Substituted piperidine compounds and their use as orexin receptor modulators
The present invention is directed to compounds of Formula I: wherein X is CR 1 or N; Y is CR 2 or N; Z is NH or O; R 1 is alkoxy, triazolyl, oxazolyl, isoxazolyl, oxadiazolyl, or pyrimidinyl; R 2 is H, alkyl, or halo; R 3 is H, alkyl, alkoxy, halo, triazolyl, oxazolyl, or pyrimidinyl; R 4 is alkyl; R 5 is pyridyl; benzoxazolyl; pyrimidinyl; pyridazinyl; quinoxalinyl; pyrazinyl; or quinazolinyl; wherein the pyridyl; benzoxazolyl; pyrimidinyl; pyridazinyl; quinoxalinyl; pyrazinyl; or quinazolinyl is optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl; and R 6 is H or alkyl. Methods of making the compounds of Formula I are also described. The invention also relates to pharmaceutical compositions comprising compounds of Formula I. Methods of using the compounds of the invention are also within the scope of the invention.
1. A compound of Formula I:
or an enantiomer or diastereomer thereof;
or a pharmaceutically acceptable salt thereof;
wherein
X is CR 1 or N;
Y is CR 2 or N;
Z is NH or O;
R 1 is alkoxy, triazolyl, oxazolyl, isoxazolyl, oxadiazolyl, or pyrimidinyl
R 2 is H, alkyl, or halo;
R 3 is H, alkyl, alkoxy, halo, triazolyl, oxazolyl, or pyrimidinyl;
R 4 is alkyl;
R 5 is pyridyl; benzoxazolyl; pyrimidinyl; pyridazinyl; quinoxalinyl; pyrazinyl; or quinazolinyl;
wherein the pyridyl; benzoxazolyl; pyrimidinyl; pyridazinyl; quinoxalinyl; pyrazinyl; or quinazolinyl is optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl; and
R 6 is H or alkyl.
2. The compound of claim 1 , wherein Z is NH.
3. The compound of claim 1 wherein Z is O.
4. The compound of claim 1 , wherein R 4 is C 1-3 alkyl.
5. The compound of claim 4 , wherein R 4 is methyl.
6. The compound of claim 1 , wherein X is CR 1 and Y is CR 2 .
7. The compound of claim 1 , wherein X is N and Y is CR 2 .
8. The compound of claim 1 , wherein X is CR 1 and Y is N.
9. The compound of claim 1 , wherein X and Y are each N.
10. The compound of claim 1 or claim 8 , wherein R 1 is alkoxy, triazolyl, or pyrimidinyl.
11. The compound of claim 10 , wherein R 1 is alkoxy.
12. The compound of claim 10 , wherein R 1 is triazolyl.
13. The compound of claim 10 , wherein R 1 is pyrimidinyl.
14. The compound of claim 13 , wherein the pyrimidinyl is halo-pyrimidinyl.
15. The compound of claim 1 or claim 8 , wherein R 1 is oxazolyl, isoxazolyl, or oxadiazolyl.
16. The compound of claim 15 , wherein oxadiazolyl is methyl-oxadiazolyl.
17. The compound of claim 1 , wherein R 2 is H.
18. The compound of claim 1 , wherein R 2 is halo.
19. The compound of claim 18 , wherein halo is F, Cl, or Br.
20. The compound of claim 1 , wherein R 2 is alkyl.
21. The compound of claim 20 , wherein alkyl is —CH 3 .
22. The compound of any one of the preceding claims, wherein R 3 is alkyl, alkoxy, halo, triazolyl, oxazolyl, or pyrimidinyl.
23. The compound of claim 22 , wherein R 3 is alkyl.
24. The compound of claim 23 , wherein alkyl is trihaloalkyl.
25. The compound of claim 23 , wherein alkyl is —CH 3 .
26. The compound of claim 22 , wherein R 3 is alkoxy.
27. The compound of claim 22 , wherein R 3 is halo.
28. The compound of claim 22 , wherein R 3 is triazolyl.
29. The compound of claim 22 , wherein R 3 is oxazolyl.
30. The compound of claim 22 , wherein R 3 is pyrimidinyl.
31. The compound of claim 1 , wherein R 5 is pyridyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
32. The compound of claim 31 , wherein alkyl is trihaloalkyl.
33. The compound of claim 31 , wherein alkyl is —CH 3 .
34. The compound of claim 1 wherein R 5 is benzoxazolyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
35. The compound of claim 34 , wherein alkyl is trihaloalkyl.
36. The compound of claim 34 , wherein alkyl is —CH 3 .
37. The compound of claim 1 , wherein R 5 is pyrimidinyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
38. The compound of claim 37 , wherein alkyl is trihaloalkyl.
39. The compound of claim 37 , wherein alkyl is —CH 3 .
40. The compound of claim 1 , wherein R 5 is pyridazinyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
41. The compound of claim 40 , wherein alkyl is trihaloalkyl.
42. The compound of claim 40 , wherein alkyl is —CH 3 .
43. The compound of claim 1 , wherein R 5 is quinoxalinyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
44. The compound of claim 43 , wherein alkyl is trihaloalkyl.
45. The compound of claim 43 , wherein alkyl is —CH 3 .
46. The compound of claim 1 , wherein R 5 is pyrazinyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
47. The compound of claim 46 , wherein alkyl is trihaloalkyl.
48. The compound of claim 46 , wherein alkyl is —CH 3 .
49. The compound of claim 1 , wherein R 5 is quinazolinyl, optionally substituted with one or two substituents independently selected from the group consisting of alkyl, halo, or phenyl.
50. The compound of claim 49 , wherein alkyl is trihaloalkyl.
51. The compound of claim 49 , wherein alkyl is —CH 3 .
52. The compound of claim 1 , wherein R 6 is H.
53. The compound of claim 1 , wherein R 6 is alkyl.
54. A compound selected from the group consisting of
Ex.
Structure
Compound Name
1
(±)-trans-(3-((4,6- dimethylpyrimidin- 2-yl)amino)-2- methylpiperidin-1- yl)(4-fluoro-2-(2H- 1,2,3-triazol-2-yl) phenyl)methanone
2
(±)-trans-(3-((4,6- dimethylpyrimidin- 2-yl)amino)-2- methylpiperidin-1- yl)(2-fluoro-6- (pyrimidin-2- yl)phenyl) methanone
3
(±)-trans-(3-((4,6- dimethylpyrimidin- 2-yl)amino)-2- methylpiperidin-1- yl)(2-fluoro-6- (2H-1,2,3-triazol-2- yl)phenyl)methanone
4
(±)-trans-(2-((2H- 1,2,3-triazol-2-yl) phenyl)(3-((4,6- dimethylpyrimidin- 2-yl)amino)-2- methylpiperidin-1- yl)methanone
5
(±)-trans-(3-((4,6- dimethylpyrimidin- 2-yl)amino)-2- methylpiperidin-1- yl)(5-fluoro-2-(2H- 1,2,3-triazol-2-yl) phenyl)methanone
6
(±)-trans-(3-((4,6- dimethylpyrimidin- 2-yl)amino)-2- methylpiperidin-1- yl)(5-methyl-2- (pyrimidin-2-yl) phenyl)methanone
7
(±)-trans-(5-methyl- 2-(pyrimidin-2-yl) phenyl)(2-methyl- 3-((6-methyl-2- (trifluoromethyl) pyrimidin-4- yl)amino)piperidin- 1-yl)methanone
8
(±)-trans-(5-methyl- 2-(2H-1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((6-methyl- 2-(trifluoromethyl) pyrimidin-4-yl) amino)piperidin-1- yl)methanone
9
(±)-trans-(5-fluoro- 2-(pyrimidin-2-yl) phenyl)(2-methyl-3- ((6-methyl-2- (trifluoromethyl) pyrimidin-4- yl)amino)piperidin- 1-yl)methanone
10
(±)-trans-(2-fluoro- 6-(2H-1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((4- (trifluoromethyl) pyrimidin-2-yl) amino)piperidin-1- yl)methanone
11
(±)-trans-(6-methyl- 2-(1H-1,2,3-triazol- 1-yl)pyridin-3- yl)(2-methyl-3-((4- (trifluoromethyl) pyrimidin-2-yl) amino)piperidin-1- yl)methanone
12
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl-3- ((5-(trifluoromethyl) pyridin-2-yl)amino) piperidin-1- yl)methanone
13
(±)-trans-(4-methyl- 2-(2H-1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1- yl)methanone
14
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2S,3R)-2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1- yl)methanone
15
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2R,3S)-2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1- yl)methanone
16
(±)-trans-(3-ethoxy- 6-methylpyridin-2- yl)(2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1- yl)methanone
17
(±)-trans-(5-chloro- 2-(2H-1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin-1- yl)methanone
18
(±)-trans-(2-methyl- 3-((5-(trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl)(6- methyl-3-(2H-1,2,3- triazol-2-yl)pyridin- 2-yl)methanone
19
(±)-trans-(5- methoxy-2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1- yl)methanone
20
(±)-trans-(3-methyl- 2-(2H-1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin-1- yl)methanone
21
(±)-trans-(3-(2H- 1,2,3-triazol-2-yl) pyridin-2-yl)(2- methyl-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin- 1-yl)methanone
22
(±)-trans-(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl)(6- methyl-3-(oxazol- 2-yl)pyridin-2-yl) methanone
23
(±)-trans-(2-methyl- 3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl)(6- methyl-3-(pyrimidin- 2-yl)pyridin-2-yl) methanone
24
(±)-trans-(5-fluoro- 2-(2H-1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl) methanone
25
((2S,3R)-2-methyl- 3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl)(6- methyl-3-(oxazol- 2-yl)pyridin-2-yl) methanone
26
((2S,3R)-2-methyl- 3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl)(5- methyl-3-(2H- 1,2,3-triazol-2-yl) pyridin-2-yl) methanone
27
((2S,3R)-2-methyl- 3-((5- (trifluoromethyl) pyridin-2-yl)amino) piperidin-1-yl)(5- methyl-3-(pyrimidin- 2-yl)pyridin-2-yl) methanone
28
(±)-trans-(3-fluoro- 2-methoxyphenyl) (2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin-1- yl)methanone
29
(±)-trans-(2- ethoxyphenyl)(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin- 1-yl)methanone
30
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(3-((5- chloropyrimidin- 2-yl)amino)-2- methylpiperidin- 1-yl)methanone
31
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-((5-methyl- pyrimidin-2-yl) amino)piperidin- 1-yl)methanone
32
(±)-trans-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(3-((5- chloropyridin-2- yl)amino)-2- methylpiperidin- 1-yl)methanone
33
(±)-trans-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(2- methyl-3-((6- (trifluoromethyl) pyridazin-3-yl) amino)piperidin- 1-yl)methanone
34
(2-(2H-1,2,3- triazol-2-yl)phenyl) ((2S,3R)-3-((5- fluoropyridin-2-yl) amino)-methyl- piperidin-1- yl)methanone
35
(±)-trans-(2-(2H- 1,2,3-triazol- 2-yl)phenyl)(2- methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) amino)piperidin- 1-yl)methanone
36
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-(pyridin-2- ylamino)piperidin- 1-yl)methanone
37
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-((5-methyl- pyridin-2-yl) amino)piperidin- 1-yl)methanone
38
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-((5- (trifluoromethyl) pyrazin-2-yl)amino) piperidin-1- yl)methanone
39
(±)-trans-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(2- methyl-3- (quinazolin-2- ylamino)piperidin- 1-yl)methanone
40
(±)-trans-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(3-((5- fluoropyrimidin- 2-yl)amino)-2- methylpiperidin- 1-yl)methanone
41
(±)-trans-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(3-(benzo [d]oxazol-2-ylamino)- 2-methylpiperidin- 1-yl)methanone
42
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(3-((5- bromopyridin-2- yl)amino)-2- methylpiperidin- 1-yl)methanone
43
(±)-trans-(3-((5- bromopyridin-2-yl) amino)-2-methyl- piperidin-1-yl)(3- fluoro-2-methoxy- phenyl)methanone
44
(±)-trans-(3-(5- bromopyridin-2- yl)amino)-2-methyl- piperidin-1-yl)(2- ethoxyphenyl) methanone
45
(±)-trans-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(3-((5- chlorobenzo[d] oxazol-2-yl) amino)-2-methyl- piperidin-1-yl) methanone
46
(±)-trans-(3-((5- chlorobenzo[d] oxazol-2-yl)amino)- 2-methylpiperidin- 1-yl)(2-ethoxy- phenyl)methanone
47
(±)-trans-(3-((5- chlorobenzo[d] oxazol-2-yl) amino)-2-methyl- piperidin-yl)(3- fluoro-2-methoxy- phenyl)methanone
48
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-(quinoxalin-2- ylamino)piperidin- 1-yl)methanone
49
(±)-trans-((2- ethoxyphenyl)(2- methyl-3- (quinoxalin-2- ylamino)piperidin- 1-yl)methanone
50
(±)-trans-(3-fluoro- 2-methoxyphenyl) (2-methyl-3- (quinoxalin-2- ylamino)piperidin- 1-yl)methanone
51
(±)-trans-(2-(2H- 1,2,3-triazol-2-yl) phenyl)(2-methyl- 3-((4-phenyl- pyrimidin-2-yl) amino)piperidin- 1-yl)methanone
52
(±)-trans-(3-fluoro- 2-methoxyphenyl) (2-methyl-3-((4- phenylpyrimidin- 2-yl)amino) piperidin-1-yl) methanone
53
(±)-trans-(2- ethoxyphenyl)(2- methyl-3-((4- phenyl-pyrimidin- 2-yl)amino) piperidin-1-yl) methanone
54
(±)-cis-(3- fluoro-2- methoxyphenyl) (2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin- 1-yl)methanone
55
(±)-cis-(2-ethoxy- phenyl)(2-methyl- 3-((5-(trifluoro- methyl)pyridin- 2-yl)amino) piperidin-1- yl)methanone
56
(±)-cis-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin- 1-yl)methanone
57
(±)-cis-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(3-((5- bromopyridin-2- yl)amino)-2- methylpiperidin- 1-yl)methanone
58
(±)-cis-(3-(5- bromopyridin-2-yl) amino)-2-methyl- piperidin-1-yl)(3- fluoro-2-methoxy- phenyl)methanone
59
(±)-cis-(3-(5- bromopyridin-2- yl)amino)-2- methylpiperidin- 1-yl)(2-ethoxy- phenyl)methanone
60
(±)-cis-((2-(2H- 1,2,3-triazol-2- yl)phenyl)(3-((5- chlorobenzo[d] oxazol-2-yl)amino)- 2-methylpiperidin- 1-yl)methanone
61
(±)-cis-(3-((5- chlorobenzo[d] oxazol-2- yl)amino)-2- methylpiperidin- 1-yl)(2-ethoxy- phenyl)methanone
62
(±)-cis-(3-((5- chlorobenzo[d] oxazol-2- yl)amino)-2- methylpiperidin- 1-yl)(3-fluoro-2- methoxyphenyl) methanone
63
(±)-cis-(2-(2H- 1,2,3-triazol-2- yl)phenyl)(2- methyl-3- (quinoxalin-2- ylamino)piperidin- 1-yl)methanone
64
(±)-cis-(3-fluoro- 2-methoxyphenyl) (2-methyl-3- (quinoxalin-2- ylamino)piperidin- 1-yl)methanone
65
(±)-cis-(2-ethoxy- phenyl)(2-methyl- 3-(quinoxalin-2- ylamino)piperidin- 1-yl)methanone
66
(±)-cis-(2-(2H- 1,2,3-triazol- 2-yl)phenyl) (2-methyl-3- ((4-phenyl- pyrimidin-2- yl)amino) piperidin-1- yl)methanone
67
(±)-cis-(3-fluoro-2- methoxyphenyl)(2- methyl-3-((4- phenylpyrimidin-2- yl)amino)piperidin- 1-yl)methanone
68
(±)-cis-(2-ethoxy- phenyl)(2-methyl- 3-((4-phenyl- pyrimidin-2-yl) amino)piperidin- 1-yl)methanone
69
(6-methyl-2-(2H- 1,2,3-triazol-2-yl) pyridin-3-yl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrimidin- 2-yl)amino) piperidin-1-yl) methanone
70
(6-methyl-2-(1H- 1,2,3-triazol-1-yl) pyridin-3-yl)(2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) amino)piperidin-1- yl)methanone
71
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)(2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) amino)piperidin- 1-yl)methanone
72
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)amino)piperidin- 1-yl)(5-methyl-3- (2H-1,2,3-triazol-2- yl)pyridin-2-yl) methanone
73
((2S,3R)-3-(benzo [d]oxazol-2-ylamino)- 2-methylpiperidin-1- yl)(5-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin-2- yl)methanone
74
(6-methyl-2-(2H- 1,2,3-triazol-2-yl) pyridin-3-yl) (2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)amino)piperidin- 1-yl)methanone
75
((2S,3R)-3-(benzo [d]oxazol-2- ylamino)-2-methyl- piperidin-1-yl)(6- methyl-2-(2H-1,2,3- triazol-2-yl)pyridin- 3-yl)methanone
76
((2S,3R)-3-(benzo [d]oxazol-2- ylamino)-2-methyl- piperidin-1-yl) (6-methyl-2-(1H- 1,2,3-triazol-1-yl) pyridin-3-yl) methanone
77
((2S,3R)-3-((5- chloropyridin-2-yl) amino)-2-methyl- piperidin-1-yl)(5- methyl-3-(oxazol- 2-yl)pyridin-2-yl) methanone
78
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrimidin- 2-yl)amino) piperidin-1-yl)(6- methyl-3- (pyrimidin-2-yl) pyridin-2-yl) methanone
79
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)(2S,3R)-2- methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)amino) piperidin-1-yl) methanone
80
((2S,3R)-3-((5- bromopyridin-2-yl) amino)-2-methyl- piperidin-1-yl)(5- methyl-3-(oxazol- 2-yl)pyridin-2-yl) methanone
81
((2S,3R)-3-(benzo[d] oxazol-2-ylamino)-2- methylpiperidin-1- yl)(6-methyl-3- (pyrimidin-2-yl) pyridin-2-yl) methanone
82
(4-methoxy-2- (2H-1,2,3-triazol- 2-yl)phenyl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin- 2-yl)amino) piperidin-1-yl) methanone
83
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)amino)piperidin- 1-yl)(5-methyl-3- (oxazol-2-yl) pyridin-2-yl) methanone
84
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)amino)piperidin- 1-yl)(6-methyl-3- (pyrimidin-2-yl) pyridin-2-yl) methanone
85
(2-(2H-1,2,3- triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl) amino)piperidin- 1-yl)methanone
86
((2S,3R)-3-((5- chloropyrazin-2- yl)amino)-2- methylpiperidin- 1-yl)(5-methyl-3- (oxazol-2-yl) pyridin-2-yl) methanone
87
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin-2- yl)amino)piperidin- 1-yl)(6-methyl-3- (2H-1,2,3-triazol-2- yl)pyridin-2-yl) methanone
88
((2S,3R)-3-(benzo[d] oxazol-2-ylamino)-2- methylpiperidin-1- yl)(5-methyl-3- (oxazol-2-yl) pyridin-2-yl) methanone
89
(5-methoxy-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2S,3R)-2- methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) amino)piperidin-1- yl)methanone
90
(5-fluoro-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl) amino)piperidin- 1-yl)methanone
91
((2S,3R)-3-((5- chloropyrimidin- 2-yl)amino)-2- methylpiperidin- 1-yl)(4-methyl-2- (2H-1,2,3-triazol- 2-yl)phenyl) methanone
92
((2S,3R)-3-((5- bromopyridin-2- yl)amino)-2- methylpiperidin- 1-yl)(5-methyl- 3-(2H-1,2,3- triazol-2-yl) pyridin-2-yl) methanone
93
(6-methyl-2-(1H- 1,2,3-triazol-1-yl) pyridin-3-yl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin- 2-yl)amino) piperidin-1-yl) methanone
94
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrimidin- 2-yl)amino) piperidin-1-yl)(5- methyl-3-(2H- 1,2,3-triazol-2- yl)pyridin-2-yl) methanone
95
(4-methoxy-2- (2H-1,2,3-triazol- 2-yl)phenyl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrimidin- 2-yl)amino) piperidin-1-yl) methanone
96
(6-methyl-2-(1H- 1,2,3-triazol-1-yl) pyridin-3-yl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)amino)piperidin- 1-yl)methanone
97
(4-methoxy-2- (2H-1,2,3-triazol- 2-yl)phenyl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin- 2-yl)amino) piperidin-1-yl) methanone
98
(6-methyl-2-(2H- 1,2,3-triazol-2-yl) pyridin-3-yl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin- 2-yl)amino) piperidin-1-yl) methanone
99
((2S,3R)-3-((5- chloropyridin-2- yl)amino)-2- methylpiperidin- 1-yl)(4-methyl- 2-(2H-1,2,3- triazol-2-yl) phenyl) methanone
100
(2-(2H-1,2,3- triazol-2-yl) phenyl)((2S,3R)- 3-((5-chloro- pyridin-2-yl) amino)methyl- piperidin-1-yl) methanone
101
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrimidin- 2-yl)oxy)piperidin- 1-yl)(5-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin- 2-yl)methanone
102
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) oxy)piperidin-1- yl)methanone
103
(2-(2H-1,2,3- triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) oxy)piperidin-1- yl)methanone
104
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrimidin- 2-yl)oxy)piperidin- 1-yl)(6-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin- 2-yl)methanone
105
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)oxy)piperidin- 1-yl)(5-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin-2-yl) methanone
106
(2-(2H-1,2,3- triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)oxy) piperidin-1-yl) methanone
107
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyrazin-2- yl)oxy)piperidin- 1-yl)(6-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin- 2-yl)methanone
108
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin- 2-yl)oxy)piperidin- 1-yl)(6-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin- 2-yl)methanone
109
(±)-trans-(2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl) oxy)piperidin- 1-yl)(6-methyl- 3-(2H-1,2,3- triazol-2-yl) pyridin-2-yl) methanone
110
(2-(2H-1,2,3- triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl)oxy) piperidin-1-yl) methanone
111
((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin-2- yl)oxy)piperidin- 1-yl)(5-methyl-3- (2H-1,2,3-triazol- 2-yl)pyridin- 2-yl)methanone
112
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl)oxy) piperidin-1-yl) methanone
113
(4-methyl-2-(2H- 1,2,3-triazol-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)oxy) piperidin-1-yl) methanone
114
(3-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 3-((5-fluoro- pyridin-2-yl) oxy)-2-methyl- piperidin-1-yl) methanone
115
(3-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 3-((5-fluoro- pyrimidin-2-yl) oxy)-2-methyl- piperidin-1-yl) methanone
116
(3-fluoro-2- (pyrimidin-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl)oxy) piperidin-1-yl) methanone
117
(3-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) oxy)piperidin- 1-yl)methanone
118
(3-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)oxy) piperidin-1-yl) methanone
119
((2S,3R)-3-(benzo [d]oxazol-2- yloxy)-2-methyl- piperidin-1-yl) (3-fluoro-2- (pyrimidin-2- yl)phenyl) methanone
120
((2S,3R)-3-(benzo [d]oxazol-2- yloxy)-2-methyl- piperidin-1-yl) (3-fluoro-2-(2H- 1,2,3-triazol-2- yl)phenyl) methanone
121
(3-fluoro-2-(2H- 1,2,3-triazol-2- yl)phenyl) ((2S,3R)-3-((5- fluoropyridin-2- yl)oxy)-2- methylpiperidin- 1-yl)methanone
122
(3-fluoro-2-(2H- 1,2,3-triazol-2- yl)phenyl) ((2S,3R)-3-((5- fluoropyrimidin- 2-yl)oxy)-2- methylpiperidin- 1-yl)methanone
123
(3-fluoro-2-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) oxy)piperidin-1- yl)methanone
124
(3-fluoro-2-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl)oxy) piperidin-1-yl) methanone
125
(3-fluoro-2-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)oxy) piperidin-1-yl) methanone
126
((2S,3R)-3-(benzo [d]oxazol-2- yloxy)-2-methyl- piperidin-1-yl)(3- fluoro-2-(2H-1,2,3- triazol-2-yl) phenyl)methanone
127
((2S,3R)-3-(benzo [d]oxazol-2-yloxy)- 2-methylpiperidin- 1-yl)(2-fluoro-6- (2H-1,2,3-triazol- 2-yl)phenyl) methanone
128
(2-fluoro-6-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 3-((5-fluoro- pyridin-2-yl)oxy)- 2-methylpiperidin- 1-yl)methanone
129
(2-fluoro-6-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 3-((5-fluoro- pyrimidin-2-yl) oxy)-2-methyl- piperidin-1- yl)methanone
130
(2-fluoro-6-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) oxy)piperidin-1- yl)methanone
131
(2-fluoro-6-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl)oxy) piperidin-1-yl) methanone
132
(2-fluoro-6-(2H- 1,2,3-triazol-2- yl)phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)oxy) piperidin-1- yl)methanone
133
(2-fluoro-6- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl)oxy) piperidin-1- yl)methanone
134
(2-fluoro-6- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) oxy)piperidin-1- yl)methanone
135
(2-fluoro-6- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrimidin-2-yl) oxy)piperidin-1- yl)methanone
136
(2-fluoro-6- (pyrimidin-2-yl) phenyl)((2S,3R)- 3-((5-fluoro- pyrimidin-2-yl) oxy)-2-methyl- piperidin-1- yl)methanone
137
(2-fluoro-6- pyrimidin-2-yl) phenyl)((2S,3R)- 3-((5-fluoro- pyridin-2-yl) oxy)-2-methyl- piperidin-1- yl)methanone
138
(5-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) oxy)piperidin-1- yl)methanone
139
(4-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) oxy)piperidin-1- yl)methanone
140
(4-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) oxy)piperidin-1- yl)methanone
141
(4-fluoro-2- (pyrimidin-2-yl) phenyl)((2S,3R)- 3-((5-fluoro- pyridin-2-yl)oxy)- 2-methylpiperidin- 1-yl)methanone
142
(3-fluoro-2-(5- fluoropyrimidin- 2-yl)phenyl) ((2S,3R)-2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl)oxy) piperidin-1-yl) methanone
143
((2S,3R)-2- methyl-3-((5- (trifluoromethyl) pyridin-2-yl) oxy)piperidin- 1-yl)(2- (pyrimidin-2- yl)phenyl) methanone
144
(2-(3-methyl- 1,2,4-oxadiazol- 5-yl)phenyl) ((2S,3R)-2-methyl- 3-((5-(trifluoro- methyl)pyridin-2- yl)amino)piperidin- 1-yl)methanone
145
(4-fluoro-2-(3- methyl-1,2,4- oxadiazol-5-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyridin-2-yl) amino)piperidin- 1-yl)methanone
146
(3-fluoro-2-(3- methyl-1,2,4- oxadiazol-5-yl) phenyl)((2S,3R)- 2-methyl-3-((5- (trifluoromethyl) pyrazin-2-yl) amino)piperidin- 1-yl)methanone
55. A pharmaceutical composition comprising a compound according claim 1 and at least one pharmaceutically acceptable excipient.
56. A method of treating a subject suffering from or diagnosed with a disease, disorder, or medical condition mediated by orexin receptor activity, wherein the disease, disorder, or medical condition is mood disorders, post-traumatic stress disorder, panic disorders, attention deficit disorders, cognitive deficiencies, or substance abuse, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .
57. The method of claim 56 , wherein the disease, disorder, or medical condition is mood disorders.