WO2009085972A1 - Sels de maléate, de bésylate et de l-malate de 6-(5-chloro-2-pyridyl)-5-[(4-méthyl-1-pipérazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]-pyrazine - Google Patents

Sels de maléate, de bésylate et de l-malate de 6-(5-chloro-2-pyridyl)-5-[(4-méthyl-1-pipérazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]-pyrazine Download PDF

Info

Publication number
WO2009085972A1
WO2009085972A1 PCT/US2008/087461 US2008087461W WO2009085972A1 WO 2009085972 A1 WO2009085972 A1 WO 2009085972A1 US 2008087461 W US2008087461 W US 2008087461W WO 2009085972 A1 WO2009085972 A1 WO 2009085972A1
Authority
WO
WIPO (PCT)
Prior art keywords
salt
besylate
maleate
eszopiclone
zopiclone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2008/087461
Other languages
English (en)
Inventor
H. Scott Wilkinson
Richard Hsia
Tushar Misra
Kostas Saranteas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sumitomo Pharma America Inc
Original Assignee
Sepracor Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sepracor Inc filed Critical Sepracor Inc
Priority to CA2747000A priority Critical patent/CA2747000C/fr
Publication of WO2009085972A1 publication Critical patent/WO2009085972A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics

Definitions

  • treating or preventing an affective disorder means reducing the severity of at least one symptom associated with a psychological disorder characterized by abnormality of emotional state, including but not limited to, depression, dysthymia, attention deficit disorder, attention deficit disorder with hyperactivity, bipolar disorders, bipolar and manic conditions, and the like.
  • ADD attention deficit disorder
  • ADHD attention deficit/hyperactivity disorder
  • Another embodiment of the invention encompasses a method of treating alcohol or drug addiction in a subject which comprises administering to a subject in need of such treatment a therapeutically or prophylactically effective amount of a zopiclone maleate, besylate or L-malate salt.
  • treating alcohol or drug addiction means reducing at least one symptom of disease or conditions related to alcohol or drug addiction including, but not limited to, drug or alcohol addiction or symptoms of withdrawal from alcohol or drugs.
  • fillers suitable for use in the pharmaceutical compositions and dosage forms disclosed herein include, but are not limited to, talc, calcium carbonate (e.g., granules or powder), microcrystalline cellulose, powdered cellulose, dextrates, kaolin, mannitol, silicic acid, sorbitol, starch, pre-gelatinized starch, and mixtures thereof.
  • the binder or filler in pharmaceutical compositions of the invention is typically present in from about 50 to about 99 weight percent of the pharmaceutical composition or dosage form.
  • Additional lubricants include, for example, a syloid silica gel (AEROSIL 200, manufactured by W.R. Grace Co. of Baltimore, Md.), a coagulated aerosol of synthetic silica (marketed by Degussa Co. of Piano, Tex.), CAB-O-SIL (a pyrogenic silicon dioxide product sold by Cabot Co. of Boston, Mass.), and mixtures thereof. If used at all, lubricants are typically used in an amount of less than about 1 weight percent of the pharmaceutical compositions or dosage forms into which they are incorporated.
  • AEROSIL 200 a syloid silica gel
  • a coagulated aerosol of synthetic silica marketed by Degussa Co. of Piano, Tex.
  • CAB-O-SIL a pyrogenic silicon dioxide product sold by Cabot Co. of Boston, Mass.
  • Transdermal, topical, and mucosal dosage forms of the invention include, but are not limited to, ophthalmic solutions, sprays, aerosols, creams, lotions, ointments, gels, solutions, emulsions, suspensions, or other forms known to one of skill in the art. See, e.g., Remington's Pharmaceutical Sciences, 16th and 18th eds., Mack Publishing, Easton Pa. (1980 & 1990); and Introduction to Pharmaceutical Dosage Forms, 4th ed., Lea & Febiger, Philadelphia (1985). Dosage forms suitable for treating mucosal tissues within the oral cavity can be formulated as mouthwashes or as oral gels. Further, transdermal dosage forms include "reservoir type" or "matrix type” patches, which can be applied to the skin and worn for a specific period of time to permit the penetration of a desired amount of active ingredients.
  • excipients include, but are not limited to, water, acetone, ethanol, ethylene glycol, propylene glycol, butane- 1,3-diol, isopropyl myristate, isopropyl palmitate, mineral oil, and mixtures thereof to form lotions, tinctures, creams, emulsions, gels or ointments, which are non-toxic and pharmaceutically acceptable.
  • Moisturizers or humectants can also be added to pharmaceutical compositions and dosage forms if desired. Examples of such additional ingredients are well known in the art. See, e.g., Remington's Pharmaceutical Sciences, 16th and 18th eds., Mack Publishing, Easton Pa. (1980 & 1990).
  • penetration enhancers can be used to assist in delivering the active ingredients to the tissue.
  • Suitable penetration enhancers include, but are not limited to: acetone; various alcohols such as ethanol, oleyl, and tetrahydrofuryl; alkyl sulfoxides such as dimethyl sulfoxide; dimethyl acetamide; dimethyl formamide; polyethylene glycol; pyrrolidones such as polyvinylpyrrolidone; Kollidon grades (Povidone, Polyvidone); urea; and various water-soluble or insoluble sugar esters such as Tween 80 (polysorbate 80) and Span 60 (sorbitan monostearate).
  • the maleate, besylate or L-malate salt of zopiclone can, for example, be administered with a dosage ranging from about 0.001 to about 0.2 mg/kg of body weight, alternatively dosages between 0.1 mg and 15 mg/dose, or between about 0.1 mg and about 10 mg/dose, or preferably between about 0.2 mg and about 5 mg/dose, or according to the requirements of the particular therapy.
  • the methods herein contemplate administration of an effective amount of compound or compound composition to achieve the desired or stated effect.
  • the pharmaceutical compositions of this invention will be administered from about 1 to about 6 times per day or alternatively, as a continuous infusion. Such administration can be used as a chronic or acute therapy.
  • the amounts and specific types of active ingredients in a dosage form can differ depending on factors such as, but not limited to, the route by which it is to be administered to patients.
  • the doses depend on the effect sought and the treatment period; taken orally, they are generally between 0.5 and 15 mg per day for an adult.
  • unit dosages containing 0.5 mg, 1 mg, 2 mg or 3 mg of a present eszopiclone salt will be suitable.
  • the unit dosages of the eszopiclone salts can be adjusted to contain the molar equivalent of 0.5 mg, 1 mg, 2 mg or 3 mg of eszopiclone freebase.
  • the ⁇ Astree II Bitterness Prediction Module (BPM) and Electronic Tongue (E- Tongue) was utilized to perform taste assessments.
  • the sensory (E-tongue) apparatus utilized is commercially available (Alpha-mos, Hillsborough, New Jersey) and includes three arrays of seven sensors with the third array utilized to assess bitterness of chemical identities.
  • the bitterness results were obtained with the ⁇ Astree II BPM used in a pharmaceutical configuration for bitterness assessment of eszopiclone, and its salts prepared at various concentrations using the third sensor array.
  • Dissolution over time of eszopiclone salts was compared to that of free base at room temperature in pH 4.5 2OmM acetate buffer using Hanson Research SR8-Plus Dissolution Apparatus and C-Technologies Fiber Optic Probes.
  • a standard dissolution protocol was used. For example, 100.12 mg eszopiclone free base (MW 388.81; purity 99.9%) or 129.98 mg L-malate (MW 504.88; purity 99.8%) or 140.93 mg besylate (MW 546.99; purity 99.8%) or 129.98 mg maleate (MW 504.88; purity 99.9%) was added to an empty vessel.
  • the Flavor Profile is an art-recognized descriptive sensory analysis method used to measure the type and intensity of attributes in products and ingredients, [see Keane, P. The Flavor Profile Method. In C. Hootman (Ed.), Manual on Descriptive Analysis Testing for Sensory Evaluation ASTM Manual Series: MNL 13. Baltimore, MD. (1992).] It is based on the concept that flavor consists of identifiable taste, odor (aroma), and chemical feeling attributes, plus an underlying complex of attributes not separately identifiable. The method consists of formal procedures for describing and assessing the flavor of a product in a reproducible manner.
  • the flavor profile panel consisted of four persons who have normal ability to smell and taste, have been trained in fundamental sensory principles and all aspects of the Flavor Profile technique and have considerable experience as panel members.
  • the samples to be profiled were uniform and representative. Sample preparation and presentation were standardized and controlled. Each panel member received an aliquot for his/her own independent analysis.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Anesthesiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne de nouveaux sels de maléate, de bésylate et de L-malate de 6-(5-chloro-2-pyridyl)-5-[(4-méthyl-1-pipérazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-B]-pyrazine.
PCT/US2008/087461 2007-12-19 2008-12-18 Sels de maléate, de bésylate et de l-malate de 6-(5-chloro-2-pyridyl)-5-[(4-méthyl-1-pipérazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]-pyrazine Ceased WO2009085972A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2747000A CA2747000C (fr) 2007-12-19 2008-12-18 Sels de maleate, de besylate et de l-malate de 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]-pyrazine

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US836507P 2007-12-19 2007-12-19
US836307P 2007-12-19 2007-12-19
US836407P 2007-12-19 2007-12-19
US61/008,364 2007-12-19
US61/008,365 2007-12-19
US61/008,363 2007-12-19

Publications (1)

Publication Number Publication Date
WO2009085972A1 true WO2009085972A1 (fr) 2009-07-09

Family

ID=40404919

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/087461 Ceased WO2009085972A1 (fr) 2007-12-19 2008-12-18 Sels de maléate, de bésylate et de l-malate de 6-(5-chloro-2-pyridyl)-5-[(4-méthyl-1-pipérazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]-pyrazine

Country Status (4)

Country Link
AR (1) AR069867A1 (fr)
CA (2) CA2747000C (fr)
TW (1) TW200940543A (fr)
WO (1) WO2009085972A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8198278B2 (en) 2007-12-19 2012-06-12 Sunovion Pharmaceuticals Inc. Besylate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8198277B2 (en) 2007-12-19 2012-06-12 Sunovion Pharmaceuticals Inc. L-malate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8212036B2 (en) 2007-12-19 2012-07-03 Sunovion Pharmaceuticals Inc. Maleate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8268832B2 (en) 2007-12-19 2012-09-18 Sunovion Pharmaceuticals Inc. Maleate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8269005B2 (en) 2007-12-19 2012-09-18 Sunovion Pharmaceuticals Inc. L-malate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-Oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US11091439B2 (en) 2009-01-16 2021-08-17 Exelixis, Inc. Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3862149A (en) * 1972-01-07 1975-01-21 Rhone Poulenc Sa Pyrrolo (3,4-b) pyrazine derivatives
WO1993010787A1 (fr) * 1991-12-02 1993-06-10 Sepracor, Inc. Procedes et compositions therapeutiques de troubles du sommeil, d'attaques epileptiques et d'autres troubles au moyen de zopiclone (+) optiquement pure
US5786357A (en) * 1991-12-02 1998-07-28 Sepracor Inc. Methods and compositions for treating sleep disorders, convulsive seizures and other disorders using optically pure (+) zopiclone
US6319926B1 (en) * 1991-01-17 2001-11-20 Sepracor Inc. Optically active 5H-pyrrolo[3, 4-B]pyrazine derivative, its preparation and pharmaceutical compositions containing it
WO2005060968A1 (fr) * 2003-12-11 2005-07-07 Sepracor Inc. Combinaison d'un sedatif et d'un modulateur des neurotransmetteurs, et methodes permettant d'ameliorer la qualite du sommeil et de traiter la depression
WO2005063248A1 (fr) * 2003-12-22 2005-07-14 Sepracor Inc. Therapie combinatoire avec la modafinile pour ameliorer la qualite du sommeil
WO2005097132A2 (fr) * 2004-04-05 2005-10-20 Sepracor Inc. Procedes de traitement utilisant l'eszopiclone
WO2007006003A2 (fr) * 2005-07-06 2007-01-11 Sepracor Inc. Combinaisons d'eszopiclone et de trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphtalenamine, et methodes de traitement de la menopause et des troubles de l'humeur, de l'anxiete et troubles cognitifs

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3862149A (en) * 1972-01-07 1975-01-21 Rhone Poulenc Sa Pyrrolo (3,4-b) pyrazine derivatives
US6319926B1 (en) * 1991-01-17 2001-11-20 Sepracor Inc. Optically active 5H-pyrrolo[3, 4-B]pyrazine derivative, its preparation and pharmaceutical compositions containing it
US6444673B1 (en) * 1991-01-17 2002-09-03 Sepracor Inc. Optically active 5H-pyrrolo[3,4-b]pyrazine derivative, its preparation and pharmaceutical compositions containing it
US6864257B2 (en) * 1991-01-17 2005-03-08 Sepracor Inc. Optically active 5H-pyrrolo[3,4-b]pyrazine derivative, its preparation and pharmaceutical compositions containing it
US7125874B2 (en) * 1991-01-17 2006-10-24 Sepracor Inc. Optically active 5H-pyrrolo[3,4-b] pyrazine derivative, its preparation and pharmaceutical compositions containing same
WO1993010787A1 (fr) * 1991-12-02 1993-06-10 Sepracor, Inc. Procedes et compositions therapeutiques de troubles du sommeil, d'attaques epileptiques et d'autres troubles au moyen de zopiclone (+) optiquement pure
US5786357A (en) * 1991-12-02 1998-07-28 Sepracor Inc. Methods and compositions for treating sleep disorders, convulsive seizures and other disorders using optically pure (+) zopiclone
WO2005060968A1 (fr) * 2003-12-11 2005-07-07 Sepracor Inc. Combinaison d'un sedatif et d'un modulateur des neurotransmetteurs, et methodes permettant d'ameliorer la qualite du sommeil et de traiter la depression
WO2005063248A1 (fr) * 2003-12-22 2005-07-14 Sepracor Inc. Therapie combinatoire avec la modafinile pour ameliorer la qualite du sommeil
WO2005097132A2 (fr) * 2004-04-05 2005-10-20 Sepracor Inc. Procedes de traitement utilisant l'eszopiclone
WO2007006003A2 (fr) * 2005-07-06 2007-01-11 Sepracor Inc. Combinaisons d'eszopiclone et de trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-naphtalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphtalenamine, et methodes de traitement de la menopause et des troubles de l'humeur, de l'anxiete et troubles cognitifs

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8198278B2 (en) 2007-12-19 2012-06-12 Sunovion Pharmaceuticals Inc. Besylate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8198277B2 (en) 2007-12-19 2012-06-12 Sunovion Pharmaceuticals Inc. L-malate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8212036B2 (en) 2007-12-19 2012-07-03 Sunovion Pharmaceuticals Inc. Maleate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8268832B2 (en) 2007-12-19 2012-09-18 Sunovion Pharmaceuticals Inc. Maleate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8269005B2 (en) 2007-12-19 2012-09-18 Sunovion Pharmaceuticals Inc. L-malate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-Oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8497268B2 (en) 2007-12-19 2013-07-30 Sunovion Pharmaceuticals Inc. Method for providing blood levels of eszopiclone with maleate salts
US8497267B2 (en) 2007-12-19 2013-07-30 Sunovion Pharmaceuticals Inc. Method for treating a sleep disorder with a dosage form of besylate salts of zopiclone or eszopiclone
US8541416B2 (en) 2007-12-19 2013-09-24 Sunovion Pharmaceuticals Inc. Method for treating a sleep disorder with a dosage form of a zopiclone or eszopiclone L-malate salt
US8809332B2 (en) 2007-12-19 2014-08-19 Sunovion Pharmaceuticals Inc. Method for treating anxiety with a dosage form of besylate salts of zopiclone or eszopiclone
US8889685B2 (en) 2007-12-19 2014-11-18 Sunovion Pharmaceuticals Inc. Method for treating a sleep disorder with eszopiclone maleate
US8889686B2 (en) 2007-12-19 2014-11-18 Sunovion Pharmaceuticals Inc. Method of decreasing the bitterness of a pharmaceutical dosage form containing zopiclone
US11091439B2 (en) 2009-01-16 2021-08-17 Exelixis, Inc. Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer
US11091440B2 (en) 2009-01-16 2021-08-17 Exelixis, Inc. Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)- N′-(4-fluorophenyl)cyclopropane-1,1 -dicarboxamide, and crystalline forms thereof for the treatment of cancer
US11098015B2 (en) 2009-01-16 2021-08-24 Exelixis, Inc. Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer
US12275706B2 (en) 2009-01-16 2025-04-15 Exelixis, Inc. Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer

Also Published As

Publication number Publication date
TW200940543A (en) 2009-10-01
CA2812705A1 (fr) 2009-07-09
CA2747000A1 (fr) 2009-07-09
CA2747000C (fr) 2013-09-03
CA2812705C (fr) 2015-08-18
AR069867A1 (es) 2010-02-24

Similar Documents

Publication Publication Date Title
US8889685B2 (en) Method for treating a sleep disorder with eszopiclone maleate
US8889686B2 (en) Method of decreasing the bitterness of a pharmaceutical dosage form containing zopiclone
US8809332B2 (en) Method for treating anxiety with a dosage form of besylate salts of zopiclone or eszopiclone
US8269005B2 (en) L-malate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-Oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
US8268832B2 (en) Maleate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine
DE60114215T2 (de) Kondensierte pyrrolocarbazole gegen entzündungen
US7456173B2 (en) Compositions comprising zopiclone derivatives and methods of making and using the same
EP2938341B1 (fr) Composés hétérocycliques et leurs procédés d'utilisation
JP2023513680A (ja) 中枢神経系障害の治療のためのセロトニン作動性幻覚薬としてのシロシン誘導体
CA2747000C (fr) Sels de maleate, de besylate et de l-malate de 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b]-pyrazine
JP2004517852A (ja) インドール誘導体および５−ｈｔ２ｂおよび５−ｈｔ２ｃ受容体リガンドとしてのそれらの使用
IE64429B1 (en) 1, 2, 3, 3a, 8, 8a-hexahydro-1, 3a, 8-trimethylpyrroloÚ2, 3-b¾ indoles, a process for their preparation and their use as medicaments
CA2747008C (fr) Sels de 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5h-pyrrolo[3,4-b] pyrazine
CN109890824B (zh) 作为pde2抑制剂的[1,2,4]三唑并[1,5-a]嘧啶化合物
EP0430201B1 (fr) Aminocarbonylcarbamates apparentés à la physostigmine, leur procédé de préparation et leur utilisation comme médicaments
CN114685449B (zh) 氟取代西洛他唑衍生物的制备和应用
EP2981538B1 (fr) Pipérazino[1,2-a]indol-1-ones et [1,4]diazépino[1,2-a]indol-1-one

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08868536

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08868536

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2747000

Country of ref document: CA