Piperazine derivatives for treating disorders
Anti-angiogenic treatments, treatments of hyperpermeability disorders, treatments of neuropathic and neurodegenerative disorders, pain treatments, methods of reducing the risk of pre-eclampsia and compounds for use in such methods are described.
1. A method of treating pain, comprising administering to a subject in need thereof a compound of Formula (I)
or a pharmaceutically acceptable salt thereof;
wherein:
n=1, 2, 3 or 0;
R 1 =a 4- to 8-membered carbocyclic group, which may have one or more substituent;
a 4- to 8-membered heterocyclic group comprising one oxygen atom, which may have one or more substituent; a 4- to 8-membered heterocyclic group comprising one nitrogen atom, which may have one or more substituent, a 4- to 8-membered heterocyclic group comprising one nitrogen atom and one oxygen atom which may have one or more substituent; a 4- to 8-membered heterocyclic group comprising two nitrogen atoms which may have one or more substituent; a 4- to 8-membered heterocyclic group comprising three nitrogen atoms which may have one or more substituent, or a condensed aromatic heterocyclic group, which may have one or more substituent;
X═CH, NH or N;
Y═CH, NH or N;
Z═O, S, N or NH; and
R 2 ═H, a C 1-6 alkyl group; a phenyl group; a 4- to 8-membered heterocyclic group; or a condensed aromatic heterocyclic group, each of which may have one or more substituent.
2. A method according to claim 1 , wherein
n=1, 2, 3 or 0;
R 1 =a 4- to 8-membered carbocyclic group, which may have one or more substituent;
a 4- to 8-membered heterocyclic group having one nitrogen atom, which may have one or more substituent, a 4- to 8-membered heterocyclic group comprising one nitrogen atom and one oxygen atom which may have one or more substituent, or a 4- to 8-membered heterocyclic group comprising two nitrogen atoms which may have one or more substituent;
X═CH or N;
Y═CH or N;
Z═O, S or NH; and
R 2 =a phenyl group; a 4- to 8-membered heterocyclic group or a condensed aromatic heterocyclic group.
3. A method according to claim 1 , wherein R 1 represents a 4- to 8- membered heterocyclic group comprising one nitrogen atom, which may have one or more substituent.
4. A method according to claim 1 , wherein R 1 represents a 6-membered heteroaromatic group comprising one nitrogen atom, which may have one or more substituent.
5. A method according to claim 1 , wherein R 1 represents a 2-, 3- or 4-pyridyl group, each of which may have one or more substituent.
6. A method according to claim 1 , wherein R 1 represents a pyrimidinyl group, which may have one or more substituent.
7. A method according to claim 1 , wherein R 1 represents a 4- to 8-membered carbocyclic group, which may have one or more substituent.
8. A method according to claim 1 , wherein R 1 represents a phenyl group, which may have one or more substituent.
9. A method according to claim 1 , wherein R 2 represents a nitrogen- or oxygen-containing 4- to 8-membered heteroaromatic ring, which may have one or more substituent.
10. A method according to claim 1 , wherein R 2 represents a nitrogen-containing 4- to 8-membered heteroaromatic ring, which may have one or more substituent.
11. A method according to claim 1 , wherein R 2 represents a 2- or 3- or 4-pyridyl group, each of which may have one or more substituent.
12. A method according to claim 1 , wherein R 2 represents an oxygen-containing 4- to 8- membered heterocyclic ring, which may have one or more substituent.
13. A method according to claim 1 , wherein R 2 represents a 4- to 8-membered carbocyclic group, which may have one or more substituent.
14. A method according to claim 1 , wherein R 2 represents a phenyl group, which may have one or more substituent.
15. A method according to claim 1 , wherein R 2 represents H, or C 1-6 alkyl which may have one or more substituent.
16. A method according to claim 1 , wherein R 2 represents a methyl group, which may have one or more substituent.
17. A method according to claim 1 , wherein R 2 represents a tetrahydropyranyl group, which may have one or more substituent.
18. A method according to claim 1 , wherein:
X═Y═CH and Z═O;
X═Y═CH and Z═S;
X═Y═N and Z═O; or
X═N, Y═CH, and Z═O.
19. A method according to claim 1 , wherein n=1 or 2.
20. A method according to claim 1 , wherein the pain comprises non-inflammatory neuropathic or nociceptive pain.