Substituted naphthyridine and quinoline compounds as MAO inhibitors
The invention provides a chemical entity of Formula (I) wherein R 1 , R 2 , R 3 , Y, and n have any of the values described herein and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting MAO, and MAO-B selectively, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders (including obesity, diabetes, and cardiometabolic disorders) and their associated co-morbidities.
1. A chemical entity, wherein the chemical entity is selected from the group consisting of compounds of Formula (I) and pharmaceutically acceptable salts of compounds of Formula (I)
wherein:
n is 1 or 2;
Y is CH or N;
R 1 is a pyridine substituted with —CF 3 , or phenyl substituted only in the meta and para positions with a total of one, two, or three R a members;
each R a is independently selected from the group consisting of halo, —C 1-4 alkyl, —CF 3 , —NO 2 , and —OC 1-4 alkyl;
R 2 is selected from the group consisting of —C(R b ) 2 R c or —CO—R d ;
each R b is independently selected from the group consisting of —H, —F, and —C 1-3 alkyl, or optionally two R b members are taken together with the carbon to which they are attached to form a C 3-6 cycloalkyl ring;
R c is selected from the group consisting of —F, —NH 2 , —OH, —OC 1-3 alkyl, —CH 2 OH, —CN, —CO 2 —C 1-4 alkyl, —CO—NHR e , and —C(CH 3 ) 2 OH; provided that when at least one R b is —F then R c is not —F;
R d is selected from the group consisting of —CH 3 , —OC 1-4 alkyl, —NHR e , and —NHCH 2 CH 2 N(R e ) 2 ;
each R e is independently —H or —CH 3 ; and
R 3 is selected from the group consisting of —H, —CH 3 , —OH, and —CF 3 .
2. A chemical entity as in claim 1 , wherein n is 1.
3. A chemical entity as in claim 1 , wherein n is 2.
4. A chemical entity as in claim 1 , wherein Y is CH.
5. A chemical entity as in claim 1 , wherein Y is N.
6. A chemical entity as in claim 1 , wherein R 1 is 2-(trifluoromethyl)pyridin-4-yl or 6-(trifluoromethyl)pyridin-2-yl.
7. A chemical entity as in claim 1 , wherein R 1 is phenyl substituted only in the meta and para positions with a total of, two, or three R a members independently selected from the group consisting of halo, —CF 3 , —CH 3 , —OCH 3 , and —NO 2 .
8. A chemical entity as in claim 1 , wherein R 1 is selected from the group consisting of 3-chlorophenyl, 3-fluorophenyl, 3-nitrophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-(trifluoromethyl)phenyl, 3-chloro-4-fluorophenyl, 3,4-difluorophenyl, 3-chloro-5-fluorophenyl, 3,5-difluorophenyl, 3-fluoro-5-(trifluoromethyl)phenyl, 3,4,5-trifluorophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-trifluoromethyl)phenyl, 4-fluoro-3-(trifluoromethyl)phenyl, 4-nitrophenyl, 4-methoxyphenyl, 2-(trifluoromethyl)pyridin-4-yl, and 6-(trifluoromethyl)pyridin-2-yl.
9. A chemical entity as in claim 1 , wherein R 2 is —(CR b ) 2 R c .
10. A chemical entity as in claim 1 , wherein R b is independently selected from the group consisting of —H, —F and —CH 3 .
11. A chemical entity as in claim 1 , wherein two R b members are taken together with the carbon to which they are attached to form a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl ring.
12. A chemical entity as in claim 1 , wherein R c is selected from the group consisting of —F, —NH 2 , —OH, —OCH 3 , —CH 2 OH, —CN, —CO 2 —C 1-4 alkyl, —CO—NHR e , and —C(CH 3 ) 2 OH.
13. A chemical entity as in claim 1 , wherein R 2 is selected from the group consisting of —CH 2 NH 2 , —CH 2 OH, —CH 2 CH 2 OH, —CH 2 OCH 3 , —CH 2 CN, —CH 2 (C═O)OCH 3 , —CH 2 (C═O)OCH 2 CH 3 , —CH 2 (C═O)NH 2 , —CH 2 (CH 3 ) 2 OH, —CH(OH)CH 3 , —C(CH 3 ) 2 OH, —C(CH 3 ) 2 CH 2 OH, —C(CH 3 ) 2 (C═O)NH 2 , —OCH 2 CH 3 , and —CF(CH 3 ) 2 .
14. A chemical entity as in claim 1 , wherein R 2 is —CO—R d .
15. A chemical entity as in claim 1 , wherein R d is selected from the group consisting of —CH 3 , —OC 1-4 alkyl, —NH 2 , —NH(CH 3 ), —NHCH 2 CH 2 NH(CH 3 ) and —NHCH 2 CH 2 N(CH 3 ) 2 .
16. A chemical entity as in claim 1 , wherein R 2 is selected from the group consisting of —(C═O)CH 3 , —C(═O)OCH 3 , —C(═O)OCH 2 CH 3 , —(C═O)NH 2 , —(C═O)NHCH 3 , —(C═O)N(CH 3 ) 2 , —C═O)NHCH 2 CH 2 NH 2 , —(C═O)NHCH 2 CH 2 NHCH 3 , and —(C═O)NHCH 2 CH 2 N(CH 3 ) 2 .
17. A chemical entity as in claim 1 , wherein R 3 is H or —CH 3 .
18. A chemical entity as in claim 1 , wherein R 3 is —CF 3 or —OH.
19. A chemical entity selected from the group consisting of:
Ethyl 7-[(4-chlorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-[(4-fluorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-[(3-chlorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-[(3-fluorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-((3-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-methylbenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-methylbenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-methoxybenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-methoxybenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-nitrobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-fluoro-3-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3,4-difluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3,5-difluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3,4,5-trifluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-chloro-4-fluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-nitrobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-chloro-5-fluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-chlorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-((3-fluorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-((4-fluorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-((3-chloro-4-fluorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-(3-fluorophenethoxyl)quinoline-3-carboxylate;
Ethyl 7-(3-chlorophenethoxyl)quinoline-3-carboxylate;
Methyl 7-((3-chlorobenzyl)oxy)quinoline-3-carboxylate;
2-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)propan-2-ol;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)propan-2-ol;
2-(7-((3,5-Difluorobenzyl)oxy)quinolin-3-yl)propan-2-ol;
2-(7((3,4,5-Trifluorobenzyl)oxy)quinolin-3-yl)propan-2-ol;
2-(7-((4-Fluorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
2-(7-((3-Chlorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
2-(7-((3-Chloro-4-fluorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
2-(7-((3-Fluorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)methanol;
(7-((3,5-Difluorobenzyl)oxy)quinolin-3-yl)methanol;
(7-((3,4,5-Trifluorobenzyl)oxy)quinolin-3-yl)methanol;
2-(7-(3-Fluorophenethoxyl)quinolin-3-yl)propan-2-ol;
2-(7-(3-Chlorophenethoxyl)quinolin-3-yl)propan-2-ol;
7-((3-Chlorobenzyl)oxy)-3-(methoxymethyl)quinoline;
7-((4-Fluorobenzyl)oxy)-3-(2-fluoropropan-2-yl)quinoline;
1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanone;
1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanol;
(R)-1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanol;
(S)-1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanol;
7-((3-Chlorobenzyl)oxy)-N-methylquinoline-3-carboxamide;
N-(2-Aminoethyl)-7-((3-chlorobenzyl)oxy)quinoline-3-carboxamide;
7-((3-Chlorobenzyl)oxy)-N-(2-(methylamino)ethyl)quinoline-3-carboxamide;
7-((3-Chlorobenzyl)oxy)-N-(2-(dimethylamino)ethyl)quinoline-3-carboxamide;
(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)methanamine;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)acetamide;
Ethyl 2-(7-((3-fluorobenzyl)oxy)quinolin-3-yl)acetate;
Ethyl 2-(7((4-fluorobenzyl)oxy)quinolin-3-yl)acetate;
Methyl 2-(7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)acetamide;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)ethanol;
2-(7-((3-Fluorobenzyl)oxy)quinolin-3-yl)acetamide;
2-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)acetamide;
Ethyl 2-(7((3-chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropanoate;
2-(7((3-Chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropan-1-ol;
2-(7((3-Chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropanamide;
2-(7-((2-(Trifluoromethyl)pyridin-4-yl)methoxy)quinolin-3-yl)acetamide;
1-(7((3-Chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropan-2-ol;
7-((3-Chlorobenzyl)oxy)quinoline-3-carboxamide;
2-{7-[(4-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
7-[(4-Fluorophenyl)methoxy]-3-(2-hydroxypropan-2-yl)quinolin-1-ium-1-olate;
7-[(3-Fluorophenyl)methoxy]-1,5-naphthyridine-3-carboxamide;
7-((4-Fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxamide;
7-((3-Chlorobenzyl)oxy)-1,5-naphthyridine-3-carboxamide;
7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridine-3-carboxamide;
7-[(3-Chloro-4-fluorophenyl)methoxy]-1,5-naphthyridine-3-carboxamide;
7-[(3-Chlorophenyl)methoxy]-N-methyl-1,5-naphthyridine-3-carboxamide;
(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanol;
2-{7-[(3,4-Difluorophenyl)methoxy]-1,5-naphthyridin-3-yl}acetonitrile;
3-[(4-Fluorophenyl)methoxy]-7-(2-fluoropropan-2-yl)-1,5-naphthyridine;
2-{7-[(3-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-{7-[(3,4-Difluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-{7-[(3-Chloro-4-fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-{7-[(3-Chlorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetamide;
2-(7-((6-(Trifluoromethyl)pyridin-2-yl)methoxy)-1,5-naphthyridin-3-yl)acetamide;
2-(7-((3-Chlorobenzyl)oxy)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)acetamide;
2-(7-((3-Chlorobenzyl)oxy)-2-oxo-1,2-dihydroquinolin-3-yl)acetamide; and pharmaceutically acceptable salts thereof.
20. A pharmaceutical composition comprising an effective amount of at least one chemical entity selected from the compounds of Formula (I),
wherein:
n is 1 or 2;
Y is CH or N;
R 1 is a pyridine substituted with —CF 3 , or phenyl substituted only in the meta and para positions with a total of one, two, or three R a members;
each R a is independently selected from the group consisting of halo, —C 1-4 alkyl, CF 3 , —NO 2 , and —OC 1-4 alkyl;
R 2 is selected from the group consisting of —C(R b ) 2 R c or —CO—R d ;
each R b is independently selected from the group consisting of —H, —F, and —C 1-3 alkyl, or optionally two R b members are taken together with the carbon to which they are attached to form a C 3-6 cycloalkyl ring;
R c is selected from the group consisting of —F, —NH 2 , —OH, —OC 1-3 alkyl, —CH 2 OH, —CN, —CO 2 —C 1-4 alkyl, —CO—NHR e , and —C(CH 3 ) 2 OH; provided that when at least one R b is —F then R c is not —F;
R d is selected from the group consisting of —CH 3 , —OC 1-4 alkyl, —NHR e , and —NHCH 2 CH 2 N(R e ) 2 ;
each R e is independently —H or —CH 3 ;
R 3 is selected from the group consisting of —H, —CH 3 , —OH, and —CF 3 ,
and pharmaceutically acceptable salts of compounds of Formula (I).
21. A pharmaceutical composition comprising an effective amount of at least one chemical entity of claim 1 .
22. A pharmaceutical composition comprising an effective amount of at least one chemical entity of claim 19 .
23. A method for modulating one or more monoamine oxidase (MAO) enzymes, comprising exposing MAO-A or MAO-B to an effective amount of at least one chemical entity selected from compounds of Formula (I)
wherein:
n is 1 or 2;
Y is CH or N;
R 1 is a pyridine substituted with —CF 3 , or phenyl substituted only in the meta and para positions with a total of one, two, or three R a members;
each R a is independently selected from the group consisting of halo, —C 1-4 alkyl, CF 3 , —NO 2 , and —OC 1-4 alkyl;
R 2 is selected from the group consisting of —C(R b ) 2 R c or —CO—R d ;
each R b is independently selected from the group consisting of —H, —F, and —C 1-3 alkyl, or optionally two R b members are taken together with the carbon to which they are attached to form a C 3-6 cycloalkyl ring;
R c is selected from the group consisting of —F, —NH 2 , —OH, —OC 1-3 alkyl, —CH 2 OH, —CN, —CO 2 —C 1-4 alkyl, —CO—NHR e , and —C(CH 3 ) 2 OH; provided that when at least one R b is —F then R c is not —F;
R d is selected from the group consisting of —CH 3 , —OC 1-4 alkyl, —NHR e , and —NHCH 2 CH 2 N(R e ) 2 ;
each R e is independently —H or —CH 3 ;
R 3 is selected from the group consisting of —H, —CH 3 , —OH, and —CF 3 ,
and pharmaceutically acceptable salt of compounds of Formula (I).
24. A method for modulating one or more monoamine oxidase (MAO) enzymes, comprising exposing MAO-A or MAO-B to an effective amount of at least one chemical entity of claim 19 .
25. The method of claim 24 , wherein said one or more MAO enzymes is in a human subject.
26. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
Ethyl 7-[(4-chlorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-[(4-fluorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-[(3-chlorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-[(3-fluorophenyl)methoxy]quinoline-3-carboxylate;
Ethyl 7-((3-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-methylbenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-methylbenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-methoxybenzyl)oxy)quinoline-3-carboxylate; and
Ethyl 7-((4-methoxybenzyl)oxy)quinoline-3-carboxylate.
27. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
Ethyl 7-((4-nitrobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((4-fluoro-3-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3,4-difluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3,5-difluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3,4,5-trifluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-chloro-4-fluorobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-nitrobenzyl)oxy)quinoline-3-carboxylate;
Ethyl 7-((3-chloro-5-fluorobenzyl)oxy)quinoline-3-carboxylate; and
Ethyl 7-((3-chlorobenzyl)oxy)-2-methylquinoline-3-carboxylate.
28. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
Ethyl 7-((3-fluorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-((4-fluorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-((3-chloro-4-fluorobenzyl)oxy)-2-methylquinoline-3-carboxylate;
Ethyl 7-(3-fluorophenethoxyl)quinoline-3-carboxylate;
Ethyl 7-(3-chlorophenethoxyl)quinoline-3-carboxylate;
Methyl 7-((3-chlorobenzyl)oxy)quinoline-3-carboxylate;
2-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)propan-2-ol;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)propan-2-ol;
2-(7-((3,5-Difluorobenzyl)oxy)quinolin-3-yl)propan-2-ol; and
2-(7((3,4,5-Trifluorobenzyl)oxy)quinolin-3-yl)propan-2-ol.
29. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
2-(7-((4-Fluorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
2-(7-((3-Chlorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
2-(7-((3-Chloro-4-fluorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
2-(7-((3-Fluorobenzyl)oxy)-2-methylquinolin-3-yl)propan-2-ol;
(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)methanol;
(7-((3,5-Difluorobenzyl)oxy)quinolin-3-yl)methanol;
(7-((3,4,5-Trifluorobenzyl)oxy)quinolin-3-yl)methanol;
2-(7-(3-Fluorophenethoxy)quinolin-3-yl)propan-2-ol;
2-(7-(3-Chlorophenethoxy)quinolin-3-yl)propan-2-ol; and
7-((3-Chlorobenzyl)oxy)-3-(methoxymethyl)quinoline.
30. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
7-((4-Fluorobenzyl)oxy)-3-(2-fluoropropan-2-yl)quinoline;
1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanone;
1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanol;
(R)-1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanol;
(S)-1-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)ethanol;
7-((3-Chlorobenzyl)oxy)-N-methylquinoline-3-carboxamide;
N-(2-Aminoethyl)-7-((3-chlorobenzyl)oxy)quinoline-3-carboxamide;
7-((3-Chlorobenzyl)oxy)-N-(2-(methylamino)ethyl)quinoline-3-carboxamide;
7-((3-Chlorobenzyl)oxy)-N-(2-(dimethylamino)ethyl)quinoline-3-carboxamide; and
(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)methanamine.
31. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)acetamide;
Ethyl 2-(7-((3-fluorobenzyl)oxy)quinolin-3-yl)acetate;
Ethyl 2-(7-((4-fluorobenzyl)oxy)quinolin-3-yl)acetate;
Methyl 2-(7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)acetamide;
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)ethanol;
2-(7-((3-Fluorobenzyl)oxy)quinolin-3-yl)acetamide;
2-(7-((4-Fluorobenzyl)oxy)quinolin-3-yl)acetamide;
Ethyl 2-(7-((3-chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropanoate; and
2-(7((3-Chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropan-1-ol.
32. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
2-(7-((3-Chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropanamide;
2-(7-((2-(Trifluoromethyl)pyridin-4-yl)methoxy)quinolin-3-yl)acetamide;
1-(7((3-Chlorobenzyl)oxy)quinolin-3-yl)-2-methylpropan-2-ol;
7-((3-Chlorobenzyl)oxy)quinoline-3-carboxamide;
2-{7-[(4-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
7-[(4-Fluorophenyl)methoxy]-3-(2-hydroxypropan-2-yl)quinolin-1-ium-1-olate;
7-[(3-Fluorophenyl)methoxy]-1,5-naphthyridine-3-carboxamide;
7-((4-Fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxamide;
7-((3-Chlorobenzyl)oxy)-1,5-naphthyridine-3-carboxamide;
7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridine-3-carboxamide;
7-[(3-Chloro-4-fluorophenyl)methoxy]-1,5-naphthyridine-3-carboxamide; and
7-[(3-Chlorophenyl)methoxy]-N-methyl-1,5-naphthyridine-3-carboxamide.
33. A chemical entity as in claim 19 , wherein the chemical entity is selected from the group consisting of:
(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanol;
2-{7-[(3,4-Difluorophenyl)methoxy]-1,5-naphthyridin-3-yl}acetonitrile;
3-[(4-Fluorophenyl)methoxy]-7-(2-fluoropropan-2-yl)-1,5-naphthyridine;
2-{7-[(3-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-{7-[(3,4-Difluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-{7-[(3-Chloro-4-fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-{7-[(3-Chlorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol;
2-(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetamide;
2-(7-((6-(Trifluoromethyl)pyridin-2-yl)methoxy)-1,5-naphthyridin-3-yl)acetamide;
2-(7-((3-Chlorobenzyl)oxy)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)acetamide; and
2-(7-((3-Chlorobenzyl)oxy)-2-oxo-1,2-dihydroquinolin-3-yl)acetamide.
34. A chemical entity as in claim 1 , wherein the chemical entity is a compound of Formula (I).
35. A chemical entity as in claim 1 , wherein the chemical entity is a pharmaceutically acceptable salt of a compound of Formula (I).