Crystalline forms of (S)-7-([1,2,4]triazolo[1,5-;]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline and use thereof

• US 8,815,894 B2
• Filed: 05/11/2010
• Issued: 08/26/2014
• Est. Priority Date: 05/12/2009
• Status: Active Grant

• Current Assignee: Consynance Therapeutics Incorporated
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Wei, Chenkou, Rosso, Victor W., Gao, Qi
• Primary Examiner(s): Northington Davis, Zinna
• Application Number:
  US12/777,840
• Publication Number:
  US 20100292250A1
• Time in Patent Office: 1,568 Days
• Field of Search: None
• US Class Current: 514/303
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• 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: C07D 471/04 : Ortho-condensed systems

Abstract

Novel [1,2,4]triazolo[1,5-a]pyridinyl-6-yl-substituted tetrahydroisoquinolines are described in the present invention. These compounds and crystalline forms SA1 and N-2 are used in the treatment of various neurological and physiological disorders. Methods of making these compounds and crystalline forms SA-1 and N-2 are also described in the present invention.

Claims

1. Crystalline Form SA-1 of

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

6. A method of treating a disorder which is created by or is dependent upon decreased availability of norepinephrine, dopamine, or serotonin, wherein the disorder is selected from the group consisting of attention deficit hyperactivity disorder (ADHD), cognition impairment, anxiety disorders, generalized anxiety disorder (GAD), panic disorder, bipolar disorder or manic depression or manic-depressive disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, social phobia, simple phobias, pre-menstrual dysphoric disorder (PMDD), social anxiety disorder (SAD), major depressive disorder (MDD), postnatal depression, dysthymia, depression associated with Alzheimer'"'"'s disease, Parkinson'"'"'s disease, or psychosis, supranuclear palsy, eating disorders, obesity, anorexia nervosa, bulimia nervosa, binge eating disorder, diabetes, ischemic diseases, pain, substance abuse disorders, chemical dependencies, nicotine addiction, cocaine addiction, amphetamine addiction, alcohol addiction, Lesch-Nyhan syndrome, neurodegenerative diseases, Parkinson'"'"'s disease, late luteal phase syndrome or narcolepsy, psychiatric symptoms, anger, rejection sensitivity, movement disorders, extrapyramidal syndrome, Tic disorders, restless leg syndrome (RLS), tardive dyskinesia, sleep related eating disorder (SRED), night eating syndrome (NES), stress urinary incontinence (SUI), migraine, neuropatheic pain, diabetic neuropathy, lower back pain, fibromyalgia syndrome (FS), osteoarthritis pain, arthritis pain, chronic fatigue syndrome (CFS), sexual dysfunction, premature ejaculation, male impotence, thermoregulatory disorders, and irritable bowel synddrome (IBS),

said method comprising:

administering to a patient in need of such treatment a therapeutically effective amount of cyrstalline form according to claim 1 or a pharmaceutically acceptable salt thereof.

7. The method according to claim 6 further comprising:

administering a therapeutically effective amount of a serotonin 1A receptor antagonist or a pharmaceutically acceptable salt thereof.

8. The method according to claim 7, wherein the serotonin 1A receptor antagonist is selected from the group consisting of WAY 100135 and spiperone.

9. The method according to claim 6 further comprising:

administering a therapeutically effective amount of a selective neurokinin-1 receptor antagonist or a pharmaceutically acceptable salt thereof.

10. The method according to claim 6 further comprising:

administering a therapeutically effective amount of a norepinephrine precursor or a pharmaceutically acceptable salt thereof.

11. The method according to claim 10, wherein the norepinephrine precursor is selected from the group consisting of L-tyrosine and L-phenylalanine.

12. A method of inhibiting synaptic norepinephrine uptake in a patient comprising:

administering to the patient a therapeutically effective inhibitory amount of a crystalline form according to claim 1 or a pharmaceutically acceptable salt thereof.

13. A method of inhibiting synaptic serotonin uptake in a patient comprising:

administering to the patient a therapeutically effective inhibitory amount of a crystalline form according to claim 1 or a pharmaceutically acceptable salt thereof.

14. A method of inhibiting synaptic dopamine uptake in a patient comprising:

administering to the patient a therapeutically effective inhibitory amount of a crystalline form according to claim 1 or a pharmaceutically acceptable salt thereof.

15. A method of suppressing the desire of humans to smoke comprising:

administering to a human in need of such suppression an effective amount, to relieve the desire to smoke, of a crystalline form according to claim 1 or a pharmaceutically acceptable salt thereof.

16. A method of suppressing the desire of humans to consume alcohol comprising:

administering to a human in need of such suppression an effective amount, to relieve the desire to consume alcohol, of a crystalline form according to claim 1 or a pharmaceutically acceptable salt thereof.

2. Substantially pure crystalline Form SA-1 of

3. The crystalline form of claim 2, wherein said Form SA-1 has a purity of at least 98 wt %.

4. The crystalline form of claim 2, wherein said Form SA-1 has a purity of at least 99 wt %.