3-phenyl-pyrazole derivatives as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto

• US 8,785,441 B2
• Filed: 09/14/2012
• Issued: 07/22/2014
• Est. Priority Date: 11/19/2004
• Status: Active Grant

• Current Assignee: Arena Pharmaceuticals Incorporated
• Original Assignee: Arena Pharmaceuticals Incorporated
• Inventors: Teegarden, Bradley, Xiong, Yifeng, Strah-Pleynet, Sonja, Jayakumar, Honnappa, Dosa, Peter I., Feichtinger, Konrad, Casper, Martin, Lehmann, Juerg, Jones, Robert M., Unett, David J., Choi, Jin Sun Karoline
• Primary Examiner(s): Young, Shawquia
• Application Number:
  US13/616,842
• Publication Number:
  US 20130237540A1
• Time in Patent Office: 676 Days
• Field of Search: 514/236.5
• US Class Current: 514/236.5
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 25/28 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/16 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/08 : Bridged systems
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to certain 3-phenyl-pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT_2A serotonin receptor.

Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette'"'"'s syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT_2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

Claims

1. A method for treating a 5-HT_2A mediated disorder selected from the group consisting of coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, and atrial fibrillation in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

2. A method for treating a condition associated with platelet aggregation selected from the group consisting of claudication, peripheral artery disease, vasoconstriction, vasospasm, arterial occlusion, thrombosis, and stroke in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

10. The method according to claim 2, wherein said condition associated with platelet aggregation is claudication.

11. The method according to claim 2, wherein said condition associated with platelet aggregation is peripheral artery disease.

12. The method according to claim 2, wherein said condition associated with platelet aggregation is vasoconstriction.

13. The method according to claim 2, wherein said condition associated with platelet aggregation is vasospasm.

14. The method according to claim 2, wherein said condition associated with platelet aggregation is arterial occlusion.

15. The method according to claim 2, wherein said condition associated with platelet aggregation is thrombosis.

16. The method according to claim 2, wherein said condition associated with platelet aggregation is stroke.

3. A method for reducing the risk of blood clot formation in an angioplasty or coronary bypass surgery individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

4. A method for reducing the risk of blood clot formation in an individual suffering from atrial fibrillation, comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

5. A method for treating a sleep disorder in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

6. A method for treating a sleep disorder in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

7. A method for treating progressive multifocal leukoencephalopathy in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound having the structure

8. A method for treating hypertension in an individual comprising administering to the individual in need thereof a therapeutically effective amount of a compound having the structure

9. A method for treating pain in an individual comprising administering to the individual in need thereof a therapeutically effective amount of a compound having the structure