Salts of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-y1)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide and their preparation

• US 7,868,176 B2
• Filed: 09/26/2005
• Issued: 01/11/2011
• Est. Priority Date: 09/27/2004
• Status: Active Grant

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Thygesen, Mikkel Boas, Schlienger, Nathalie, Tolf, Bo-Ragnar, Berghausen, Jörg, Blatter, Fritz
• Primary Examiner(s): Andres; Janet L
• Assistant Examiner(s): Mabry; John
• Application Number:
  US11/235,381
• Publication Number:
  US 20060111399A1
• Time in Patent Office: 1,933 Days
• Field of Search: 546/224, 514/317
• US Class Current: 546/224
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular 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 25/22 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 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 9/08 Vasodilators for multiple indications
• 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: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07D 211/58 attached in position 4

Abstract

Disclosed herein are salts of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy) phenylmethyl)carbamide including the citrate, fumarate, maleate, malate, phosphate, succinate, sulphate, and edisylate salts.

Claims

1. An isolated and purified crystalline salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′

-(4-(2-methylpropyloxy)phenylmethyl)carbamide of formula I,

2. The salt of claim 1, wherein the salt is a citrate.

3. The salt of claim 2 that exhibits a X-ray powder diffraction pattern comprising peaks having d-values in angstroms of about 31.8, about 15.9, about 7.9, about 6.3, about 5.96, about 5.23, and about 4.68.

4. The salt of claim 1, wherein the salt is an edisylate (ethanedisulfonate).

5. The salt of claim 4 that exhibits a X-ray powder diffraction pattern comprising peaks having d-values in angstroms of about 10.0, about 6.05, about 5.31, about 4.97, about 4.26, and about 4.12.

7. A pharmaceutical composition comprising one or more salts of claim 1 and a pharmaceutically acceptable carrier.

8. The phatinaceutical composition of claim 7, wherein the composition is in a solid dosage form.

9. The pharmaceutical composition of claim 8, wherein the solid dosage form is suitable for oral administration.

10. The pharmaceutical composition of claim 9, wherein the amount of the salt of formula IV is from about 1 to 100 mg.

11. The salt of claim 2 that exhibits a X-ray powder diffraction pattern comprising peaks having d-values in angstroms of about 15.9, about 7.9, about 6.3, and about 4.68.

12. The salt of claim 4 that exhibits a X-ray powder diffraction pattern comprising peaks having d-values in angstroms of about 10.0, about 6.05, and about 4.97.

13. The citrate salt of claim 2, wherein the salt is of formula IV:

14. The edisylate salt of claim 4, wherein the salt is of formula XI:

15. The citrate salt of claim 2, wherein the salt has a water solubility of about 14 mg/mL.

16. The edisylate salt of claim 4, wherein the salt has a water solubility of about 4 mg/mL.

6. A crystalline salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′

-(4-(2-methylpropyloxy)phenylmethyl)carbamide of formula I,