POLYMORPHIC FORMS OF 1-'4-(5-CYANOINDOL-3-YL)BUTYL-4-(2-CARBAMOYLBENZOFURAN-5-YL)PIPERAZINE HYDROCHLORIDE

• US 20110294825A1
• Filed: 05/04/2011
• Published: 12/01/2011
• Est. Priority Date: 06/19/2001
• Status: Active Grant

• Current Assignee: Merck Patentgesellschaft
• Original Assignee: Merck Patentgesellschaft
• Inventors: Neuenfeld, Steffen, Böttcher, Henning, Bathe, Andreas, Kniel, Heike, Helfert, Bernd, Rudolph, Susanne, Bartels, Matthias
• Granted Patent: US 8,236,804 B2
• Time in Patent Office: Days
• US Class Current: 514/254.09
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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 15/10 for impotence
• 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 25/04 Centrally acting analgesics, e.g. opioids
• 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 25/30 for treating abuse or dependence
• 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 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• 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 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings

Abstract

The invention relates to new crystalline modifications of the hydrochloride of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine, crystalline modification of the dihydrochloride of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine and amorphous 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride which are suitable in particular for the preparation of solid medicaments for the treatment or prevention of depressive disorders, anxiety disorders, bipolar disorders, mania, dementia, substance-related disorders, sexual dysfunctions, eating disorders, obesity, fibromyalgia, sleeping disorders, psychiatric disorders, cerebral infarct, tension, for the therapy of side-effects in the treatment of hypogonadism, secondary amenorrhea, premenstrual syndrome and undesired puerperal lactation.

Claims

1. A method of treating a depressive disorder, the method comprising:

administering to a patient in need thereof an effective amount of a compound which is a crystalline hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine, wherein a depressive disorder is treated in the patient.

2. The method of claim 1, wherein the depressive disorder is major depressive disorder.

3. The method of claim 2, comprising administering a pharmaceutical composition comprising the effective amount of compound and one or more conventional auxiliary substances and/or carriers.

4. The method of claim 3, wherein the compound is an anhydrate of the hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine.

5. The method of claim 3, wherein the compound is a hydrate of the hydrochloride salt of 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine.

6. The method of claim 5, wherein the hydrate is a monohydrate.

7. The method of claim 5, wherein the hydrate is a hemihydrate.

8. The method of claim 3, wherein, the compound is selected from:

1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride anhydrate in crystalline modification IV (Form III);

1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride anhydrate in crystalline modification IV (Form IV);

1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride monohydrate in crystalline modification V (Form V);

1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride hemihydrate in crystalline modification VIII (Form VIII); and

a combination thereof.

9. The method of claim 8, wherein the composition comprises Form IV.

10. The method of claim 8, wherein the composition comprises Form IV and Form V.

11. The method of claim 10, wherein the composition comprises Form IV and Form V in a molar ratio of 100 to 1 to 10 to 1.

12. The method of claim 8, wherein the composition comprises Form V.

13. The method of claim 8, wherein the composition comprises Form VIII.

14. The method of claim 8, wherein the compositions comprises Form III.

15. The method of claim 8, wherein the compound consists essentially of Form IV and Form V.

16. The method of claim 15, wherein the compound consists essentially of Form IV and Form V in a molar ratio of 100 to 1 to 10 to 1.

17. The method of claim 1, wherein the composition comprises Form IV.

18. The method of claim 1, wherein the composition comprises Form IV and Form V.

19. The method of claim 18, wherein the composition comprises Form IV and Form V in a molar ratio of 100 to 1 to 10 to 1.

20. The method of claim 1, wherein the composition comprises Form V.

21. The method of claim 1, wherein the composition comprises Form VIII.

22. The method of claim 1, wherein the compositions comprises Form III.

23. The method of claim 1, wherein the compound consists essentially of Form IV and Form V.

24. The method of claim 23, wherein the compound consists essentially of Form IV and Form V in a molar ratio of 100 to 1 to 10 to 1.