Deuterated analogs of MK2 inhibitors and uses thereof
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. A compound of Formulae IV, IV′, or IV″:
or a pharmaceutically acceptable salt thereof, whererin:
each of R 7 , R 7′ , R 8 , R 8′ , R 8″ , and R 9 is independently selected from hydrogen or deuterium;
provided that at least one of R 7 , R 7′ , R 8 , R 8′ , R 8″ , and R 9 is deuterium.
2. The compound according to claim 1 , wherein the compound is selected from:
Formula
Formula
Formula
IV
IV′
IV″
R 7
R 7′
R 8
R 8′
R 8″
R 9
IV-1
IV′-1
IV″-1
H
H
D
H
H
H
IV-2
IV′-2
IV″-2
H
H
H
D
H
H
IV-3
IV′-3
IV″-3
H
H
H
H
D
H
IV-4
IV′-4
IV″-4
H
H
D
D
H
H
IV-5
IV′-5
IV″-5
H
H
D
H
D
H
IV-6
IV′-6
IV″-6
H
H
H
D
D
H
IV-7
IV′-7
IV″-7
H
H
D
D
D
H
IV-8
IV′-8
IV″-8
H
D
H
H
H
H
IV-9
IV′-9
IV″-9
H
D
D
H
H
H
IV-10
IV′-10
IV″-10
H
D
H
D
H
H
IV-11
IV′-11
IV″-11
H
D
H
H
D
H
IV-12
IV′-12
IV″-12
H
D
D
D
H
H
IV-13
IV′-13
IV″-13
H
D
D
H
D
H
IV-14
IV′-14
IV″-14
H
D
H
D
D
H
IV-15
IV′-15
IV″-15
H
D
D
D
D
H
IV-16
IV′-16
IV″-16
D
H
H
H
H
H
IV-17
IV′-17
IV″-17
D
H
D
H
H
H
IV-18
IV′-18
IV″-18
D
H
H
D
H
H
IV-19
IV′-19
IV″-19
D
H
H
H
D
H
IV-20
IV′-20
IV″-20
D
H
D
D
H
H
IV-21
IV′-21
IV″-21
D
H
D
H
D
H
IV-22
IV′-22
IV″-22
D
H
H
D
D
H
IV-23
IV′-23
IV″-23
D
H
D
D
D
H
IV-24
IV′-24
IV″-24
D
D
H
H
H
H
IV-25
IV′-25
IV″-25
D
D
D
H
H
H
IV-26
IV′-26
IV″-26
D
D
H
D
H
H
IV-27
IV′-27
IV″-27
D
D
H
H
D
H
IV-28
IV′-28
IV″-28
D
D
D
D
H
H
IV-29
IV′-29
IV″-29
D
D
D
H
D
H
IV-30
IV′-30
IV″-30
D
D
H
D
D
H
IV-31
IV′-31
IV″-31
D
D
D
D
D
H
IV-32
IV′-32
IV″-32
H
H
H
H
H
D
IV-33
IV′-33
IV″-33
H
H
D
H
H
D
IV-34
IV′-34
IV″-34
H
H
H
D
H
D
IV-35
IV′-35
IV″-35
H
H
H
H
D
D
IV-36
IV′-36
IV″-36
H
H
D
D
H
D
IV-37
IV′-37
IV″-37
H
H
D
H
D
D
IV-38
IV′-38
IV″-38
H
H
H
D
D
D
IV-39
IV′-39
IV″-39
H
H
D
D
D
D
IV-40
IV′-40
IV″-40
H
D
H
H
H
D
IV-41
IV′-41
IV″-41
H
D
D
H
H
D
IV-42
IV′-42
IV″-42
H
D
H
D
H
D
IV-43
IV′-43
IV″-43
H
D
H
H
D
D
IV-44
IV′-44
IV″-44
H
D
D
D
H
D
IV-45
IV′-45
IV″-45
H
D
D
H
D
D
IV-46
IV′-46
IV″-46
H
D
H
D
D
D
IV-47
IV′-47
IV″-47
H
D
D
D
D
D
IV-48
IV′-48
IV″-48
D
H
H
H
H
D
IV-49
IV′-49
IV″-49
D
H
D
H
H
D
IV-50
IV′-50
IV″-50
D
H
H
D
H
D
IV-51
IV′-51
IV″-51
D
H
H
H
D
D
IV-52
IV′-52
IV″-52
D
H
D
D
H
D
IV-53
IV′-53
IV″-53
D
H
D
H
D
D
IV-54
IV′-54
IV″-54
D
H
H
D
D
D
IV-55
IV′-55
IV″-55
D
H
D
D
D
D
IV-56
IV′-56
IV″-56
D
D
H
H
H
D
IV-57
IV′-57
IV″-57
D
D
D
H
H
D
IV-58
IV′-58
IV″-58
D
D
H
D
H
D
IV-59
IV′-59
IV″-59
D
D
H
H
D
D
IV-60
IV′-60
IV″-60
D
D
D
D
H
D
IV-61
IV′-61
IV″-61
D
D
D
H
D
D
IV-62
IV′-62
IV″-62
D
D
H
D
D
D
IV-63
IV′-63
IV″-63
D
D
D
D
D
D.
3. A pharmaceutically acceptable composition comprising the compound according to any one of claims 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
4. A method for inhibiting MK2 kinase, or a mutant thereof, activity in a biological sample comprising the step of contacting said biological sample with a compound according to any one of claims 1 .
5. A method for treating an MK2-mediated disease or disorder in a patient in need thereof, comprising the step of administering to said patient the composition according to claim 3 .
6. The compound according to claim 1 , wherein each of R 7 and R 7″ is deuterium.
7. The compound according to claim 1 , wherein each of R 8 , R 8′ , and R 8″ is deuterium.
8. The compound according to claim 6 , wherein each of R 8 , R 8′ , and R 8″ is deuterium.
9. The compound according to claim 7 , wherein R 9 is deuterium.
10. The compound according to claim 6 , wherein R 9 is deuterium.
11. The compound according to claim 7 , wherein R 9 is deuterium.
12. The compound according to claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutically acceptable composition comprising the compound according to claim 12 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.