Adamantanyl-substituted benzamide compounds and their use as P2X
The present invention relates to adamantanyl-substituted benzamide compounds and their use as antagonists of the P2X 7 purinoreceptor. The invention further relates to methods for the treatment of disease and conditions associated with the P2X 7 purinoreceptor.
1 . A compound of the general formula (I):
or a pharmaceutically acceptable salt, hydrate, derivative, solvate, or tautomer thereof, wherein:
R 1 , R 2 and R 3 are independently selected from the group consisting of: hydrogen, hydroxy and halogen;
n is an integer between 0 and 4;
X is selected from the group consisting of: NH, O and S;
R is:
wherein each R 4 is independently selected from the group consisting of: halogen, hydroxy, methoxy and amino; and
m is 2,
with the proviso that at least one of R 1 , R 2 and R 3 is F.
2 . The compound of claim 1 , wherein R 1 , R 2 and R 3 are independently selected from hydrogen and halogen.
3 . The compound of claim 2 , wherein R 1 , R 2 and R 3 are all F.
4 . The compound of claim 1 , wherein n is an integer between 1 and 4.
5 . The compound claim 1 , wherein X is NH.
6 . The compound of claim 1 , wherein each R 4 is independently selected from the group consisting of: halogen, hydroxy and methoxy.
7 . The compound of claim 1 , wherein one R 4 is methoxy and the other R 4 is Cl.
8 . The compound according to claim 1 , wherein R is selected from the group consisting of:
9 . The compound according to claim 1 , wherein R is selected from the group consisting of:
10 . A compound according to claim 1 having a structure selected from the group consisting of:
11 . A compound of claim 1 , having a structure
12 . A pharmaceutical composition comprising a compound of formula (I) according to claim 1 , together with a pharmaceutically acceptable carrier, diluent or excipient.