH ₂ , SO ₂ NHR ⁵ , SO2NR ⁵ R ⁵ ', PO3H, PO (OH) (OR ⁵ ), PO (OR ⁵⁾ ) (OR ⁵ '), PO (OH) (NHR ⁵ ), PO (NHR ⁵ ) (NHR ⁵ ), tetrazolyl, usually bonded to one carbon atom of group A, or represents the general group YAB representing N (SO ₂ R ⁴ ) (SO ₂ R ⁴ ') toihNHSO ₂ R ⁴ , X means one bond, CH ₂ , (0¾ CNS (0¾ 01 (01,0¾ 01 (0¾¾ C ^ CHCCHg)); Y means one bond, O, S, SO, SO ₂ , NH, NR ⁴ , NCOR ⁴ , NSO ₂ R ⁴ , for the preparation of a medicament for the treatment and prevention of diseases associated with the activation of microglia. The use of claim 15, wherein in formula II R ¹ denotes one mono- or bicyclic aryl group or one mono- or bicyclic 510-membered heteroaryl group with 1 -2 heteroatoms selected from the group consisting of N, S or O, the said aryl or heteroaryl group being substituted with up to three of the following substituents independently of each other: F, C1, Br, HON, XOR ⁴ , XOCOR ⁴ , XOCONHR ⁴ , XOCOOR ⁴ , XCOR ⁴ , XCN, XCOOH, XCOOR ⁴ , XC0N1L XCONR ⁴ R ⁴ ', XCONHR ⁴ , XCONHOH XCONHOR ⁴ , XCOSR ⁴ , XSR ⁴ , NO0 ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', R ⁴ , having two substituents on R ¹ when in ortho position to each other can thus be connected to each other such that together form methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1,4-diyl. The use according to claim 15 or 16, wherein in general formula II R ² denotes one mono- or bicyclic aryl group or one mono- or bicyclic 510-membered heteroaryl group of 1 -2 heteroatoms selected from the group consisting of N, S or O, the above-mentioned aryl or heteroaryl groups may be replaced independently by up to three of the following substituents: F, C1, Br, HON, 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 R ⁴ ', XCONHR 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, XNH2, XNHR ⁴ , XNR ⁴ R ⁴ ', XNHS02R ⁴ , XN (SO2R ⁴ ) (SO2R ⁴ '), xnr ^{4 being} ₂ r ⁴ ', XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ , R ⁴ having two substituents on R ² , when in ortho position with each other, can thus be coupled to each other to form together methanediylbisoxy, ethane-1,2-diylbisoxy, propane-1,3-diyl, butane-1, 4-diyl. Use according to one of claims 15 to 17, wherein in the general formula II R ³ means one or two substituents which independently mean: H, F, C1, Br, HON, 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 , XSO2R ⁴ , SO ^ H ,, SO2NHR ⁴ , SO2NR ⁴ R ⁴ ', NO2, XNH ₂ , XNHR ⁴ , XNR ⁴ R ⁴ ', XNHSO2R ⁴ , XNR ⁴ SO2R ⁴ ' , XN (SO2R ⁴ ) (SO2R ⁴¹ ), XNHCOR ⁴ , XNHCOOR ⁴ , XNHCONHR ⁴ or R ⁴ , where the two substituents R ³ , when in ortho position with each other, can be so connected to each other that together form methandiylbisoxy, ethane-1,2-diylbisoke, propane-1,3-diyl, butane 1,4-diyl. The use according to any one of claims 15 to 18, wherein in general formula II R ⁴ and R ⁴ 'independently of one another denote CF ₃ , C ₂ F ₅ , C _1-4 alkyl, C _2-4 alkenyl, C ₂₄ alkynyl, C _3-6 cycloalkyl, (C ₁₃ alkyl-C _3-6 cycloalkyl), C ₁₃ alkylaryl, C ₁₃ alkylheteroaryl, monocyclic aryl or 5-6 membered heteroaryl of 1-2 N-, S- or O-atoms, the aryl and heteroaryl groups being substituted by one or two substituents in the group consisting of F, Cl , Br, CH ₃ , C ₂ H ₅ , NO ₂ , OCH ₃ , OC ₂ H ₅ , CF ₃ , C ₂ F ₅ or have one annealed methandylbisoxy or ethane-1,2diylbisoxy group, and in one 5-membered cycloalkyl ring one of the ring members may be N and / or O, k atoms of nitrogen at a burst 65 858 Bl complexion may optionally be substituted with _{C] 3} alkyl or alkanoyl _yz. The use according to any one of claims 15 to 19, wherein in general formula II R ⁵ and R ⁵ 'independently of one another denote C _1-6 alkyl, with one carbon atom being substituted by O, NH, NC ₁₃ alkyl, NC ₁₃ alkanoyl or C _3-7 cycloalkyl-C 1-6 alkyl, such as in one 5-membered cycloalkyl ring one member of the ring may be one N or one 0 and in one 6- or 7-membered cycloalkyl ring one or two members of the ring may be N and / or 0, the ring nitrogen being optionally may be substituted with _C13 alkyl or _C13 alkanoyl, such as those referred to above C _1-6 alkyl moieties may be substituted by cycloalkyl as defined above or co o a 5-6-membered heteroaromatic with 1-2 heteroatoms selected from the group consisting of N, S or O, all the above alkyl and cycloalkyl moieties may be optionally substituted with up to two substituents from CF _3, OH , O-C ₁₃ alkyl, and the above heteroaryl groups may be substituted by one or two substituents of F, C1, CF ₃ , CH ₃ , C ₂ H ₅ , OOD, or R ⁵ and R ⁵ 'together with the nitrogen atom form a 5-7-membered heterocycle which can contain one oxygen, nitrogen or sulfur atom and may be substituted with C _1-4 alkyl, _m alkoxy - C _0-2 alkyl, _m alkoxycarbonyl, amino carbonyl or phenyl. Use according to any one of claims 15 to 20, wherein in general formula II A is C _1-10 alkanediyl, _C2-10 alkenediyl, _C2-10 alkindiil, (C _{0. 5} alkanediyl - C _{3. 7} cycloalkanediyl-OD alkanediyl) or (Οθ_ ₅ alkanediyl - heteroaryl - C _{o 5} alkanediyl), as an optionally available a heteroaryl group may be substituted by one or two substituents of F, Cl, Br, OD, <OD, ΝΟ ₂ , OOD, OC ₂ H ₅ , CF ₃ , OD, and in another 5-membered cycloalkyl ring one member of the ring may be one N or one O and in a 6- or 7-membered cycloalkyl ring one or two members of the ring may be N and / or O, and the ring nitrogen may optionally be moved to _C13 alkyl or OD alkanoyl, such as in an aliphatic chain of one carbon atom or two carbon atoms may be replaced with 0, NH, NC _{3 3} -alkyl, NC ₁₃ alkanoyl, NSO, -C. ₃ alkyl, and the alkyl or cycloalkyl moieties may be substituted by up to two F atoms or by one of the OH, O-OC alkyl, O-C substituents _{| 3} alkanoyl, = Ο, NH ₂ , NH-OD alkyl, N- (C _{] 3} alkyl) ₂ , NH-C, ₃ alkanoyl, N (OD alkyl) (C ₁₃ alkanoyl), NHCOO OD alkyl, NHCONH OD ₃ alkyl , NHSO ₂ C _1-3 alkyl, SH, S-C _1-3 alkyl. Use according to any one of claims 15 to 21, wherein in general formula II B represents hydrogen, OH, OCOR ⁵ , OCONHR ⁵ , OCOOR ⁵ , COOH, COOR ⁵ , COOD, CONHR ⁵ , CONR'R ⁵ ', CONHOH, CONHOR ⁵ or tetrazolyl, usually bonded to one carbon atom of group A. Use according to one of claims 15 to 22, wherein in the general formula II X stands for single bond or CH ₂ . Use according to any one of claims 15 to 23, wherein in general formula II Y represents a bond, O, S, NH, NR ^4, NCOR ⁴ №ihNSO ₂ R ^4.