US2009247508A1PendingUtilityA1

Benzoimidazole Compounds

Assignee: EDWARDS JAMES PPriority: Sep 30, 2003Filed: Oct 23, 2008Published: Oct 1, 2009
Est. expirySep 30, 2023(expired)· nominal 20-yr term from priority
A61P 37/08A61P 35/02A61P 37/04C07K 16/00C07K 2318/10C07K 2317/50C07D 401/12A61P 29/00C04B 35/632C07D 401/04C07D 235/18C07D 403/12C07D 401/14C07K 2317/53
67
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Claims

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

exact text as granted — not AI-modified
1 . A method for modulating an H 4  receptor, comprising exposing an H 4  receptor to at least one chemical entity selected from compounds of formula (II), enantiomers, diastereomers, and racemates thereof, pharmaceutically acceptable salts, amides and esters thereof, 
       
         
           
           
               
               
           
         
       
       wherein
 X is N; 
 Y is O, NR 12 , or CR 12 R 13 ; 
 Z is CR 14 ; 
 n is 1; 
 each of R 1-4  is, independently from other substituent assignments, H, C 1-4 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, C 3-6 cycloalkyl, —C 1-4 alkoxy, —C 1-4 alkylamino, —C 1-4 alkylthio, —C 1-4 alkylsulfonyl, —OC 3-6 cycloalkyl, —OCH 2 Ph, cyano, —CF 3 , F, Cl, Br, I, nitro, —OCF 3 , —SCF 3 , —OR c , —SR c , —S(O)R c , —SO 2 R c , —C(O)R c , phenyl, benzyl, phenethyl, —C(O)NR a R b , —C(O)OR c , —NR a R b , —CH 2 NR a R b  or —CH 2 OR c ; wherein each of R a , R b  and R c  is, independently from other substituent assignments, selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, (C 3-6 cycloalkyl)C 1-2 alkyl-, benzyl and phenethyl, or R a  and R b  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 >NC 1-6 alkyl, and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R 1-4 , R a , R b , R c , and said ring HetCyc1 is optionally, and independently from other substituent assignments, substituted with 1, 2 or 3 substituents selected from C 1-3 alkyl, halo, hydroxy, amino, and C 1-3 alkoxy; 
 each of R 5-7  is, independently from other substituent assignments, H, C 1-6 alkyl, F, Cl, Br, I, CF 3 , —OCF 3 , —OR c , —SR c , —S(O)R c , —SO 2 R c , C 1-4 alkoxy, cyano, nitro, —C(O)NR a R b , —C(O)phenyl, —C(O)C 1-6 alkyl, —S(O)C 1-4 alkyl, or —SO 2 C 1-4 alkyl; or, R 7  and R 6  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 C 1-3 alkyl, halo, hydroxy, amino, and C 1-3 alkoxy; 
 R 8  is H, C 1-6 alkyl, C 1-4 alkoxy, or OH; 
 each of R 9  and R 10  is, independently from other substituent assignments, H or C 1-6 alkyl, or R 9  and R 10  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 C 1-3 alkyl, halo, hydroxy, amino, and C 1-3 alkoxy; 
 R 11  is H, C 1-4 alkyl; 
 each of R 12  and R 13  is, independently from other substituent assignments, H or C 1-4 alkyl; or, when Y is CR 12 R 13 , R 12  and R 13  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 CR 12 R 13  is C═O; 
 R 14  is H, C 1-4 alkyl, OH, or C 1-4 alkoxy; 
 
       provided that:
 when Y is O or NR 12 , then R 3  is not OH or C 1-4 alkoxy; and 
 neither R 1  nor R 4  is C(O)NH 2 . 
 
     
     
         2 . A method as in  claim 1 , wherein Y is CR 12 R 13 . 
     
     
         3 . A method as in  claim 1 , wherein Y is CH 2 . 
     
     
         4 . A method as in  claim 1 , wherein Z is CH. 
     
     
         5 . A method as in  claim 1 , wherein R 1  is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH 2 OMe. 
     
     
         6 . A method as in  claim 1 , wherein R 1  is H, methyl, F, or Cl. 
     
     
         7 . A method as in  claim 1 , wherein R 2  is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF 3 , OCF 3 , F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl. 
     
     
         8 . A method as in  claim 1 , wherein R 2  is H, F, Cl, methyl, CF 3 , OCF 3 , or t-butyl. 
     
     
         9 . A method as in  claim 1 , wherein R 3  is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF 3 , OCF 3 , F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl. 
     
     
         10 . A method as in  claim 1 , wherein R 3  is H, F, Cl, methyl, CF 3 , OCF 3 , or t-butyl. 
     
     
         11 . A method as in  claim 1 , wherein R 4  is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, R, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH 2 OMe. 
     
     
         12 . A method as in  claim 1 , wherein R 4  is H, methyl, F, or Cl. 
     
     
         13 . A method as in  claim 1 , wherein one or two of R 1-4  are not H. 
     
     
         14 . A method as in  claim 1 , wherein R 5  is H, F, Cl, methyl, or ethyl. 
     
     
         15 . A method as in  claim 1 , wherein R 5  is F, Cl, or methyl. 
     
     
         16 . A method as in  claim 1 , wherein R 6  is H, F, Cl, or methyl. 
     
     
         17 . A method as in  claim 1 , wherein R 7  is H, F, Cl, or methyl. 
     
     
         18 . A method as in  claim 1 , wherein R 8  is H, methyl, or OH. 
     
     
         19 . A method as in  claim 1 , wherein R 8  is H. 
     
     
         20 . A method as in  claim 1 , wherein R 9  and R 10  are, independently, selected from the group consisting of: H, methyl, ethyl, propyl, and isopropyl. 
     
     
         21 . A method as in  claim 1 , wherein each of R 9  and R 10  is, independently, H or methyl. 
     
     
         22 . A method as in  claim 1 , wherein R 11  is H, methyl, or ethyl. 
     
     
         23 . A method as in  claim 1 , wherein R 11  is methyl. 
     
     
         24 . A method for modulating an H 4  receptor, comprising exposing an H 4  receptor to at least one compound selected from: 
       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. 
     
     
         25 . A method for inhibiting leukocyte recruitment in a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of at least one chemical entity selected from compounds of formula (II), enantiomers, diastereomers, and racemates thereof, pharmaceutically acceptable salts, amides and esters thereof, 
       
         
           
           
               
               
           
         
       
       wherein
 X is N; 
 Y is O, NR 12  or CR 12 R 13 ; 
 Z is CR 14 ; 
 n is 1; 
 each of R 1-4  is, independently from other substituent assignments, H, C 1-4 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, C 3-6 cycloalkyl, —C 1-4 alkoxy, —C 1-4 alkylamino, —C 1-4 alkylthio, —C 1-4 alkylsulfonyl, —OC 3-6 cycloalkyl, —OCH 2 Ph, cyano, —CF 3 , F, Cl, Br, I, nitro, —OCF 3 , —SCF 3 , —OR c , —SR c , —S(O)R c , —SO 2 R c , —C(O)R c , phenyl, benzyl, phenethyl, —C(O)NR a R b , —C(O)OR c , —NR a R b , —CH 2 NR a R b  or —CH 2 OR c ; wherein each of R a , R b  and R c  is, independently from other substituent assignments, selected from H, C 1-4 alkyl, C 3-6 cycloalkyl, phenyl, (C 3-6 cycloalkyl)C 1-2 alkyl-, benzyl and phenethyl, or R a  and R b  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 >NC 1-6 alkyl, and wherein any phenyl, phenethyl, benzyl, alkyl or cycloalkyl moiety in any of said R 1-4 , R a , R b , R c , and said ring HetCyc1 is optionally, and independently from other substituent assignments, substituted with 1, 2 or 3 substituents selected from C 1-3 alkyl, halo, hydroxy, amino, and C 1-3 alkoxy; 
 each of R 5-7  is, independently from other substituent assignments, H, C 1-6 alkyl, F, Cl, Br, I, CF 3 , —OCF 3 , —OR c , —SR c , —S(O)R c , —SO 2 R c , C 1-4 alkoxy, cyano, nitro, —C(O)NR a R b , —C(O)phenyl, —C(O)C 1-6 alkyl, —S(O)C 1-4 alkyl, or —SO 2 C 1-4 alkyl; or, R 7  and R 6  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 C 1-3 alkyl, halo, hydroxy, amino, and C 1-3 alkoxy; 
 R 8  is H, C 1-6 alkyl, C 1-4 alkoxy, or OH; 
 each of R 9  and R 10  is, independently from other substituent assignments, H or C 1-6 alkyl, or R 9  and R 10  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 C 1-3 alkyl, halo, hydroxy, amino, and C 1-3 alkoxy; 
 R 11  is H, C 1-4 alkyl; 
 each of R 12  and R 13  is, independently from other substituent assignments, H or C 1-4 alkyl; or, when Y is CR 12 R 13 , R 12  and R 13  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 CR 12 R 13  is C═O; 
 R 14  is H, C 1-4 alkyl, OH, or C 1-4 alkoxy; 
 
       provided that:
 when Y is O or NR 12 , then R 8  is not OH or C 1-4 alkoxy; and 
 neither R 1  nor R 4  is C(O)NH 2 . 
 
     
     
         26 . A method as in  claim 25 , wherein Y is CR 12 R 13 . 
     
     
         27 . A method as in  claim 25 , wherein Y is CH 2 . 
     
     
         28 . A method as in  claim 25 , wherein Z is CH. 
     
     
         29 . A method as in  claim 25 , wherein R 1  is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH 2 OMe. 
     
     
         30 . A method as in  claim 25 , wherein R 1  is H, methyl, F, or Cl. 
     
     
         31 . A method as in  claim 25 , wherein R 2  is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF 3 , OCF 3 , F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl. 
     
     
         32 . A method as in  claim 25 , wherein R 2  is H, F, Cl, methyl, CF 3 , OCF 3 , or t-butyl. 
     
     
         33 . A method as in  claim 25 , wherein R 3  is selected from the group consisting of H, methyl, ethyl, isopropyl, t-butyl, cyclopropyl, CF 3 , OCF 3 , F, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and benzoyl. 
     
     
         34 . A method as in  claim 25 , wherein R 3  is H, F, Cl, methyl, CF 3 , OCF 3 , or t-butyl. 
     
     
         35 . A method as in  claim 25 , wherein R 4  is selected from the group consisting of H, methyl, ethyl, isopropyl, cyclopropyl, R, Cl, Br, cyano, phenyl, carboxymethyl, dimethylcarboxamido, and CH 2 OMe. 
     
     
         36 . A method as in  claim 25 , wherein R 4  is H, methyl, F, or Cl. 
     
     
         37 . A method as in  claim 25 , wherein one or two of R 1-4  are not H. 
     
     
         38 . A method as in  claim 25 , wherein R 5  is H, F, Cl, methyl, or ethyl. 
     
     
         39 . A method as in  claim 25 , wherein R 5  is F, Cl, or methyl. 
     
     
         40 . A method as in  claim 25 , wherein R 6  is H, F, Cl, or methyl. 
     
     
         41 . A method as in  claim 25 , wherein R 7  is H, F, Cl, or methyl. 
     
     
         42 . A method as in  claim 25 , wherein R 8  is H, methyl, or OH. 
     
     
         43 . A method as in  claim 25 , wherein R 8  is H. 
     
     
         44 . A method as in  claim 25 , wherein R 9  and R 10  are, independently, selected from the group consisting of: H, methyl, ethyl, propyl, and isopropyl. 
     
     
         45 . A method as in  claim 25 , wherein each of R 9  and R 10  is, independently, H or methyl. 
     
     
         46 . A method as in  claim 25 , wherein R 11  is H, methyl, or ethyl. 
     
     
         47 . A method as in  claim 25 , wherein R 11  is methyl. 
     
     
         48 . A method for inhibiting leukocyte recruitment in a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of at least one compound selected from: 
       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.

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