WO2016198031A1 - Sel de bédaquiline avec acide citrique - Google Patents

Sel de bédaquiline avec acide citrique Download PDF

Info

Publication number
WO2016198031A1
WO2016198031A1 PCT/CZ2016/000063 CZ2016000063W WO2016198031A1 WO 2016198031 A1 WO2016198031 A1 WO 2016198031A1 CZ 2016000063 W CZ2016000063 W CZ 2016000063W WO 2016198031 A1 WO2016198031 A1 WO 2016198031A1
Authority
WO
WIPO (PCT)
Prior art keywords
bedaquiline
citric acid
salt
citrate
alpha
Prior art date
Application number
PCT/CZ2016/000063
Other languages
English (en)
Inventor
Pavel ZVATORA
Ondrej Dammer
Lukas KREJCIK
Vit ZVONICEK
Jakub Hert
Original Assignee
Zentiva, K.S.
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 Zentiva, K.S. filed Critical Zentiva, K.S.
Publication of WO2016198031A1 publication Critical patent/WO2016198031A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/265—Citric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the invention relates to a novel solid form of (li?,2S)-l-(6-bromo-2-methoxy-3-quinolyl)-4- dimethylamino-2-(l-naphthyl)-l- henyl-butan-2-ol of formula (I),
  • bedaquiline ( 1 R,2S)- 1 -(6-Bromo-2-methoxy-3 -quinolyl)-4-dimethylamino-2-( 1 -naphthyl)- 1 -phenyl- butan-2-ol
  • bedaquiline (CAS no. 843663-66-1) and belongs to the group of quinoline derivatives that can be used as microbial inhibitors.
  • the salt bedaquiline fumarate (1:1) is suitable for treatment or prevention of resistant microbial infections, especially microbial tuberculosis infections.
  • Bedaquiline fumarate exists in one non-solvated crystalline form (Form A) and two pseudo- polymorphic forms B and C.
  • the invention provides a solid form of bedaquiline with citric acid and methods of its preparation.
  • the crystalline salt is prepared by a reaction of bedaquiline in the free base form with citric acid in a suitable solvent or mixtures of solvents.
  • the prepared salt has advantageous physical-chemical characteristics for use in the pharmaceutical industry and in formulation of new dosage forms.
  • FIG. 1 X-ray powder pattern of bedaquiline citrate (prepared in accordance with Process 2).
  • Figure 2. IR spectrum of bedaquiline citrate (prepared in accordance with Process 2).
  • a crystalline product is often stable, its required purity is easier to achieve and it dissolves more slowly.
  • This invention provides a crystalline salt of bedaquiline in the solid phase.
  • the invention provides a novel solid form of bedaquiline with citric acid that can be prepared and isolated in a crystalline form in adequate yields with high chemical purity.
  • This solid form can be both anhydrous or non-solvated and in the form of hydrates/solvates of the respective solvents.
  • the prepared novel solid form of bedaquiline may have various internal arrangements (polymorphism) with different physical-chemical properties depending on the conditions of its preparation. For this reason, the invention relates to the crystalline form of bedaquiline with citric acid or its mixtures in any ratio.
  • This solid form is suitable for preparation and isolation of bedaquiline with high chemical and optical purity.
  • the preparation of the solid form of bedaquiline of formula I is carried out by reaction of the free base of bedaquiline with citric acid.
  • the reaction is conducted in a suitable solvent, which can be ketones, esters, ethers, amides, nitriles or organic acids, alcohols, aliphatic and aromatic hydrocarbons, chlorinated hydrocarbons, water or their mixtures.
  • Aliphatic Q-C4 alcohols, esters or their mixtures are preferred.
  • the most commonly used solvents are isopropanol, acetonitrile, tetrahydrofuran or their mixtures.
  • the final product is typically precipitated or crystallized at temperatures in the range of -30°C to the boiling point of the solvent.
  • the crystalline form of bedaquiline citrate (according to Example 2) is characterized by the reflections presented in Table 1.
  • Table 1 includes reflections whose relative intensity value is higher than 1 percent.
  • the characteristic diffraction peaks of bedaquiline citrate in accordance with this invention are as follows: 10.3; 12.0; 13.1; 18.3; 19.7 and 22,0 ⁇ 0.2° 2-theta.
  • An example of the X-ray powder pattern is shown in Figure 1.
  • the melting point of bedaquiline citrate is 174°C (DSC).
  • a 10mm mask and a 1/4° fixed anti-dispersion slit were used.
  • the irradiated area of the sample is 10 mm, programmable divergence slits were used.
  • For the correction of the secondary array 0.02 rad Soller slits and a 5.0 anti-dispersion slit were used.
  • ATR (ZnSe - single reflection) infrared spectra of the powder samples were measured with an infrared spectrometer (Nicolet Nexus, Thermo, USA) equipped with a DTGS KBr detector, in the measurement range of 600-4000 cm '1 and the spectral resolution of 4.0 cm "1 .
  • the data were obtained at 64 spectrum accumulations.
  • the OMNIC 6.2 software was used to process the spectra.
  • the record of bedaquiline citrate was measured using a Discovery DSC device made by TA Instruments.
  • the sample charge in a standard Al pot (40 yiL) was 4-5 mg and the heating rate was 5°C/min.
  • As the carrier gas 5.0 N 2 was used at the flow rate of 50 ml/min.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une nouvelle forme solide de (1R,2S)-1-(6-bromo-2-méthoxy-3- quinolyl)-4-diméthylamino-2-(1-napthyl)-1-phényl-butan-2-ol de formule I, connue sous le nom de bédaquiline, et ses procédés de préparation.
PCT/CZ2016/000063 2015-06-09 2016-06-03 Sel de bédaquiline avec acide citrique WO2016198031A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ2015-391A CZ2015391A3 (cs) 2015-06-09 2015-06-09 Sůl bedaquilinu s kyselinou citronovou
CZPV2015-391 2015-06-09

Publications (1)

Publication Number Publication Date
WO2016198031A1 true WO2016198031A1 (fr) 2016-12-15

Family

ID=56463987

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2016/000063 WO2016198031A1 (fr) 2015-06-09 2016-06-03 Sel de bédaquiline avec acide citrique

Country Status (2)

Country Link
CZ (1) CZ2015391A3 (fr)
WO (1) WO2016198031A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004011436A1 (fr) 2002-07-25 2004-02-05 Janssen Pharmaceutica N.V. Derives de quinoleine et leur utilisation en tant qu'inhibiteurs mycobacteriens
WO2006125769A1 (fr) 2005-05-25 2006-11-30 Janssen Pharmaceutica N.V. Procede de preparation de (alpha s, beta r)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-1-naphtalenyl-beta-phenyl-3-quinoline-ethanol
WO2008068231A1 (fr) * 2006-12-05 2008-06-12 Janssen Pharmaceutica N.V. Sel de fumarate de (alpha s, bêta r)-6-bromo-alpha-[2-(diméthylamino)éthyl]-2-méthoxy-alpha-1-naphtalényl-bêta-phényl-3-quinoléineéthanol
WO2016058564A1 (fr) * 2014-10-16 2016-04-21 Zentiva, K.S. Sels de bédaquiline

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004011436A1 (fr) 2002-07-25 2004-02-05 Janssen Pharmaceutica N.V. Derives de quinoleine et leur utilisation en tant qu'inhibiteurs mycobacteriens
WO2006125769A1 (fr) 2005-05-25 2006-11-30 Janssen Pharmaceutica N.V. Procede de preparation de (alpha s, beta r)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-1-naphtalenyl-beta-phenyl-3-quinoline-ethanol
WO2008068231A1 (fr) * 2006-12-05 2008-06-12 Janssen Pharmaceutica N.V. Sel de fumarate de (alpha s, bêta r)-6-bromo-alpha-[2-(diméthylamino)éthyl]-2-méthoxy-alpha-1-naphtalényl-bêta-phényl-3-quinoléineéthanol
EP2086940A1 (fr) 2006-12-05 2009-08-12 Janssen Pharmaceutica N.V. Sel de fumarate de (alpha s, bêta r)-6-bromo-alpha-[2-(diméthylamino)éthyl]-2-méthoxy-alpha-1-naphtalényl-bêta-phényl-3-quinoléineéthanol
WO2016058564A1 (fr) * 2014-10-16 2016-04-21 Zentiva, K.S. Sels de bédaquiline

Also Published As

Publication number Publication date
CZ2015391A3 (cs) 2016-12-21

Similar Documents

Publication Publication Date Title
US10246418B2 (en) Crystal form of lenvatinib methanesulfonate salt and preparation method thereof
US9309226B2 (en) Crystalline form I of tyrosine kinase inhibitor dimaleate and preparation methods thereof
WO2017008773A1 (fr) Formes cristallines d'acide obéticholique
JP6349435B2 (ja) ７−｛（３ｓ、４ｓ）−３−［（シクロプロピルアミノ）メチル］−４−フルオロピロリジン−１−イル｝−６−フルオロ−１−（２−フルオロエチル）−８−メトキシ−４−オキソ−１、４−ジヒドロキノリン−３−カルボン酸の結晶
EP3256474B1 (fr) Sel de sulfate ibrutinib
JP2018501289A (ja) ネラチニブマレイン酸塩の新規な結晶形及びその製造方法
WO2017174044A1 (fr) Formes solides d'ibrutinib
JP2019104760A (ja) ベンズイミダゾール誘導体の新規結晶形及びその製造方法
WO2016192692A1 (fr) Formes solides d'alafénamide de ténofovir
WO2016127963A1 (fr) Formes solides de sels de palbociclib
WO2016058564A1 (fr) Sels de bédaquiline
US20240140910A1 (en) Method for producing centanafadine
WO2015068055A1 (fr) Procédé de préparation de dasatinib cristallin
WO2016169533A1 (fr) Forme solide d'aprémilast et un procédé pour sa préparation
WO2016206662A1 (fr) Hémisulfate d'ibrutinib
WO2016198031A1 (fr) Sel de bédaquiline avec acide citrique
US11203585B2 (en) Crystalline forms of lenalidomide
EP3328848A1 (fr) Formes solides de ceritinib base libre
JP5726830B2 (ja) ５−ヒドロキシ−１ｈ−イミダゾール−４−カルボキサミド・３／４水和物の結晶及びその製造方法
JP2016535045A (ja) （２Ｒ）−４−オキソ−４−［３−（トリフルオロメチル）−５，６−ジヒドロ［１，２，４］トリアゾロ［４，３−α］ピラジン−７（８Ｈ）−イル］−１−（２，４，５−トリフルオロフェニル）ブタン−２−アミンとＬ−酒石酸との塩の安定な多形
CN108718526B (zh) 尼达尼布盐的结晶变态和其制备方法
WO2016127962A1 (fr) Forme solide amorphe de suvorexant avec acide sulfurique
WO2016192691A1 (fr) Formes solides de daclatasvir
TWI592397B (zh) 卡維地洛硫酸鹽的結晶、其製備方法及其在醫藥上的應用
CZ200969A3 (cs) Nové soli desvenlafaxinu a zpusob jejich prípravy

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: 16740957

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: 16740957

Country of ref document: EP

Kind code of ref document: A1