Substituted benzimidazole derivatives as D-amino acid oxidase (DAAO) inhibitors

1. A method of inhibiting a DAAO, comprising contacting a cell with a compound of formula (I),

wherein n is 0 or 1,

X is —S—, —S(═O)— or —NR n —; wherein

Rn is H or

A is —CH, —CR c or N;

R a is —C(═O)OR a1 , —OR a2 , —O—C(═O)R a3 or —O—C(═O)-T-OR a4 ; wherein

R a1 is H or linear or branched C 1-15 alkyl;

R a2 is H, linear or branched C 1-15 alkyl, phosphonate, diarylphosphonate or an O-protecting group;

R a3 and R a4 are independently a protecting group, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, -T-C 3-10 cycloalkyl, -T-NHR a3p , -T-C 3-10 cycloalkenyl, -T-C 6-10 aryl, -T-C 5-10 heteroaryl, -T-NH—C(═O)—O—C 1-10 alkyl, -T-adamantyl or —C 1-3 alkylene-C 6-10 aryl where the alkylene is substituted with -T-NHR a3p ;

R a3p is H or an N-protecting group;

R b is H, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

R c each is independently linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxyl, unprotected or protected hydroxyl group, or —C 1-10 alkylene-Y—C 6-10 heteroaryl wherein —Y— is —CH 2 —, —NH—, —O— or —S—;

symbol * represents the bonding position;

m is an integer from 0 to 4;

-T- is absent, C 1-3 alkylene or C 2-3 alkenylene;

-T′- is C 1-3 alkylene or C 2-3 alkenylene; and

wherein the heteroaryl contains at least one heteroatom, each heteroatom being independently S, N or O;

wherein the alkyl, alkenyl, alkoxy, cycloalkyl, aryl, heteroaryl, alkylene and alkenylene are each independently unsubstituted or substituted with at least one substituent;

wherein the substituent is each independently a halogen, a protecting group, protected or unprotected amino group, nitro, nitroso, linear or branched C 1-15 alkyl, or linear or branched C 1-15 alkoxy or C 3-10 cycloalkyl; and

when R b is H, the tautomers are included,

with the proviso that

when X is —S— or —S(═O)—, R a is —OR a2 and R a2 is H or linear or branched C 1-15 alkyl, then A is —CH or —CR c ;

when X is —S— or —S(═O)— and R a is —C(═O)OR a 1, R b is linear or branched C 6-15 alkyl, linear or branched C 6-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

or a pharmaceutically acceptable salt thereof.

2. A method of treating a disease associated with DAAO inhibition in a subject, which comprises administrating to said subject an effective amount of a compound of formula (I),

wherein n is 0 or 1,

X is —S—, —S(═O)— or —NR n —; wherein

R n is H or

A is —CH, —CR c or N;

R a is —C(═O)OR a1 —OR a2 , —O—C(═O)R a3 or —O—C(═O)-T-OR a4 ; wherein

R a1 is H or linear or branched C 1-15 alkyl;

R a2 is H, linear or branched C 1-15 alkyl, phosphonate, diarylphosphonate or an O-protecting group;

R a3 and R a4 are independently a protecting group, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, -T-C 3-10 cycloalkyl, -T-NHR a3p , -T-C 3-10 cycloalkenyl, -T-C 6-10 aryl, -T-C 5-10 heteroaryl, -T-NH—C(═O)—O—C 1-10 alkyl, -T-adamantyl or —C 1-3 alkylene-C 6-10 aryl where the alkylene is substituted with -T-NHR a3p ;

R a3p is H or an N-protecting group;

R b is H, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

R c each is independently linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxyl, unprotected or protected hydroxyl group, or —C 1-10 alkylene-Y—C 6-10 heteroaryl wherein —Y— is —CH 2 —, —NH—, —O— or —S—;

symbol * represents the bonding position;

m is an integer from 0 to 4;

-T- is absent, C 1-3 alkylene or C 2-3 alkenylene;

-T′- is C 1-3 alkylene or C 2-3 alkenylene; and

wherein the heteroaryl contains at least one heteroatom, each heteroatom being independently S, N or O;

wherein the alkyl, alkenyl, alkoxy, cycloalkyl, aryl, heteroaryl, alkylene and alkenylene are each independently unsubstituted or substituted with at least one substituent;

wherein the substituent is each independently a halogen, a protecting group, protected or unprotected amino group, nitro, nitroso, linear or branched C 1-15 alkyl, or linear or branched C 1-15 alkoxy or C 3-10 cycloalkyl; and

when R b is H, the tautomers are included,

with the proviso that

when X is —S— or —S(═O)—, R a is —OR a2 and R a2 is H or linear or branched C 1-15 alkyl, then A is —CH or —CR c ;

when X is —S— or —S(═O)— and R a is —C(═O)OR a1 , R b is linear or branched C 6-15 alkyl, linear or branched C 6-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

or a pharmaceutically acceptable salt thereof.

3. The method of claim 2 , wherein the disease is symptom domains of schizophrenia and schizoaffective disorder, depression, Tourette Syndrome, Post-traumatic stress disorder (PTSD), Obsessive-compulsive disorder (OCD), analgesics, loss of memory and/or cognition associated with neurodegenerative diseases or loss of neuronal function characteristic of neurodegenerative diseases.

4. The method of claim 3 , wherein the symptom domains of schizophrenia and schizoaffective disorder include negative, cognitive, depressive, positive and general psychopathology symptom domains.

5. The method of claim 2 , wherein the disease is mild cognitive impairment (MCI), Alzheimer's disease, Parkinson's disease or schizophrenia.

6. The method of claim 2 , wherein the disease associated with DAAO inhibition is pain, ataxia or convulsion.

7. The method of any of claim 1 or 2 , wherein the compound is a compound of formula (I-a):

wherein n is 0 or 1,

X is —S—, —S(═O)— or —NR n —; wherein

Rn is H or

A is —CH, —CR c or N;

R a is —C(═O)OR a1 , —OR a2 , —O—C(═O)R a3 or —O—C(═O)-T-OR a4 ; wherein

R a1 is H or linear or branched C 1-15 alkyl;

R a2 is H, linear or branched C 1-15 alkyl, diarylphosphonate or an O-protecting group;

R a3 and R a4 are independently a protecting group, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, -T-C 3-10 cycloalkyl, -T-NHR a3p , -T-C 3-10 cycloalkenyl, -T-C 6-10 aryl, -T-C 5 -10heteroaryl, -T-NH—C(═O)—O—C 1-10 alkyl or -T-adamantyl;

R a3p is H or an N-protecting group;

R b is H, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

R C each is independently linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxyl, unprotected or protected hydroxyl group, or —C 1-10 alkylene-Y—C 6-10 heteroaryl wherein —Y— is —CH 2 —, —NH—, —O— or —S—;

symbol * represents the bonding position;

m is an integer from 0 to 4;

-T- is absent, C 1-3 alkylene or C 2-3 alkenylene;

-T′- is C 1-3 alkylene or C 2-3 alkenylene; and

wherein the heteroaryl contains at least one heteroatom, each heteroatom being independently S, N or O;

wherein the alkyl, alkenyl, alkoxy, cycloalkyl, aryl, heteroaryl, alkylene and alkenylene are each independently unsubstituted or substituted with at least one substituent;

wherein the substituent is each independently a halogen, a protecting group, protected or unprotected amino group, nitro, nitroso, linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxy or C 3-10 cycloalkyl and

when R b is H, the tautomers are included,

with the proviso that

when X is —S— or —S(═O)—, R a is —OR a2 and R a2 is H or linear or branched C 1-15 alkyl, then A is —CH or —CR c ;

when X is —S— or —S(═O)— and R a is —C(═O)OR a 1, R b is linear or branched C 6-15 alkyl, linear or branched C 6-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

or a pharmaceutically acceptable salt thereof.

8. The method of claim 7 ,

wherein n is 0 or 1;

X is —S—, —S(═O)— or —NR n —;

R n is H or

A is —CH, —CR c or N;

R a is —OR a2 , —O—C(═O)R a3 or —O—C(═O)-T-OR a4 ;

R a2 is H, linear or branched C 1-15 alkyl, phosphonate, diarylphosphonate or an O-protecting group;

R a3 and R a4 are independently a protecting group, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, -T-C 3-10 cycloalkyl, -T-NHR a3p , -T-C 3-10 cycloalkenyl, -T-C 6-10 aryl, -T-C 5-10 heteroaryl, -T-NH—C(═O)—O—C 1-10 alkyl, -T-adamantyl or —C 1-3 alkylene-C 6-10 aryl where the alkylene is substituted with -T-NHR a3p ;

R a3p is H or an N-protecting group;

R b is H, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

R c each is independently linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxyl, unprotected or protected hydroxyl group, or —C 1-10 alkylene —Y—C 6-10 heteroaryl wherein —Y— is —CH 2 —, —NH—, —O— or —S—;

symbol * represents the bonding position;

m is an integer from 0 to 4;

-T- is absent, C 1-3 alkylene or C 2-3 alkenylene;

-T′- is C 1-3 alkylene or C 2-3 alkenylene; and

wherein the heteroaryl contains at least one heteroatom, each heteroatom being independently S, N or O;

wherein the alkyl, alkenyl, alkoxy, cycloalkyl, aryl, heteroaryl, alkylene and alkenylene are each independently unsubstituted or substituted with at least one substituent;

wherein the substituent is each independently a halogen, a protecting group, protected or unprotected amino group, nitro, nitroso, linear or branched C 1-15 alkyl, or linear or branched C 1-15 alkoxy or C 3-10 cycloalkyl; and

when R b is H, the tautomers are included,

with the proviso that

when X is —S— or —S(═O)—, R a is —OR a2 and R a2 is H or linear or branched C 1-15 alkyl, then

A is —CH or —CR c ;

or a pharmaceutically acceptable salt.

9. The method of claim 7 , wherein:

n is 0;

X is —S(═O)—;

A is N;

R a is —OR a2 , —O—C(═O)R a3 or —O—C(═O)-T-OR a4 , wherein R a2 is H, linear or branched

C 1-15 alkyl, phosphonate, diarylphosphonate or an O-protecting group;

R a3 and R a4 are each independently a protecting group, linear or branched C 1-15 alkyl, linear or branched C 2-15 alkenyl, -T-C 3-10 cycloalkyl, -T-NHR a3p , -T-C 3-10 cycloalkenyl, -T-C 6-10 aryl, -T-C 5-10 heteroaryl, -T-NH—C(═O)—O—C 1-10 alkyl, -T-adamantyl or —C 1-3 alkylene-C 6-10 aryl where the alkylene is substituted with -T-NHR a3p ; R a3p is H or an N-protecting group;

R b is H;

m is 3; and

R c each is independently linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxyl;

or a pharmaceutically acceptable salt.

10. The method of claim 7 , wherein n is 0.

11. The method of claim 7 , wherein m is an integer from 0 to 3.

12. The method of claim 7 , wherein R a is —C(═O)OH, —C(═O)OC 1-4 alkyl, H, —OR a2 wherein R a2 is H, linear or branched C 1-10 alkyl or an O-protecting group; —O—C(═O)R a3 wherein R a3 is independently tert-butyl protecting group; linear or branched C 1-10 alkyl unsubstituted or substituted by halogen, tert-butyl protecting group or protected amino group; linear or branched C 2-10 alkenyl; C 1-4 alkoxy; C 3-10 cycloalkyl; —C 1-3 alkylene-C 3-10 cycloalkyl; —C 3-10 cycloalkenyl; —C 6-10 aryl unsubstituted or substituted by C 1-10 alkyl, nitro, C 1-15 alkoxy or halogen; —C 5-10 heteroaryl unsubstituted or substituted by C 1-10 alkoxy; C 2-3 alkenylene-C 6-10 aryl wherein C 6-10 aryl is unsubstituted or substituted by halogen; —C 1-3 alkylene-NH—C(═O)—O—C 1-10 alkyl; or adamantly; or —O—C(═O)—O—C 1-10 alkyl.

13. The method of claim 7 , wherein R a is —O—C 1-10 alkyl; —O—protecting group or —O—C(═O)R a3 wherein R a3 is a tert-butyl protecting group; adamantly; linear or branched C 1-10 alkyl unsubstituted or substituted by halogen or a tert-butyl protecting group; C 1-4 alkoxy; —C 6-10 aryl unsubstituted or substituted by C 1-10 alkyl, nitro, C 1-15 alkoxy or halogen; C 3-10 cycloalkyl; —C 3-10 cycloalkenyl; linear or branched C 2-10 alkenyl; —C 5-10 heteroaryl; —C 1-3 alkylene-C 3-10 cycloalkyl; C 2-3 alkenylene-C 6-10 aryl wherein C 6-10 aryl is unsubstituted or substituted by halogen; —O—C(═O)—O—C 1-10 alkyl.

14. The method of claim 7 , wherein R a is —O—C 1-4 alkyl, —O-tert-butyloxycarbonyl protecting group or —O—C(═O)R a3 wherein R a3 is a tert-butyl protecting group; adamantly; linear or branched C 1-8 alkyl unsubstituted or substituted by halogen or a tert-butyl protecting group; C 1-4 alkoxy; - phenyl unsubstituted or substituted by C 1-6 alkyl, nitro, C 1-4 alkoxy or halogen; C 3-6 cycloalkyl; - C 3-6 cycloalkenyl; linear or branched C 2-6 alkenyl; —C 5-6 heteroaryl; —C 1-3 alkylene-C 3-6 cycloalkyl; C 2-3 alkenylene-phenyl wherein phenyl is unsubstituted or substituted by halogen; —O—C(═O)—O—C 1-4 alkyl.

15. The method of claim 7 , wherein R a is —OH, —COOH, —O-phosphate, —O—C 1-6 alkyl or —O—C(═O)—C 1-6 alkyl, —O—C(═O)—C 1-4 alkylene-NH(Fmoc or Boc_protecting group), or —O—C(═O)—NH—C(═O)—O—C 1-10 alkyl.

16. The method of claim 7 , wherein Re each is independently halogen, linear or branched C 1-6 alkyl, linear or branched C 1-6 alkoxyl, or —C 1-10 alkenylene-Y—C 6-10 heteroaryl; wherein Y is S and C 6-10 heteroaryl is unsubstituted or substituted by C 1-15 alkyl (preferably C 1-4 alkyl), C 1-15 alkenyl (preferably C 2-4 alkyl), C 1-15 alkoxy (preferably C 1-4 alkoxy), —OH, —NH 2 , —NO 2 or halogen.

17. The method of claim 7 , wherein the compound is selected from the group consisting of:

21122: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl acetate)

21124: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl benzoate)

26096: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl butyrate)

26097: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl cyclohexanecarboxylate)

26098: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-butylbenzoate)

21127: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3-methylbenzoate)

27076: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl hexanoate

27077: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl isobutyrate

27078: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl cyclohex-3-ene-1-carboxylate)

27079: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl cyclohex-3-enecarboxylate

28087: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-methylbenzoate)

28091: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-nitrobenzoate)

28092: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl cyclopropanecarboxylate)

28093: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-ethylbutanoate)

28094: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-phenylacetate)

28095: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3,5,5-trimethylhexanoate

28096: (2-(((5-methoxy-4,6-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-ethoxybenzoate)

21123: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl propionate)

21125: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-chlorobenzoate)

21126: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3-nitrobenzoate)

21128: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl heptanoate

21129: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-fluorobenzoate)

21130: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl (Z)-2-methylbut-2-enoate)

21131: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-chloropropanoate)

21132: tert-butyl (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl) carbonate

12124: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl (Z)-but-2-enoate)

12125: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3-methylbut-2-enoate)

12122: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl furan-2-carboxylate)

12123: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl acrylate)

12127: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-methylbutanoate)

12128: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3-cyclopentylpropanoate)

12129: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl (E)-3-(2-chlorophenyl)acrylate)

12130: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 6-bromohexanoate)

11021: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-fluorobenzoate)

11020: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-methoxybenzoate)

11022: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl (3r,5r,7r)-adamantane-1-carboxylate)

11023: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl isoxazole-5-carboxylate)

11030: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-(tert-butyl)benzoate)

11031: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3-chloro-4-fluorobenzoate)

25015: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl pivalate)

25016: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl pentanoate)

25017: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 4-nitrobenzoate)

25027: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl cyclobutanecarboxylate)

25028: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl thiophene-2-carboxylate)

25029: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-methylbutanoate)

25030: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 3,3-dimethylbutanoate)

25031: (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl 2-methoxyacetate) and

25032: (ethyl (2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl) carbonate)

or a pharmaceutically acceptable salt thereof.

18. The method of claim 7 , wherein the compound is selected from the group consisting of:

12082: Methyl 1-(2-(cyclohex-1-en-1-yl)ethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzo[d]imidazole-5-carboxylate

12083: 1-(2-(cyclohex-1-en-1-yl)ethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzo[d]imidazole-5-carboxylic acid

12084: Methyl 1-(2-(cyclohex-1-en-1-yl)ethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole-5-carboxylate

12088: methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)-1-octyl-1H-benzo[d]imidazole-5-carboxylate

21098: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-propyl-1H-benzo[d]imidazole-5-carboxylate

26065: Methyl 1-(furan-2-ylmethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1H-benzo[d]imidazole-5-carboxylate

21102: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-propyl-1H-benzo[d]imidazole-5-carboxylic acid

21103: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-(3-methoxypropyl)-1H-benzo[d]imidazole-5-carboxylate

21104: 2-(bis((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1- (3-methoxypropyl)-1H-benzo[d]imidazole-5-carboxylic acid

26066: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-pentyl-1H-benzo[d]imidazole-5-carboxylate

21105: 2-(bis((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1- (2-(cyclohex-1-en-1-yl)ethyl)-1H-benzo[d]imidazole-5-carboxylic acid

26070: 1-(furan-2-ylmethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1H-benzo[d]imidazole-5-carboxylic acid

26071: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-(4-methoxybenzyl)-1H-benzo[d]imidazole-5-carboxylate

26072: Methyl 2-(bis((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3-(furan-2-ylmethyl)-3,4-dihydroquinazoline-7-carboxylate

21106: Methyl 3-(2-(cyclohex-1-en-1-yl)ethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3,4-dihydroquinazoline-7-carboxylate

12092: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzo[d]imidazol-5-yl (((9H-fluoren-9-yl)methoxy)carbonyl)glycinate

12093: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)-1H-benzo[d]imidazol-5-yl (tert-butoxycarbonyl)glycinate

21110: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3- (3-methoxypropyl)-3,4-dihydroquinazoline-7-carboxylic acid

26076: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-pentyl-1H-benzo[d]imidazole-5-carboxylic acid

26077: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-(4-methoxybenzyl)-1H-benzo[d]imidazole-5-carboxylic acid

12094: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)thio)-1H benzo[d]-imidazole-5-yl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-phenylacetate

13001: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-6-yl 2-((tert-butoxycarbonyl)amino)acetate

13084: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazol-5-yl diphenyl phosphate

26079: Methyl 3-(furan-2-ylmethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3,4-dihydroquinazoline-7-carboxylate

26089: 3-(furan-2-ylmethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3,4-dihydroquinazoline-7-carboxylic acid

26090: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3-pentyl-3,4-dihydroquinazoline-7-carboxylic acid

26091: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3-pentyl-3,4-dihydroquinazoline-7-carboxylate

26092: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-3-(4-methoxybenzyl)-3,4-dihydroquinazoline-7-carboxylate

21115: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1- (3-methoxypropyl)-1H-benzo[d]imidazole-5-carboxylic acid

21116: Methyl 1-(2-(cyclohex-1-en-1-yl)ethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1H-benzo[d]imidazole-5-carboxylate

21117: 1-(2-(cyclohex-1-en-1-yl)ethyl)-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1H-benzo[d]imidazole-5-carboxylic acid

21118: Methyl 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-phenethyl-1H-benzo[d]imidazole-5-carboxylate

21119: 2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-phenethyl-1H-benzo[d]imidazole-5-carboxylic acid

21120: 2-(bis((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-propyl-1H-benzo[d]imidazole-5-carboxylic acid

21121: 2-(bis((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amino)-1-phenethyl-1H-benzo[d]imidazole-5-carboxylic acid

22138: 5-methoxy-2-((2-methoxy-3,6-dimethylbenzyl)thio)-1H-benzo[d]imidazole

22139: 5-methoxy-2-((2-methoxy-3,6-dimethylbenzyl)sulfinyl)-1H-benzo[d]imidazole

22140: 2,2′-(((2-methoxy-4-methyl-1,3-phenylene)bis(methylene))bis(sulfanediyl))bis(5-methoxy-1H-benzo[d]imidazole)

21133: 2-((3-(bromomethyl)-2-((tert-butyldimethylsilyl)oxy)-6-methylbenzyl)thio)-5-methoxy-1H-benzo[d]imidazole and

22141: 2-((2-methoxy-3,6-dimethylbenzyl)thio)-1H-benzo[d]imidazol-5-ol or a pharmaceutically acceptable salt thereof.

19. The method of any of claim 1 or 2 , wherein the compound is a compound of formula (I-b):

wherein n is 0 or 1,

X is —S—, —S(═O)— or —NR n —;

Rn is H or

A is —CH, —CR c or N;

R a is —C(═O)OR a1 , —OR a2 or —O—C(═O)R a3 ; wherein

R a1 is H or linear or branched C 1-15 alkyl;

R a2 is H, linear or branched C 1-15 alkyl, phosphonate, diarylphosphonate or an O-protecting group;

R a3 is -T-NHR a3p , -T-NH—C(═O)—O—C 1-10 alkyl or —C 1-3 alkylene-C 6-10 aryl where the alkylene is substituted with -T-NHR a3p ;

R a3p is H or an N-protecting group;

R b is H, linear or branched C 1-15 alkyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

R c each is independently linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxyl, unprotected or protected hydroxyl group or —C 1-10 alkylene-Y-C 6-10 heteroaryl wherein —Y— is —CH 2 —, —NH—, —O— or —S—;

symbol * represents the bonding position;

m is an integer from 0 to 4;

-T- is absent, C 1-3 alkylene or C 2-3 alkenylene;

-T′- is C 1-3 alkylene; and

wherein the heteroaryl contains at least one heteroatom, each heteroatom being independently S, N or O;

wherein the alkyl, alkenyl, alkoxy, cycloalkyl, aryl and heteroaryl are each independently unsubstituted or substituted with at least one substituent;

wherein the substituent is each independently a halogen, protected or unprotected amino group, nitro, nitroso, linear or branched C 1-15 alkyl, linear or branched C 1-15 alkoxy or C 3-10 cycloalkyl; and

when R b is H, the tautomers are included,

with the proviso that

when X is —S— or —S(═O)—, R a is —OR a2 and R a2 is H or linear or branched C 1-15 alkyl, then A is —CH or —CR c ;

when X is —S— or —S(═O)— and R a is —C(═O)OR a1 , R b is linear or branched C 6-10 alkyl, linear or branched C 6-15 alkenyl, C 1-3 alkoxy-C 1-15 alkyl-, -T′-C 3-10 cycloalkyl, -T′-C 3-10 cycloalkenyl, -T′-C 6-10 aryl or -T′-C 5-10 heteroaryl;

or a pharmaceutically acceptable salt thereof.