Crystalline forms of certain 3-phenyl-pyrazole derivatives as modulators of the 5-HT;serotonin receptor useful for the treatment of disorders related thereto

• US 8,980,891 B2
• Filed: 12/16/2010
• Issued: 03/17/2015
• Est. Priority Date: 12/18/2009
• Status: Active Grant

• Current Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Original Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Inventors: Stirn, Scott, Lally, Edward A.
• Primary Examiner(s): ANDERSON, REBECCA L
• Application Number:
  US13/516,646
• Publication Number:
  US 20120252813A1
• Time in Patent Office: 1,552 Days
• Field of Search: 544/140, 514/236.5
• US Class Current: 514/236.5
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• 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: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Abstract

Provided are certain solvates of 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions comprising such solvates and methods for their use.

Claims

1. 3-Methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate with an XRPD, measured with CuKα

radiation, having peaks, in terms of 2θ

, chosen from those having about the following values;

5.0998, 18.7064, 19.1157, 19.3029, and 23.6567.

2. A pharmaceutical composition comprising a hydrate of claim 1 and at least one pharmaceutically acceptable carrier.

3. A method of treating a 5HT_2A-related disorder comprising administering to a patient having said disorder a therapeutically effective amount of a hydrate of claim 1.

4. The method according to claim 3 wherein the 5HT_2A-related disorder is selected from a condition associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, asthma or symptoms thereof, agitation or a symptom thereof, 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, sleep disorders, diabetic-related disorders and progressive multifocal leukoencephalopathy.

5. The method according to claim 4 wherein the 5HT_2A-related disorder is a condition associated with platelet aggregation.

6. A method of treating a 5HT_2A-related disorder comprising administering to a patient having said disorder a therapeutically effective amount of a pharmaceutical composition of claim 2.

7. The method according to claim 6 wherein the 5HT_2A-related disorder is selected from a condition associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, asthma or symptoms thereof, agitation or a symptom thereof, 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, sleep disorders, diabetic-related disorders and progressive multifocal leukoencephalopathy.

8. The method according to claim 7 wherein the 5HT_2A-related disorder is a condition associated with platelet aggregation.

12. The method according to claim 5, wherein the condition associated with platelet aggregation is chosen from claudication, peripheral artery disease, vasoconstriction, vasospasm, thrombosis, and stroke.

13. The method according to claim 8, wherein the condition associated with platelet aggregation is chosen from claudication, peripheral artery disease, vasoconstriction, vasospasm, thrombosis, and stroke.

9. 3-Methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate prepared by a process comprising:

adding aqueous base to a solution of 4-(2-(4-(3-methoxybenzamido)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethyl)morpholin-4-ium chloride; and

collecting the 3-methoxy-N[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate, wherein said 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl- has an XRPD, measured with CuKα

radiation, having peaks, in terms of 2θ

, chosen from those having about the following values;

5.0998, 18.7064, 19.1157, 19.3029, and 23.6567.

10. A solid pharmaceutical composition comprising 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate prepared by a process comprising:

formulating a therapeutically effective amount of 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate and at least one pharmaceutically acceptable carrier to produce a solid pharmaceutical composition, wherein said 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl- has an XRPD, measured with CuKα

radiation, having peaks, in terms of 2θ

, chosen from those having about the following values;

5.0998, 18.7064, 19.1157, 19.3029, and 23.6567.

11. The solid pharmaceutical composition according to claim 10, wherein the pharmaceutical composition is in a form chosen from powders, tablets, pills, capsules, cachets, suppositories, dispersible granules, and lozenges.