Growth hormone secretagogues
View Patent ↗A family of peptides and peptidomimetic compounds useful as GHS analogs according to either formula (I) or (II) as depicted below: or a pharmaceutically acceptable salts thereof, wherein the variables are as defined in the specification.
1. A compound of the formula (I)
wherein
X is
Y is H or NR 12 R 13 ;
Z is —C(O)— or —SO 2 —;
n is, independently for each occurrence. 1, 2, 3, 4, 5, 6, 7, or 8;
R 1 and R 3 each is, independently, H or (C 1 -C 4 )alkyl;
R 2 and R 4 each is, independently,
R 5 is H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, substituted (C 1 -C 6 )alkyl, substituted (C 2 -C 6 )alkenyl, substituted (C 2 -C 6 )alkynyl, aryl, alkylaryl, alkylarylalkyl or arylalkylaryl;
R 8 and R 9 each is, independently, (C 1 -C 6 )alkyl or substituted (C 1 -C 6 )alkyl;
R 6 , R 7 , R 10 , R 11 , R 12 and R 13 each is, independently, H, (C 1 -C 6 )alkyl or substituted (C 1 -C 6 )alkyl; and
Q is H or (C 1 -C 4 )alkyl;
provided that:
at least one of R 2 and R 4 is
in said compound;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , wherein
R 2 is
and
R 4 is
3. A compound according to claim 2 , wherein Z is —C(O)—.
4. A compound according to claim 3 , wherein
X is
R 6 and R 7 each is, independently, H; and
R 8 and R 9 each is, independently, CH 3 .
5. A compound of claim 4 , wherein
R 1 is H;
R 3 is H or methyl; and
R 5 is H, methyl, ethyl, isopropyl or t-butyl.
6. A compound according to claim 3 , wherein
X is
and
Y is H.
7. A compound according to claim 6 wherein
R 1 is H;
R 3 is H or methyl; and
R 5 is H, methyl, ethyl, isopropyl or t-butyl.
8. A compound according to claim 3 , wherein
X is
and
Y is NR 12 R 13 ;
wherein both R 12 and R 13 are each H.
9. A compound of claim 8 wherein
R 1 is H;
R 3 is H or methyl; and
R 5 is H, methyl, ethyl, isopropyl or t-butyl.
10. A compound according to claim 2 , wherein Z is —SO 2 —.
11. A compound according to claim 10 , wherein
X is
R 6 and R 7 each is, independently, H; and
R 8 and R 9 each is, independently, CH 3 .
12. A compound of claim 11 , wherein
R 1 is H;
R 3 is H or methyl; and
R 5 is H, methyl, ethyl, isopropyl or t-butyl.
13. A compound according to claim 10 , wherein
X is
and
Y is H.
14. A compound according to claim 13 wherein
R 1 is H;
R 3 is H or methyl; and
R 5 is H, methyl, ethyl, isopropyl or t-butyl.
15. A compound according to claim 10 , wherein
X is
and
Y is NR 12 R 13 ;
wherein both R 12 and R 13 are each H.
16. A compound of claim 15 wherein
R 1 is H;
R 3 is H or methyl; and
R 5 is H, methyl, ethyl, isopropyl or t-butyl.
17. A compound of claim 2 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
18. A compound according to claim 1 , wherein
R 2 is
and
R 4 is
19. A compound of claim 18 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
20. A compound according to claim 1 , wherein
R 2 is
and
R 4 is
21. A compound of claim 20 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
22. A compound according to claim 1 , wherein
R 2 is
R 4 is
23. A compound of claim 22 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
24. A compound according to claim 1 , wherein
R 2 is
and
R 4 is
25. A compound according to claim 24 wherein Q is H.
26. A compound of claim 25 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
27. A compound according to claim 1 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
28. A pharmaceutical compositions comprising a compound of claim 27 .
29. The composition of claim 28 , in combination with a pharmaceutically acceptable carrier.
30. A compound according to claim 27 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
31. A pharmaceutical compositions comprising a compound of claim 30 .
32. The composition of claim 31 , in combination with a pharmaceutically acceptable carrier.
33. A compound according to claim 30 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
34. A pharmaceutical compositions comprising a compound of claim 33 .
35. The composition of claim 34 , in combination with a pharmaceutically acceptable carrier.
36. A compound according to claim 33 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
37. A pharmaceutical compositions comprising a compound of claim 36 .
38. The composition of claim 37 , in combination with a pharmaceutically acceptable carrier.
39. A compound according to claim 36 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
40. A pharmaceutical compositions comprising a compound of claim 39 .
41. The composition of claim 40 , in combination with a pharmaceutically acceptable carrier.
42. A compound according to claim 39 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
43. A pharmaceutical compositions comprising a compound of claim 42 .
44. The composition of claim 43 , in combination with a pharmaceutically acceptable carrier.
45. A compound according to claim 27 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
46. A pharmaceutical compositions comprising a compound of claim 45 .
47. The composition of claim 46 , in combination with a pharmaceutically acceptable carrier.
48. A compound according to claim 27 , wherein said compound is according to the formula:
or a pharmaceutically acceptable salt thereof.
49. A pharmaceutical compositions comprising a compound of claim 48 .
50. The composition of claim 49 , in combination with a pharmaceutically acceptable carrier.