WO2015040573A1 - Solvate mirabegron diméthyl-sulfoxyde et son utilisation pour le traitement de l'hyperactivité vésicale - Google Patents

Solvate mirabegron diméthyl-sulfoxyde et son utilisation pour le traitement de l'hyperactivité vésicale Download PDF

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Publication number
WO2015040573A1
WO2015040573A1 PCT/IB2014/064642 IB2014064642W WO2015040573A1 WO 2015040573 A1 WO2015040573 A1 WO 2015040573A1 IB 2014064642 W IB2014064642 W IB 2014064642W WO 2015040573 A1 WO2015040573 A1 WO 2015040573A1
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WO
WIPO (PCT)
Prior art keywords
mirabegron
formula
dimethyl sulphoxide
sulphoxide solvate
solvate
Prior art date
Application number
PCT/IB2014/064642
Other languages
English (en)
Inventor
Poonam KAUSHIK
Israr ALI
Ram Thaimattam
Mohan Prasad
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2015040573A1 publication Critical patent/WO2015040573A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/40—Unsubstituted amino or imino radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention provides mirabegron dimethyl sulphoxide, processes for its preparation, a pharmaceutical composition comprising it, and its use for the treatment of overactive bladder.
  • the present invention also provides processes for the preparation of mirabegron using mirabegron dimethyl sulphoxide solvate.
  • Mirabegron is a beta-3 adrenergic agonist disclosed in U.S. Patent No. 6,346,532. It is chemically designated as 2-(2-aminothiazol-4-yl)-N-[4-[2- ⁇ [(2R)-2-hydroxy-2- phenylethyl]amino ⁇ ethyl)phenyl]acetamide, and has the structure depicted by Formula I.
  • Mirabegron is marketed in the United States under the brand name Myrbetriq ® for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and urinary frequency.
  • the present invention provides mirabegron dimethyl sulphoxide solvate, processes for its preparation, a pharmaceutical composition comprising it, and its use for the treatment of overactive bladder.
  • the mirabegron dimethyl sulphoxide solvate of the present invention is stable, easily reproducible, and is suitable for the preparation of pharmaceutical compositions.
  • the present invention also provides processes for the preparation of mirabegron by desolvation of the mirabegron dimethyl sulphoxide solvate.
  • a first aspect of the present invention provides the mirabegron dimethyl sulphoxide solvate of Formula II:
  • a second aspect of the present invention provides a process for the preparation of the mirabegron dimethyl sulphoxide solvate of Formula II:
  • a third aspect of the present invention provides a process for the preparation of mirabegron of Formula I:
  • a fourth aspect of the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising the mirabegron dimethyl sulphoxide solvate of Formula II and one or more pharmaceutically acceptable carriers, diluents, or excipients.
  • a fifth aspect of the present invention provides the use of the mirabegron dimethyl sulphoxide solvate of Formula II for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and urinary frequency.
  • Figure 1 X-ray Powder Diffraction (XRPD) pattern of the mirabegron dimethyl sulphoxide solvate of Formula II.
  • FIG. 1 Differential Scanning Calorimetry (DSC) thermogram of the mirabegron dimethyl sulphoxide solvate of Formula II.
  • FIG. 3 Thermogravimetric Analysis (TGA) of the mirabegron dimethyl sulphoxide solvate of Formula II.
  • contacting includes dissolving, slurrying, stirring, or combinations thereof.
  • Mirabegron dimethyl sulphoxide solvate of Formula II is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 17.25 (d-spacing at 5.14 A), 17.92 (4.95 A), 19.97 (4.45 A), 20.58 (4.32 A), and 26.28 (3.39 A) ⁇ 0.2 degrees 2 ⁇ . It may be further characterized by an XRPD pattern having peaks at 3.73 (23.71 A), 9.94 (8.90 A), 21.42 (4.15 A), 21.85 (4.07 A), and 22.94 (3.88 A) ⁇ 0.2 degrees 2 ⁇ . Table 1 summarizes the d-spacing values in A, and the corresponding 2 ⁇ values in degrees 2 ⁇ , of the mirabegron dimethyl sulphoxide solvate of Formula II.
  • XRPD X-ray powder diffraction
  • the mirabegron dimethyl sulphoxide solvate of Formula II may also be characterized by a DSC thermogram having endotherms at about 91.50°C and about 93.68°C.
  • the mirabegron dimethyl sulphoxide solvate of Formula II may also be characterized by an XRPD pattern, a DSC thermogram, and a TGA as depicted in Figures 1-3, respectively.
  • Mirabegron used for the preparation of the mirabegron dimethyl sulphoxide solvate of Formula II may be obtained by the methods known in the literature, such as those described in U.S. Patent No. 7,342,117 and PCT Publication No. WO 2012/156998 which are incorporated herein by reference.
  • the preparation of the mirabegron dimethyl sulphoxide solvate of Formula II is carried out by contacting mirabegron of Formula I with dimethyl sulphoxide at a temperature of about 20°C to the reflux temperature of the solvent.
  • the preparation of the mirabegron dimethyl sulphoxide solvate of Formula II may also be carried out using a solvent selected from the group comprising of aromatic hydrocarbons, alkyl acetates, and mixtures thereof. Examples of aromatic hydrocarbons include toluene and xylene.
  • alkyl acetates examples include ethyl acetate, propyl acetate, isopropyl acetate, and t- butyl acetate.
  • the preparation of the mirabegron dimethyl sulphoxide solvate of Formula II may also be carried out by stirring the reaction mixture at a temperature of about 20°C to about 40°C for about 15 minutes to about 4 hours.
  • Isolation of the mirabegron dimethyl sulphoxide solvate of Formula II may be accomplished by crystallization, concentration, precipitation, cooling, filtration, centrifugation, or a combination thereof, followed by drying. Any suitable method of drying may be employed such as drying under reduced pressure, vacuum tray drying, air drying, or a combination thereof. Drying is carried out at a temperature of about 20°C to about 40°C for about 30 minutes to about 20 hours.
  • the mirabegron dimethyl sulphoxide solvate of Formula II is prepared by dissolving mirabegron in a mixture of dimethyl sulphoxide and an aromatic hydrocarbon solvent, stirring the reaction mixture for about 15 minutes to about 2 hours at a temperature of about 20°C to about 40°C, followed by isolation.
  • the mirabegron dimethyl sulphoxide solvate of Formula II is prepared by dissolving mirabegron in a mixture of dimethyl sulphoxide and an alkyl acetate solvent, stirring the reaction mixture for about 15 minutes to about 2 hours at a temperature of about 20°C to about 40°C, followed by isolation.
  • the mirabegron dimethyl sulphoxide solvate of Formula II is prepared by using a mixture of dimethyl sulphoxide with toluene, or a mixture of dimethyl sulphoxide with i-butyl acetate as a solvent.
  • the desolvation of the mirabegron dimethyl sulphoxide solvate is carried out by stirring a reaction mixture containing the mirabegron dimethyl sulphoxide solvate in a solvent selected from the group comprising of water, chlorinated hydrocarbons, alcohols, ketones, and mixtures thereof at a temperature of about 0°C to about 50°C.
  • chlorinated hydrocarbons include dichloromethane and chloroform.
  • Examples of alcohols include methanol, ethanol, iso-propanol, and butanol.
  • ketones include acetone, dimethyl ketone, ethyl methyl ketone, and methyl iso-butyl ketone.
  • the desolvation of the mirabegron dimethyl sulphoxide solvate of Formula II is carried out by contacting the mirabegron dimethyl sulphoxide solvate of Formula II with water at a temperature of about 25 °C to about 35°C.
  • the reaction mixture is stirred for about 30 minutes to about 2 hours, filtered, and the solid obtained is dried at a temperature of about 40°C to about 50°C under vacuum.
  • the desolvation of the mirabegron dimethyl sulphoxide solvate of Formula II is carried out by contacting the mirabegron dimethyl sulphoxide solvate of Formula II with acetone at a temperature of about 0°C to about 10°C.
  • the reaction mixture is stirred for about 30 minutes to about 2 hours, filtered, and the solid obtained is dried at a temperature of about 20°C to about 40°C under vacuum.
  • Mirabegron dimethyl sulphoxide solvate of Formula II may be administered as part of a pharmaceutical composition for the treatment of overactive bladder. Accordingly, in a further aspect, there is provided a pharmaceutical composition comprising mirabegron dimethyl sulphoxide solvate of Formula II, one or more pharmaceutically acceptable carriers, diluents, or excipients, and optionally other therapeutic ingredients.
  • compositions comprising mirabegron dimethyl sulphoxide solvate of Formula II may be administered orally, topically, parenterally, by inhalation or spray, rectally, or in the form of injectables.
  • the injectable compositions may include intravenous, intramuscular, subcutaneous, and parenteral injections, as well as use of infusion techniques.
  • the X-ray powder diffraction (XRPD) pattern was recorded using a PANalytical ® X'pert PRO with X'celerator ® as the detector.
  • the DSC was recorded using a Mettler-Toledo ® 82 le. Data collection parameters: Scanning rate: 10°C/minute; Temperature: 30°C to 300°C.
  • the TGA was recorded using a TA Instruments ® Q500.
  • Mirabegron (1.5 g) was suspended in a mixture of dimethyl sulphoxide (1.0 mL) and toluene (2 mL). The reaction mixture was stirred for about 30 minutes at a temperature of about 25°C to about 35°C. The reaction mixture was diluted with toluene (5 mL). The solid obtained was filtered, washed with toluene (40 mL), and dried in a vacuum tray dryer at a temperature of about 25°C to about 35°C for about 16 hours to obtain the mirabegron dimethyl sulphoxide solvate.
  • Mirabegron (4.5 g) was suspended in a mixture of dimethyl sulphoxide (3 mL) and /-butyl acetate (45 mL). The reaction mixture was stirred at a temperature of about 25 °C to about 35°C for about 3 hours. The solid obtained was filtered, washed with i-butyl acetate (30 mL), and dried in a vacuum tray dryer at a temperature of about 25 °C to about 35°C for about 3 hours to obtain the mirabegron dimethyl sulphoxide solvate.
  • Example 2 Preparation of mirabegron by desolvation of the mirabegron dimethyl sulphoxide solvate

Abstract

La présente invention porte sur le mirabegron, diméthyl-sulfoxyde, sur des procédés pour le préparer, sur une composition pharmaceutique le contenant, et sur son utilisation pour le traitement de l'hyperactivité vésicale. La présente invention concerne également des procédés de préparation de mirabegron à partir de solvate mirabegron diméthyl-sulfoxyde.
PCT/IB2014/064642 2013-09-23 2014-09-18 Solvate mirabegron diméthyl-sulfoxyde et son utilisation pour le traitement de l'hyperactivité vésicale WO2015040573A1 (fr)

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IN2800/DEL/2013 2013-09-23
IN2800DE2013 2013-09-23

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016049749A1 (fr) * 2014-10-01 2016-04-07 Apotex Inc. Formes solides du mirabégron

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6346532B1 (en) 1997-10-17 2002-02-12 Yamanouchi Pharmaceutical Co., Ltd. Amide derivatives or salts thereof
EP1440969A1 (fr) * 2001-10-30 2004-07-28 Yamanouchi Pharmaceutical Co. Ltd. Cristal a forme alpha ou beta d'un derive acetanilinide
WO2010147830A2 (fr) * 2009-06-15 2010-12-23 Auspex Pharmaceuticals, Inc. Modulateurs aminothiazole de bêta-3-adrénorécepteur
WO2012156998A2 (fr) 2011-05-18 2012-11-22 Dr. Reddy's Laboratories Limited Mirabegron amorphe et procédés de préparation de formes cristallines de mirabegron

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6346532B1 (en) 1997-10-17 2002-02-12 Yamanouchi Pharmaceutical Co., Ltd. Amide derivatives or salts thereof
EP1440969A1 (fr) * 2001-10-30 2004-07-28 Yamanouchi Pharmaceutical Co. Ltd. Cristal a forme alpha ou beta d'un derive acetanilinide
US7342117B2 (en) 2001-10-30 2008-03-11 Astellas Pharma Inc. α-form or β-form crystal of acetanilide derivative
WO2010147830A2 (fr) * 2009-06-15 2010-12-23 Auspex Pharmaceuticals, Inc. Modulateurs aminothiazole de bêta-3-adrénorécepteur
WO2012156998A2 (fr) 2011-05-18 2012-11-22 Dr. Reddy's Laboratories Limited Mirabegron amorphe et procédés de préparation de formes cristallines de mirabegron

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A S MCKIM ET AL: "Dimethyl Sulfoxide USP, PhEur in Approved Pharmaceutical Products and Medical Devices Dimethyl sulfoxide USP in dosage forms and devices", 1 January 2007 (2007-01-01), XP055146360, Retrieved from the Internet <URL:http://www.gaylordchemical.com/uploads/images/pdfs/literature/166.pdf> [retrieved on 20141014] *
JULIEN DOUILLET ET AL: "Development of a solvate as an active pharmaceutical ingredient: Developability, crystallisation and isolation challenges", JOURNAL OF CRYSTAL GROWTH, vol. 342, no. 1, 1 March 2012 (2012-03-01), pages 2 - 8, XP055068245, ISSN: 0022-0248, DOI: 10.1016/j.jcrysgro.2011.05.023 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016049749A1 (fr) * 2014-10-01 2016-04-07 Apotex Inc. Formes solides du mirabégron

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