Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity

• US 9,422,225 B2
• Filed: 09/19/2008
• Issued: 08/23/2016
• Est. Priority Date: 12/01/2005
• Status: Active Grant

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Auspex Pharmaceuticals, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Gant, Thomas G., Sarshar, Sepehr
• Primary Examiner(s): BROOKS, CLINTON A
• Application Number:
  US12/234,236
• Publication Number:
  US 20090018207A1
• Time in Patent Office: 2,895 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 2200/05 : Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/001 : Acyclic or carbocyclic compounds
• CPC Class Codes: C07C 217/74 : with rings other than six-membered aromatic rings being part of the carbon skeleton
• CPC Class Codes: C07C 235/34 : having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 255/37 : the carbon skeleton being further substituted by etherified hydroxy groups
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 65/21 : containing ether groups, groups, groups, or groups

Abstract

Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described.

Claims

1. A compound selected from the group consisting of:

2. The compound as recited in claim 1, wherein said compound is the R-enantiomer.

3. The compound as recited in claim 1, wherein said compound is the S-enantiomer.

4. The compound as recited in claim 1, wherein said compound is a hydrochloride salt.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition as recited in claim 5, formulated as a tablet or capsule.

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 2 and a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 3 and a pharmaceutically acceptable carrier.

9. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 4 and a pharmaceutically acceptable carrier.

10. The compound as recited in claim 1 wherein said compound is a mixture of enantiomers.

11. The compound as recited in claim 1, wherein sites designated as D contain deuterium enrichment of greater than 10%.

12. The compound as recited in claim 1, wherein sites designated as D contain deuterium enrichment of greater than 20%.

13. The compound as recited in claim 1, wherein sites designated as D contain deuterium enrichment of greater than 50%.

14. The compound as recited in claim 1, wherein sites designated as D contain deuterium enrichment of greater than 70%.

15. The compound as recited in claim 1, wherein sites designated as D contain deuterium enrichment of greater than 90%.

16. The compound as recited in claim 1, comprising about 10% or less by weight of the S-enantiomer.

17. The compound as recited in claim 1, comprising about 10% or less by weight of the R-enantiomer.