Piperazine derivatives for treating disorders

Patent metadata

Field	Value
Publication number	US-9796707-B2
Application number	US-201715609596-A
Country	US
Kind code	B2
Filing date	May 31, 2017
Priority date	Apr 17, 2014
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

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.

First claim

The invention claimed is:

1. A method of treating cancer, 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 cancer comprises prostate cancer or breast cancer.

Assignees

• Univ Nottingham
• Newsouth Innovations Pty Ltd

Inventors

• Bates David
• Morris Jonathan

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title