Polymorphic forms of 1-′4-(5-cyanoindol-3-yl)butyl-4-(2-carbamoylbenzofuran-5-yl)piperazine hydrochloride

• US 8,236,804 B2
• Filed: 05/04/2011
• Issued: 08/07/2012
• Est. Priority Date: 06/19/2001
• Status: Expired due to Term

• Current Assignee: Merck Patentgesellschaft
• Original Assignee: Merck Patentgesellschaft
• Inventors: Bathe, Andreas, Helfert, Bernd, Neuenfeld, Steffen, Kniel, Heike, Bartels, Matthias, Rudolph, Susanne, Böttcher, Henning
• Primary Examiner(s): CHUNG, SUSANNAH LEE
• Application Number:
  US13/100,948
• Publication Number:
  US 20110294825A1
• Time in Patent Office: 461 Days
• Field of Search: 514/254, 544/366, 544/370
• US Class Current: 514/252.1
• 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 major depressive disorder, the method comprising:

administering to a patient in need thereof a pharmaceutical composition comprising an effective amount of a compound which is 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine hydrochloride anhydrate in crystalline modification IV (Form IV) having at least five characteristic peaks selected from the degrees two-theta values corresponding to 9.08±

0.1, 12.85±

0.1, 14.50±

0.1, 16.89±

0.1, 18.89±

0.1, 20.43±

0.1, 21.72±

0.1, 24.61±

0.1, 27.35±

0.1 and 28.18±

0.1 and one or more conventional auxiliary substances and/or carriers, wherein the major depressive disorder is treated in the patient.

2. The method of claim 1, wherein the compound has at least five characteristic peaks selected from the degrees two-theta values corresponding to 12.85±

0.1, 14.50±

0.1, 20.43±

0.1, 21.72±

0.1, 27.35±

0.1 and 28.18±

0.1.

3. The method of claim 1, wherein the compound has characteristic peaks at the degrees two-theta values corresponding to 9.08±

0.1, 14.50±

0.1, 18.89±

0.1, 20.43±

0.1 and 24.61±

0.1.

4. The method of claim 1, wherein, the compound has a solubility in water of about 0.33 μ

g/mL.