IP Library › Granted Patent US 7,217,732
Granted Patent B2
US 7,217,732 · App. 10/464,174 · Granted May 15, 2007

Cannabinoid receptor agonists

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Quick Facts
Patent No.
US 7,217,732
App. No.
10/464,174
Granted
May 15, 2007
Kind
B2
Abstract

A compound of the formula or a pharmaceutically acceptable salt thereof, wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , L 1 , L 2 , M, n, p, X, Y and Z are as described in the specification; pharmaceutical compositions thereof, methods of making said pharmaceutical compositions; and methods of use thereof.

Claims (508)

1. A compound represented by the structural formula:

or a pharmaceutically acceptable salt or solvate thereof; wherein:

R 1 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, haloalkyl, —N(R 7 ) 2 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein the term “substituted” means being substituted with (X) p ;

R 2 is selected from the group consisting of hydogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, haloalkyl, —N(R 7 ) 2 , substituted or unsubstituted cyoloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein the term “substituted” means being substituted with (X) p ;

R 3 is selected from the group consisting of alkyl, heteroalkyl, aryl, hetroaryl, Br, Cl, F, CF 3 , OCF 2 H, OCF 3 , and alkoxy, wherein R 3 can be the same or different and is independently selected when n>1;

R 4 is selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein the term “substituted” means being substituted with (X) p ;

R 5 and R 6 , which can be the same or different, are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein the term “substituted” means being substituted with (X) p ;

R 7 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, or two R 7 groups can form a ring of 4–7 carbon atoms, wherein the term “substituted” means being substituted with (X) p ;

L 1 is selected from the group consisting of —S(O 2 )—, —S(O)—, and —S—;

L 2 is selected from the group consisting of —S(O 2 )—, —S(O)—, —S—, and —C(O)—;

M is

n is 0–4;

p is 0–5;

X can be the same or different and is selected from the group consisting of Br, Cl, F, CF 3 , OH, OCF 2 H, OCF 3 , alkoxy, alkyl, cycloalkyl, —O-cycloalkyl, heteroalkyl, —C(O)N(R 7 ) 2 , —S(O 2 )R 2 , and —OS(O 2 )R 2 , wherein X is independently selected when p>1;

Y is —S(O 2 )— and

Z is selected from the group consisting of a covalent bond, —CH 2 —, —S(O 2 )—, and —C(O)—, with the following proviso:

when Z is a covalent bond, R 2 is directly linked to the nitrogen atom shown in formula I.

2. A compound according to claim 1 , wherein L 1 is —S(O 2 )—.

3. A compound according to claim 1 , wherein L 2 is —S(O 2 )—.

4. A compound according to claim 1 , wherein R 1 is CH 3 or CF 3 .

5. A compound according to claim 1 , wherein R 5 and R 6 , which can be the same or different, are H or CH 3 .

6. A compound according to claim 1 , wherein n is 0.

7. A compound according to claim 1 , wherein X is Cl.

8. A compound according to claim 1 , wherein Z is a covalent bond, n is 0, R 2 is H, and R 1 , R 4 , R 5 , R 6 , M, L 1 , L 2 , p, Y and X are defined in the following table:

R 4 (with liking

M (with linking points

#

R 1

R 5 , R 6

point to L 2 )

to L 1 , L 2 and X)

L 1

L 2

Y

p, X

1

CH 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

2

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—C(O)—

0

3

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

4

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—C(O)—

0

5

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

6

CH 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

1, Cl

7

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

1, Cl

8

CH 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—S(O 2 )—

0

9

CF 3

CH 3 , H

—S(O 2 )—

—C(O)—

0

10

CF 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—C(O)—

0

11

CF 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—C(O)—

0

12

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

1, F

13

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

14

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—C(O)—

0

15

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—C(O)—

0

16

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

17

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

18

CF 3

CH 3 , H

—S(O 2 )—

—C(O)—

0

19

CF 3

CH 3 , H

—CH 2 —

—SO 2 —

—SO 2 —

0

20

CF 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—C(O)—

0

21

CH 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—S(O 2 )—

0

22

CF 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—S(O 2 )—

0

23

CF 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—C(O)—

0

24

CH 3

CH 3 , CH 3

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

25

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

26

CF 3

CH 3 , CH 3

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

27

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—C(O)—

0

28

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

29

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

30

CH 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—S(O 2 )—

0

31

CF 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

32

CF 3

CH 3 , H

—C(O)—

—S(O 2 )—

—C(O)—

0

33

CF 3

CH 3 , H

—S(O 2 )—

—C(O)—

0

34

CH 3

CH 3 , H

—C(O)—

—S(O 2 )—

—S(O 2 )—

0

35

CF 3

CH 3 , CH 3

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

36

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

37

CH 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

38

CH 3

CH 3 , H

—O—

—S(O 2 )—

0

39

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

40

CF 3

H, H

—S(O 2 )—

—S(O 2 )—

—C(O)—

0

41

CF 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

1, Cl

42

CH 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

43

CF 3

CH 3 , H

—C(O)—

—S(O 2 )—

—C(O)—

0

44

CH 3

CH 3 , H

—C(O)—

—S(O 2 )—

—S(O 2 )—

0

45

CH 3

CH 3 , H

—CH 2 —

—O—

—S(O 2 )—

0

46

CF 3

CH 3 , H

—SO 2 —

—SO—

—C(O)—

CH 3

47

CF 3

CH 3 , H

—CH 2 —

—S(O 2 )—

—C(O)—

0

48

CF 3

CH 3 , H

—C(O)—

—O—

—C(O)—

0

49

CF 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

50

CF 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

51

CF 3

CH 3 , H

—S(O 2 )—

—C(O)—

—C(O)—

0

52

CF 3

CH 3 , H

—C(O)—

—S—

—C(O)—

0

53

CH 3

CH 3 , H

—C(O)—

—S—

—S(O 2 )—

0

54

CF 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

55

CH 3

H, H

—S(O 2 )—

—CH 2 —

—S(O 2 )—

1, F

56

CH 3

CH 3 , H

—C(O)—

—S(O 2 )—

—S(O 2 )—

0

57

CH 3

CH 3 , H

—S(O 2 )—

—S(O 2 )—

0

58

CH 3

CH 3 , H

—S(O 2 )—

—CH 2 —

—S(O 2 )—

0

59

CH 3

CH 3 , H

—C(O)—

—O—

—S(O 2 )—

0

60

CH 3

CH 3 , H

—S(O 2 )—

—C(O)—

—S(O 2 )—

1, Cl

61

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

62

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

63

CF 3

H, H

—S(O 2 )—

—S(O 2 )—

—S(O 2 )—

0

64

CF 3

CH 3 , H

—S(O 2 )—

—S—

—C(O)—

0

65

CF 3

H, H

—S(O 2 )—

—CH 2 —

—S(O 2 )—

1, F

66

CH 3 , H

—S(O 2 )—

—CH 2 —

—CH 2 —

F.

9. The compound according to claim 1 having the following formula:

10. The compound according to claim 1 having the following formula:

11. The compound according to claim 1 having the following formula:

12. The compound according to claim 1 having the following formula:

13. The compound according to claim 1 having the following formula:

14. The compound according to claim 1 having the following formula:

15. The compound according to claim 1 having the following formula:

16. The compound according to claim 1 having the following formula:

17. The compound according to claim 1 having the following formula:

18. The compound according to claim 1 having the following formula:

19. The compound according to claim 1 having the following formula:

20. The compound according to claim 1 having the following formula:

21. The compound according to claim 1 having the following formula:

22. The compound according to claim 1 having the following formula:

23. The compound according to claim 1 having the following formula:

24. The compound according to claim 1 wherein said alkyl is in the various definitions of lower alkyl.

25. A pharmaceutical composition comprising one or more compounds according to claim 1 .

26. The pharmaceutical composition according to claim 25 , further comprising one or more pharmaceutically acceptable carriers.

27. A method of preparing the pharmaceutical composition of claim 26 , said method comprising contacting said one or more compounds of formula I with said one or more pharmaceutically acceptable carriers.

28. The compound according to claim 1 having the following formula:

Assignments (1)
CHANGE OF NAME Recorded Aug 30, 2012
From: SCHERING CORPORATION
To: MERCK SHARP & DOHME CORP.
Reel/Frame 028884/0151 →