WO2016063246A1 - Forme cristalline r de phosphate de tédizolide - Google Patents

Forme cristalline r de phosphate de tédizolide Download PDF

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Publication number
WO2016063246A1
WO2016063246A1 PCT/IB2015/058159 IB2015058159W WO2016063246A1 WO 2016063246 A1 WO2016063246 A1 WO 2016063246A1 IB 2015058159 W IB2015058159 W IB 2015058159W WO 2016063246 A1 WO2016063246 A1 WO 2016063246A1
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WO
WIPO (PCT)
Prior art keywords
tedizolid phosphate
crystalline form
acetate
solution
tedizolid
Prior art date
Application number
PCT/IB2015/058159
Other languages
English (en)
Inventor
Anu Arya
Ram Thaimattam
Mohan Prasad
Original Assignee
Sun Pharmaceutical Industries 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 Sun Pharmaceutical Industries Limited filed Critical Sun Pharmaceutical Industries Limited
Publication of WO2016063246A1 publication Critical patent/WO2016063246A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole

Definitions

  • the present invention provides a crystalline form R of tedizolid phosphate, a process for its preparation, a pharmaceutical composition comprising it, and its use for the treatment of bacterial infections.
  • Tedizolid phosphate chemically is [(5i?)-3- ⁇ 3-fluoro-4-[6-(2-methyl-2H-tetrazol-5- yl)pyridin-3-yl]phenyl ⁇ -2-oxooxazolidin-5-yl]methyl hydrogen phosphate, represented by Formula I.
  • Tedizolid phosphate is indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria.
  • U.S. Patent No. 8,426,389 discloses a crystalline form of tedizolid phosphate.
  • the present invention provides a crystalline form R of tedizolid phosphate, a process for its preparation, a pharmaceutical composition comprising it, and its use for the treatment of bacterial infections.
  • the crystalline form R of tedizolid phosphate can be formed under various crystallization conditions.
  • Figure 1 depicts an X-ray powder diffraction (XRPD) pattern of a crystalline form R of tedizolid phosphate.
  • Figure 2 depicts a Differential Scanning Calorimetry (DSC) thermogram of a crystalline form R of tedizolid phosphate.
  • DSC Differential Scanning Calorimetry
  • Figure 3 depicts an Infra-red (IR) absorption spectrum of a crystalline form R of tedizolid phosphate.
  • contacting refers to dissolving, slurrying, stirring, suspending, or combinations thereof.
  • a first aspect of the present invention provides a crystalline form R of tedizolid phosphate characterized by an X-ray powder diffraction (XRPD) pattern having peaks at d-spacings of about 5.2, 4.1, 3.9, and 3.8 A, and additional peaks at d-spacings of about 4.2, 4.0, 3.4, and 3.3 A.
  • XRPD X-ray powder diffraction
  • Table 1 provides the d-spacing values (A), the corresponding 2 ⁇ values, and the relative intensity (%) of crystalline form R of tedizolid phosphate.
  • the crystalline form R of tedizolid phosphate is further characterized by a differential scanning calorimetry (DSC) thermogram having endotherms at about 59.5°C and 225.0°C.
  • DSC differential scanning calorimetry
  • the crystalline form R of tedizolid phosphate is also characterized by an XRPD pattern substantially as depicted in Figure 1, a DSC thermogram substantially as depicted in Figure 2, or an IR absorption spectrum substantially as depicted in Figure 3.
  • a second aspect of the present invention provides a process for the preparation of a crystalline form R of tedizolid phosphate, comprising:
  • step a) adding a solvent selected from the group consisting of ketones, esters, nitriles, ethers, and mixtures thereof to the solution of step a) to obtain the crystalline form R of tedizolid phosphate.
  • Tedizolid phosphate used for the preparation of crystalline form R of tedizolid phosphate may be prepared according to the methods provided in the art, for example, U.S. Patent Nos. 7,816,379 or 8,604,209.
  • Tedizolid phosphate is contacted with orthophosphoric acid at a temperature of about 50°C to about 70°C, for example, of about 55°C to about 65°C.
  • ketones include acetone, butan-2-one, and isobutyl methyl ketone.
  • esters include methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, isobutyl acetate, n-butyl acetate, and tert-butyl acetate.
  • ethers include diethyl ether, ethyl methyl ether, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, and 1,4-dioxane.
  • nitrile is acetonitrile.
  • the preparation of the crystalline form R of tedizolid phosphate is carried out at a temperature of about 40°C to about 80°C, for example, of about 45°C to about 70°C.
  • the preparation of the crystalline form R of tedizolid phosphate is carried out for about 1 hour to about 12 hours, for example, for about 2 hours to about 9 hours.
  • the crystalline form R of tedizolid phosphate may be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization, and dried under reduced pressure, by air drying or vacuum tray drying.
  • a third aspect of the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a crystalline form R of tedizolid phosphate and one or more pharmaceutically acceptable carriers, diluents, or excipients.
  • a fourth aspect of the present invention provides a method of treating bacterial infections comprising administering to a patient in need thereof a therapeutically effective amount of a crystalline form R of tedizolid phosphate.
  • the X-ray powder diffraction (XRPD) pattern was recorded using a PANalytical® X'pert PRO with X'celerator® as the detector.
  • the DSC thermogram was recorded on a Mettler-Toledo® 82 le.
  • the IR spectrum was recorded using a Perkin Elmer® instrument.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Isobutyl methyl ketone (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 6 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Methyl tert-butyl ether (25 mL) was added to the solution. The resulting mixture was stirred at 50°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 6 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.5 mL) at 60°C to obtain a solution. Acetonitrile (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 5.5 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Acetonitrile (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 6 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Acetone (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 6 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Ethyl acetate (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 7 hours to obtain the title compound. Yield: 0.30 g
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Methyl acetate (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 7 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution. Isopropyl acetate (25 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 7 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at 60°C to obtain a solution.
  • n-Butyl acetate 25 mL was added to the solution.
  • the resulting mixture was stirred at 60°C for 8 hours to obtain a precipitate.
  • the precipitate was filtered, then dried under vacuum at 50°C for 7 hours to obtain the title compound. Yield: 0.27 g
  • Tedizolid phosphate (0.50 g) was dissolved in orthophosphoric acid (1.5 mL) at 60°C to obtain a solution. Acetonitrile (35 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at room temperature for 15 hours to obtain the title compound.
  • Tedizolid phosphate (0.30 g) was dissolved in orthophosphoric acid (1.0 mL) at
  • Tedizolid phosphate (5.0 g) was dissolved in orthophosphoric acid (13.0 mL) at 60°C to obtain a solution. Acetonitrile (250 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 60°C for 9 hours to obtain the title compound.
  • Tedizolid phosphate (5.0 g) was dissolved in orthophosphoric acid (13.0 mL) at 60°C to obtain a solution. Isobutyl methyl ketone (250 mL) was added to the solution. The resulting mixture was stirred at 60°C for 4 hours to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 60°C for 14 hours to obtain the title compound.
  • Tedizolid phosphate (0.5 g) was dissolved in orthophosphoric acid (2.0 mL) at 60°C to obtain a solution. Acetonitrile (40 mL) was added to the solution. The resulting mixture was stirred at 60°C for 3 hours. The reaction mixture was cooled at 25°C to 30°C to obtain a precipitate. The precipitate was filtered, then dried under vacuum at 50°C for 9 hours to obtain the title compound.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une forme cristalline R de phosphate de tédizolide, un procédé pour sa préparation, une composition pharmaceutique le comprenant, et son utilisation pour le traitement d'infections bactériennes.
PCT/IB2015/058159 2014-10-22 2015-10-22 Forme cristalline r de phosphate de tédizolide WO2016063246A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3027DE2014 2014-10-22
IN3027/DEL/2014 2014-10-22

Publications (1)

Publication Number Publication Date
WO2016063246A1 true WO2016063246A1 (fr) 2016-04-28

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3464985A (en) * 1967-08-18 1969-09-02 Bristol Myers Co 7 - (d - alpha - amino - (acetamidophenylacetamido))-cephalosporanic acids and derivatives thereof
US20050020488A1 (en) * 2001-08-24 2005-01-27 Leadbetter Michael R. Process for preparing glycopeptide phosphonate derivatives
US20100305069A1 (en) * 2009-05-28 2010-12-02 Trius Therapeutics Oxazolidinone containing dimer compounds, compositions and methods to make and use
WO2013093693A1 (fr) * 2011-12-22 2013-06-27 Rinat Neuroscience Corp. Anticorps spécifiques de staphylococcus aureus et leurs utilisations
US20130310343A1 (en) * 2009-02-03 2013-11-21 Trius Therapeutics, Inc. Crystalline form of r)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin- 5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3464985A (en) * 1967-08-18 1969-09-02 Bristol Myers Co 7 - (d - alpha - amino - (acetamidophenylacetamido))-cephalosporanic acids and derivatives thereof
US20050020488A1 (en) * 2001-08-24 2005-01-27 Leadbetter Michael R. Process for preparing glycopeptide phosphonate derivatives
US20130310343A1 (en) * 2009-02-03 2013-11-21 Trius Therapeutics, Inc. Crystalline form of r)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin- 5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate
US20100305069A1 (en) * 2009-05-28 2010-12-02 Trius Therapeutics Oxazolidinone containing dimer compounds, compositions and methods to make and use
WO2013093693A1 (fr) * 2011-12-22 2013-06-27 Rinat Neuroscience Corp. Anticorps spécifiques de staphylococcus aureus et leurs utilisations

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