CGRP antagonist compounds
The disclosures herein relate to novel compounds of Formula (1a): and salts thereof, wherein W, Z, L, R 1 and R 2 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with CGRP receptors.
1. A compound of Formula (l a):
or a salt thereof, wherein;
W is CH or N;
Z is CH or N;
R 1 is an aryl or heteroaryl group optionally substituted with one or more halo groups or C 1-3 alkyl groups which are themselves optionally substituted with one or more F atoms;
R 2 is H or C 1-3 alkyl optionally substituted with one or more F atoms;
and L is a C 4-15 linker group optionally substituted with one or more F atoms, wherein one, two or three, but not all, of the carbon atoms of the linker group may be optionally replaced by a heteroatom selected from O and N.
2. The compound according to claim 1 , which is a compound of Formula (2a):
or a salt thereof.
3. The compound according to claim 1 , which is a compound of Formula (3a):
or a salt thereof.
4. The compound according to claim 1 , which is a compound of Formula (4a):
or a salt thereof.
5. The compound according to claim 1 , or a salt thereof, wherein W is N and Z is CH.
6. The compound according to claim 1 , or a salt thereof, wherein W is CH and Z is N.
7. The compound according to claim 1 , or a salt thereof, wherein W and Z are both CH.
8. The compound according to claim 1 , or a salt thereof, wherein R 1 is a phenyl ring optionally substituted with one or more F atoms or C 1-3 B alkyl groups which are themselves optionally substituted with one or more F atoms.
9. The compound according to claim 1 , or a salt thereof, wherein R 1 is a phenyl ring optionally substituted with 1-5 F atoms.
10. The compound according to claim 1 , or a salt thereof, wherein R 2 is H or methyl.
11. The compound according to claim 1 , or a salt thereof, wherein R 2 is methyl.
12. The compound according to claim 1 , or a salt thereof, wherein L is a linker group of the formula:
wherein “r” indicates the point of attachment to the pyridine ring and “a” indicates the point of attachment to N; V, X and Y are independently selected from a bond, O, CH 2 , NH and NMe; b, c, d and e are independently 1, 2 or 3 and the dotted line indicates that a single or double bond may be present.
13. The compound according to claim 1 , or a salt thereof, wherein L is selected from the group consisting of:
—CHCHCH 2 OCH 2 CH 2 OCH 2 CH 2 —;
—CHCHCH 2 OCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 —;
—CH 2 CH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 —;
—CH 2 CH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 —;
—CHCHCH 2 OCH 2 CH 2 CH 2 CH 2 CH 2 —;
—CHCHCH 2 OCH 2 CH 2 N(CH 3 )CH 2 CH 2 —;
—CHCHCH 2 OCH 2 CH 2 NHCH 2 CH 2 —;
—CHCHCH 2 CH 2 CH 2 CH 2 N(CH 3 )CH 2 CH 2 —;
—CHCHCH 2 N(CH 3 )CH 2 CH 2 CH 2 CH 2 CH 2 —;
—CH 2 CH 2 CH 2 N(CH 3 )CH 2 CH 2 CH 2 CH 2 CH 2 —;
—CHCHCH 2 CH 2 CH 2 CH 2 NHCH 2 CH 2 —;
—CHCHCH 2 N(CH 3 )CH 2 CH 2 N(CH 3 )CH 2 CH 2 —;
—CHCHCH 2 OCH 2 CH 2 OCH 2 CH 2 CH 2 —;
—CHCHCH 2 OCH 2 CH 2 CH 2 OCH 2 CH 2 —;
—CHCHCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 —;
—CHCHCH 2 CH 2 OCH 2 CH 2 CH 2 CH 2 —;
—CHCHCH 2 CH 2 CH 2 OCH 2 CH 2 CH 2 —
and
—CHCHCH 2 OCH 2 CH 2 CH 2 CF 2 CH 2 —.
14. The compound according to claim 1 which is selected from the group consisting of:
and salts thereof.
15. The compound according to claim 1 , or a salt thereof, having CGRP receptor antagonist activity.
16. A pharmaceutical composition comprising a compound as defined in claim 1 , or a salt thereof, and a pharmaceutically acceptable excipient.
17. The compound according to claim 14 , wherein the compound is
18. The compound according to claim 14 , wherein the compound is a salt of
19. The compound according to claim 14 , wherein the compound is
20. The compound according to claim 14 , wherein the compound is a salt of
21. The compound according to claim 14 , wherein the compound is
22. The compound according to claim 14 , wherein the compound is a salt of
23. The compound according to claim 14 , wherein the compound is
24. The compound according to claim 14 , wherein the compound is a salt of
25. The compound according to claim 14 , wherein the compound is
26. The compound according to claim 14 , wherein the compound is a salt of
27. The compound according to claim 14 , wherein the compound is
28. The compound according to claim 14 , wherein the compound is a salt of
29. The compound according to claim 14 , wherein the compound is
30. The compound according to claim 14 , wherein the compound is a salt of
31. A pharmaceutical composition comprising a compound selected rom the group consisting of
and