# US 2009/0270366 A1 · Benzoimidazole compounds

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- Number: US 2009/0270366 A1
- Document ID: US20090270366A1
- Status: Published application
- Kind: A1
- Application number: 12/229,890
- Filed: 2008-08-26
- Published: 2009-10-29
- Earliest claimed: 2003-09-30
- Assignees: Janssen Pharmaceutica NV
- Inventors: James P. Edwards; Michael D. Hack; David E. Kindrachuk; Jennifer D. Venable
- Web page: https://patentgrep.com/patent/US20090270366A1

## CPC

- C07D 235/18: with aryl radicals directly attached in position 2
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/02: specific for leukemia
- A61P 37/04: Immunostimulants
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C04B 35/632: Organic additives
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 2317/50: characterized by immunoglobulin fragments
- C07K 2317/53: Hinge
- C07K 2318/10: Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C04B: LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE {(roofing granules E04D7/005)}; CERAMICS (devitrified glass-ceramics C03C10/00); REFRACTORIES; TREATMENT OF NATURAL STONE
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

## Claims

### Claim 1

A pharmaceutical composition comprising a therapeutically effective amount of at least one compound selected from compounds of formula (II):
wherein
X is N;
Y is O, NR12, or CR12R13;
Z is CR14;
n is 1;
each of R1-4 is, independently from other substituent assignments, H, C1-4alkyl, C2-5alkenyl, C2-5alkynyl, C3-6cycloalkyl, —C1-4alkoxy, —C1-4alkylamino, —C1-4alkylthio, —C1-4alkylsulfonyl, —OC3-6cycloalkyl, —OCH2Ph, cyano, —CF3, F, Cl, Br, I, nitro, —OCF3, —SCF3, —ORc, —SRc, —S(O)Rc, —SO2Rc, —C(O)Rc, phenyl, benzyl, phenethyl, —C(O)NRaRb, —C(O)ORc, —NRaRb, —CH2NRaRb or —CH2ORc; wherein each of Ra, Rb and Rc is, independently from other substituent assignments, selected from H, C1-4alkyl, C3-6cycloalkyl, phenyl, (C3-6cycloalkyl)C1-2alkyl-, benzyl and phenethyl, or Ra and Rb taken together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring HetCyc1, wherein said ring HetCyc1 has 0 or 1 additional heteroatoms selected from O, S, >NH and >NC1-6alkyl, and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R1-4, Ra, Rb, Rc, and said ring HetCyc1 is optionally, and independently from other substituent assignments, substituted with 1, 2 or 3 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy;
each of R5-7 is, independently from other substituent assignments, H, C1-6alkyl, F, Cl, Br, I, CF3, —OCF3, —ORc, —SRc, —S(O)Rc, —SO2Rc, C1-4alkoxy, cyano, nitro, —C(O)NRaRb, —C(O)phenyl, —C(O)C1-6alkyl, —S(O)C1-4alkyl, or —SO2C1-4alkyl; or, R7 and R6 for a compound of formula (II) taken together with the carbon atoms to which they are attached form a cyclic structure Cyc2 selected from aryl, heteroaryl, 5- or 6-membered carbocycle, and 5- or 6-membered heterocycle with 1 or 2 heteroatoms, wherein said cyclic structure Cyc2 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy;
R8 is H, C1-6alkyl, C1-4alkoxy, or OH;
each of R9 and R10 is, independently from other substituent assignments, H or C1-6alkyl, or R9 and R10 taken together form a 5-6 membered cyclic structure Cyc3, wherein said cyclic structure Cyc3 is a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle with 1 or 2 heteroatoms, and wherein said cyclic structure Cyc3 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy;
R11 is H, C1-4alkyl;
each of R12 and R13 is, independently from other substituent assignments, H or C1-4alkyl; or, when Y is CR12R13, R12 and R13 taken together with the carbon member to which they are attached form an optionally substituted cyclic structure Cyc4, wherein said cyclic structure Cyc4 is a 3- to 6-membered carbocycle or a 3- to 6-membered heterocycle with 0 or 1 additional heteroatoms, or CR12R13 is C═O;
R14 is H, C1-4alkyl, OH, or C1-4alkoxy;
enantiomers, diastereomers, and racemates thereof, pharmaceutically acceptable salts, amides and esters thereof;
provided that:
when Y is O or NR12, then R8 is not OH or C1-4alkoxy; and
neither R1 nor R4 is C(O)NH2.

### Claim 2 (depends on 1)

A pharmaceutical composition as in claim 1, wherein Y is CR12R13.

### Claim 3 (depends on 1)

A pharmaceutical composition as in claim 1, wherein Y is CH2.

### Claim 4 (depends on 1)

A pharmaceutical composition as in claim 1, wherein Z is CH.

### Claim 5 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R1 is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH2OMe.

### Claim 6 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R1 is H, methyl, F, or Cl.

### Claim 7 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R2 is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF3, OCF3, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl.

### Claim 8 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R2 is H, F, Cl, methyl, CF3, OCF3, or t-butyl.

### Claim 9 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R3 is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF3, OCF3, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl.

### Claim 10 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R3 is H, F, Cl, methyl, CF3, OCF3, or t-butyl.

### Claim 11 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R4 is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, R, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH2OMe.

### Claim 12 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R4 is H, methyl, F, or Cl.

### Claim 13 (depends on 1)

A pharmaceutical composition as in claim 1, wherein one or two of R1-4 are not H.

### Claim 14 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R5 is H, F, Cl, methyl, or ethyl.

### Claim 15 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R5 is F, Cl, or methyl.

### Claim 16 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R6 is H, F, Cl, or methyl.

### Claim 17 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R7 is H, F, Cl, or methyl.

### Claim 18 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R8 is H, methyl, or OH.

### Claim 19 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R8 is H.

### Claim 20 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R9 and R10 are, independently, selected from the group consisting of: H, methyl, ethyl, propyl, and isopropyl.

### Claim 21 (depends on 1)

A pharmaceutical composition as in claim 1, wherein each of R9 and R10 is, independently, H or methyl.

### Claim 22 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R11 is H, methyl, or ethyl.

### Claim 23 (depends on 1)

A pharmaceutical composition as in claim 1, wherein R11 is methyl.

### Claim 24

A pharmaceutical composition comprising a therapeutically effective amount of at least one compound selected from the group consisting of:
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-fluoro-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-6-chloro-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,6-dimethyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-chloro-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-tert-butyl-1H-benzoimidazole;
5-tert-Butyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{5-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-fluoro-4-methyl-1H-benzoimidazole;
2-{5-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
4,6-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4-Methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Fluoro-4-methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4-Chloro-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4,5-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
6-Chloro-4-methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Chloro-4-methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-tert-Butyl-2-[2-(4-piperidin-4-yl-butoxy)-pyridin-4-yl]-1H-benzoimidazole;
4,6-Dimethyl-2-[2-(4-piperidin-4-yl-butoxy)-pyridin-4-yl]-1H-benzoimidazole;
2-{2-[4-(1-Ethyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
4,6-Dimethyl-2-{3-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4-Methyl-2-{3-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
6-Chloro-4-methyl-2-{3-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
4-Chloro-2-{3-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-fluoro-4-methyl-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,6-dimethyl-1H-benzoimidazole;
6-Chloro-2-{3-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
5-Chloro-2-{3-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
5-Fluoro-4-methyl-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Chloro-6-fluoro-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-tert-Butyl-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4,5-Dimethyl-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{5-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,6-dimethyl-1H-benzoimidazole;
5-Chloro-2-{5-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Chloro-2-{5-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-6-fluoro-1H-benzoimidazole;
5-tert-Butyl-2-{5-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-chloro-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-chloro-6-fluoro-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-chloro-1H-benzoimidazole;
{4-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-6-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-3-yl}-methanol;
and pharmaceutically acceptable salts of said compounds.

### Claim 25

A pharmaceutical composition for inhibiting leukocyte recruitment in a subject, comprising a therapeutically effective amount of at least one compound selected from compounds of formula (II):
wherein
X is N;
Y is O, NR12, or CR12R13;
Z is CR14;
n is 1;
each of R1-4 is, independently from other substituent assignments, H, C1-4alkyl, C2-5alkenyl, C2-5alkynyl, C3-6cycloalkyl, —C1-4alkoxy, —C1-4alkylamino, —C1-4alkylthio, —C1-4alkylsulfonyl, —OC3-6cycloalkyl, —OCH2Ph, cyano, —CF3, F, Cl, Br, I, nitro, —OCF3, —SCF3, —ORc, —SRc, —S(O)Rc, —SO2Rc, —C(O)Rc, phenyl, benzyl, phenethyl, —C(O)NRaRb, —C(O)ORc, —NRaRb, —CH2NRaRb or —CH2ORc; wherein each of Ra, Rb and Rc is, independently from other substituent assignments, selected from H, C1-4alkyl, C3-6cycloalkyl, phenyl, (C3-6cycloalkyl)C1-2alkyl-, benzyl and phenethyl, or Ra and Rb taken together with the nitrogen to which they are attached, form a 4-7 membered heterocyclic ring HetCyc1, wherein said ring HetCyc1 has 0 or 1 additional heteroatoms selected from O, S, >NH and >NC1-6alkyl, and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R1-4, Ra, Rb, Rc, and said ring HetCyc1 is optionally, and independently from other substituent assignments, substituted with 1, 2 or 3 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy;
each of R5-7 is, independently from other substituent assignments, H, C1-6alkyl, F, Cl, Br, I, CF3, —OCF3, —ORc, —SRc, —S(O)Rc, —SO2Rc, C1-4alkoxy, cyano, nitro, —C(O)NRaRb, —C(O)phenyl, —C(O)C1-6alkyl, —S(O)C1-4alkyl, or —SO2C1-4alkyl; or, R7 and R6 for a compound of formula (II) taken together with the carbon atoms to which they are attached form a cyclic structure Cyc2 selected from aryl, heteroaryl, 5- or 6-membered carbocycle, and 5- or 6-membered heterocycle with 1 or 2 heteroatoms, wherein said cyclic structure Cyc2 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy;
R8 is H, C1-6alkyl, C1-4alkoxy, or OH;
each of R9 and R10 is, independently from other substituent assignments, H or C1-6alkyl, or R9 and R10 taken together form a 5-6 membered cyclic structure Cyc3, wherein said cyclic structure Cyc3 is a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle with 1 or 2 heteroatoms, and wherein said cyclic structure Cyc3 is, independently from other substituent assignments, substituted with 0, 1, or 2 substituents selected from C1-3alkyl, halo, hydroxy, amino, and C1-3alkoxy;
R11 is H, C1-4alkyl;
each of R12 and R13 is, independently from other substituent assignments, H or C1-4alkyl; or, when Y is CR12R13, R12 and R13 taken together with the carbon member to which they are attached form an optionally substituted cyclic structure Cyc4, wherein said cyclic structure Cyc4 is a 3- to 6-membered carbocycle or a 3- to 6-membered heterocycle with 0 or 1 additional heteroatoms, or CR12R13 is C═O;
R14 is H, C1-4alkyl, OH, or C1-4alkoxy;
enantiomers, diastereomers, and racemates thereof, pharmaceutically acceptable salts, amides and esters thereof;
provided that:
when Y is O or NR12, then R8 is not OH or C1-4alkoxy; and
neither R1 nor R4 is C(O)NH2.

### Claim 26 (depends on 25)

A pharmaceutical composition as in claim 25, wherein Y is CR12R13.

### Claim 27 (depends on 25)

A pharmaceutical composition as in claim 25, wherein Y is CH2.

### Claim 28 (depends on 25)

A pharmaceutical composition as in claim 25, wherein Z is CH.

### Claim 29 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R1 is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH2OMe.

### Claim 30 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R1 is H, methyl, F, or Cl.

### Claim 31 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R2 is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF3, OCF3, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl.

### Claim 32 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R2 is H, F, Cl, methyl, CF3, OCF3, or t-butyl.

### Claim 33 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R3 is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF3, OCF3, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl.

### Claim 34 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R3 is H, F, Cl, methyl, CF3, OCF3, or t-butyl.

### Claim 35 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R4 is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, R, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH2OMe.

### Claim 36 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R4 is H, methyl, F, or Cl.

### Claim 37 (depends on 25)

A pharmaceutical composition as in claim 25, wherein one or two of R1-4 are not H.

### Claim 38 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R5 is H, F, Cl, methyl, or ethyl.

### Claim 39 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R5 is F, Cl, or methyl.

### Claim 40 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R6 is H, F, Cl, or methyl.

### Claim 41 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R7 is H, F, Cl, or methyl.

### Claim 42 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R8 is H, methyl, or OH.

### Claim 43 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R8 is H.

### Claim 44 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R9 and R10 are, independently, selected from the group consisting of: H, methyl, ethyl, propyl, and isopropyl.

### Claim 45 (depends on 25)

A pharmaceutical composition as in claim 25, wherein each of R9 and R10 is, independently, H or methyl.

### Claim 46 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R11 is H, methyl, or ethyl.

### Claim 47 (depends on 25)

A pharmaceutical composition as in claim 25, wherein R11 is methyl.

### Claim 48

A pharmaceutical composition comprising a therapeutically effective amount of at least one compound selected from the group consisting of:
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-fluoro-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-6-chloro-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,6-dimethyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-chloro-4-methyl-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-tert-butyl-1H-benzoimidazole;
5-tert-Butyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{5-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-fluoro-4-methyl-1H-benzoimidazole;
2-{5-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
4,6-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4-Methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Fluoro-4-methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4-Chloro-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4,5-Dimethyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
6-Chloro-4-methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Chloro-4-methyl-2-{2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-tert-Butyl-2-[2-(4-piperidin-4-yl-butoxy)-pyridin-4-yl]-1H-benzoimidazole;
4,6-Dimethyl-2-[2-(4-piperidin-4-yl-butoxy)-pyridin-4-yl]-1H-benzoimidazole;
2-{2-[4-(1-Ethyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
4,6-Dimethyl-2-{3-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4-Methyl-2-{3-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
6-Chloro-4-methyl-2-{3-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,5-dimethyl-1H-benzoimidazole;
4-Chloro-2-{3-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-fluoro-4-methyl-1H-benzoimidazole;
2-{3-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,6-dimethyl-1H-benzoimidazole;
6-Chloro-2-{3-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
5-Chloro-2-{3-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-methyl-1H-benzoimidazole;
5-Fluoro-4-methyl-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Chloro-6-fluoro-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-tert-Butyl-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
4,5-Dimethyl-2-{5-methyl-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{5-Chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4,6-dimethyl-1H-benzoimidazole;
5-Chloro-2-{5-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
5-Chloro-2-{5-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-6-fluoro-1H-benzoimidazole;
5-tert-Butyl-2-{5-chloro-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-4-chloro-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-chloro-6-fluoro-1H-benzoimidazole;
2-{5-Bromo-2-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-4-yl}-5-chloro-1H-benzoimidazole;
{4-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-6-[4-(1-methyl-piperidin-4-yl)-butoxy]-pyridin-3-yl}-methanol;
and pharmaceutically acceptable salts of said compounds.