5-halo-tryptamine derivatives used as ligands on the 5-HT6and/or 5-HT7serotonin receptors

• US 7,098,233 B2
• Filed: 06/17/2002
• Issued: 08/29/2006
• Est. Priority Date: 06/21/2001
• Status: Expired due to Fees

• Current Assignee: Sigma-Tau Industrie Farmaceutiche Riunite SPA (Alfasigma S.p.A.)
• Original Assignee: Sigma-Tau Industrie Farmaceutiche Riunite SPA (Alfasigma S.p.A.)
• Inventors: Tarzia, Giorgio, Di Cesare, Maria Assunta, Spadoni, Gilberto, Minetti, Patrizia
• Primary Examiner(s): Saeed, Kamal A.
• Application Number:
  US10/481,433
• Publication Number:
  US 20040235899A1
• Time in Patent Office: 1,534 Days
• Field of Search: 548/504, 514/415
• US Class Current: 514/415
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 209/16 Tryptamines

Abstract

Compounds of Formula (I): (I); wherein: R₁ and R₂ either the same or different, are H or linear or branched C₁–C₆ alkyl; R₃=linear or branched C₁–C₆ alkyl; R₄=halogen, and pharmaceutically acceptable salts thereof are useful as active ingredients in the preparation of medicaments used as ligands of the 5-HT₆ and/or 5-HT₇ serotoninergic receptors.

Claims

1. A method of selectively interacting with the 5-HT-₆ and/or 5-HT₇ serotonin receptors comprising administering to a subject in need thereof an effective amount of a compound of Formula (I)

2. The method according to claim 1, wherein said selective interaction treats nervous system pathologies associated with serotonin level deficit, systemic pathologies involving the cardiovascular system, and systemic pathologies involving the gastrointestinal tract.

3. The method, according to claim 2, wherein hypertension is treated.

4. The method according to claim 2, wherein irritable bowel disease is treated.

5. The method according to claim 1, wherein the method treats migraine, depression, hypertension, psychosis and symptoms arising from the desynchronisation and/or loss of circadian rhythms.

6. The method according to claim 1, wherein ligands of the 5-HT₆ serotoninergic receptor and are used in the treatment of depression, mood disorders, psychosis, schizophrenia, motor disorders, cognitive disorders, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, or Huntington'"'"'s disease.

7. The method according to claim 1, wherein in the compound of Formula (I) R₁ is the same as to R₂.

8. The according to claim 1, wherein in the compound of Formula (I), R₃ is methyl and R₄ is bromo or chloro.

9. The method according to claim 1, wherein in the compound of Formula (I) R₄ is bromo.

10. The method according to claim 9, wherein the compound is 5-bromo-2-methyl-N,N-dimethyltryptamine.

11. The method according to claim 1, wherein the compound R₄ is chloro.

12. The method according to claim 11, wherein the Formula (I) compound is 5-chloro-2-methyl-N,N-dimethyltryptamine or 5-chloro-2-ethyl-N,N-dimethyltryptamine.

13. The method according to claim 9, wherein the compounds are ligands of the 5-HT₇ serotoninergic receptor.

14. The method according to claim 11, wherein the compounds are ligands of the 5-HT₆ serotoninergic receptor.

15. The method according to claim 13 wherein the method treats depression, migraine, hypertension, assists or improves the individual learning processes or counteracts the desynchronisation of human biological rhythms giving rise to mental fatigue, depression and sleep disorders.

16. The method according to claim 14 wherein the method treats depression, mood disorders, psychosis, schizophrenia, motor disorders, cognitive disorders, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, or Huntington'"'"'s disease.

17. A compound of the formula

18. A process for the preparation of the compounds according to claim 17, according to the following scheme:

19. A pharmaceutical compositions comprising at least one compound of claim 17 as the active ingredient, admixed with a pharmaceutically acceptable vehicles and/or excipient.