WO2008075376A1 - Formes polymorphes du bortézomibe et leur procédé de préparation - Google Patents

Formes polymorphes du bortézomibe et leur procédé de préparation Download PDF

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Publication number
WO2008075376A1
WO2008075376A1 PCT/IN2007/000561 IN2007000561W WO2008075376A1 WO 2008075376 A1 WO2008075376 A1 WO 2008075376A1 IN 2007000561 W IN2007000561 W IN 2007000561W WO 2008075376 A1 WO2008075376 A1 WO 2008075376A1
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WO
WIPO (PCT)
Prior art keywords
bortezomib
peaks
polymorphic
product
onset
Prior art date
Application number
PCT/IN2007/000561
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English (en)
Other versions
WO2008075376A8 (fr
Inventor
Janaki Rama Rao Ravi
Muddasani Pulla Reddy
Bhujanga Rao Adibatla Kali Satya
Nannapaneni Benkaiah Chowdary
Original Assignee
Natco Pharma 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 Natco Pharma Limited filed Critical Natco Pharma Limited
Publication of WO2008075376A1 publication Critical patent/WO2008075376A1/fr
Publication of WO2008075376A8 publication Critical patent/WO2008075376A8/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
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds

Definitions

  • the present invention relates to the polymorphic Form-I and Form-II of bortezomib (1) and processes for preparation of the above said forms.
  • Bortezomib is an anti-neoplastic agent used in the treatment of multiple myeloma.
  • bortezomib is [(lR)-3-methyl-l-[[(2S)-l-oxp-3-phenyl-2- [(Pyrazinyl carbonyl)amino]propyl]-amino]butyl] boronic acid.
  • Bortezomib is introduced by Millennium Pharmaceuticals Inc., a U.S. based company.
  • Bortezomib (1) is a modified dipeptidyl boronic acid, and is a reversible inhibitor of the Chymotrypsin like activity of the 26s proteasome in mammalian cells. Bortezomib shows significant antitumor activity in human tumor xenograft models and is undergoing clinical evaluation.
  • the 26s proteasome is a large protein complex that degrades ubiquitinated proteins.
  • the ubiquitin proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homestasis within cells.
  • bortezomib is cytotoxic to a variety of cancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in non-clinical tumor models, including multiple myeloma.
  • the main objective of the present invention is to provide polymorphic Forms of bortezomib designated by us as Form I and Form II.
  • Present invention relates to the preparation of two polymorphic Forms I and II of bortezomib.
  • the polymorphs being characterized by: (1) The peaks appearing in powder X-ray diffraction pattern (XRD)
  • DSC Differential scanning calorimetry data
  • Polymorphic Form-I is characterized by the following data.
  • Peaks in the powder X-ray diffraction pattern are as given below.
  • a process for the preparation of Form I crystals of bortezomib of the Formula 1 having the characteristics given above which comprises dissolving bortezomib in solvents selected from ketones such as acetone or halogenated solvents such as methylene chloride, chloroform or nitriles such as acetonitrile at 25-30 0 C, adding anti solvents such as diisoprpyl ether or tert-butylmethl ether or n-hexane or n-heptane stirring of the resultant solution atlO-3O°C, and filtering of the crystals by conventional techniques.
  • solvents selected from ketones such as acetone or halogenated solvents such as methylene chloride, chloroform or nitriles such as acetonitrile at 25-30 0 C
  • anti solvents such as diisoprpyl ether or tert-butylmethl ether or n-hexane or
  • Peaks in the powder X-ray diffraction pattern are as given below.
  • a process for the preparation of Form II of bortezomib of the formula 1 having the characteristics given above which comprises dissolving bortezomib in solvents selected from esters such as ethyl acetate, isopropyl acetate at 70 0 C, cooling of the resultant solution to 25-30°c°C, and filtering of the crystals.
  • solvents selected from esters such as ethyl acetate, isopropyl acetate at 70 0 C
  • cooling of the resultant solution to 25-30°c°C
  • filtering of the crystals The novel forms of bortezomib may be formulated in a form suitable for oral administration or injection.
  • FIG.l Powder X-ray diffraction pattern of Form-I bortezomib
  • FIG.2 Infrared absorption spectrum of Form-I bortezomib
  • FIG.3 DSC thermogram of Form-I bortezomib
  • FIG.4 Powder X-ray diffraction pattern of Form-II bortezomib
  • FIG.5 Infrared absorption spectrum of Form-II bortezomib
  • FIG.6 DSC thermogram of Form-II bortezomib
  • X-ray powder diffraction spectra were measured on a Siemens d5000 x-ray powder diffracto-meter having a copper-k ⁇ radiation (1.5406a).
  • Present invention discloses two novel crystalline forms of bortezomib designated by us as Form-I and Form-II which are stable, reproducible, and useful for the treatment of multiple myeloma.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur deux nouvelles formes polymorphes stables du bortézomibe (formes I et II) et sur leur procédé de préparation. Le bortézomibe (1) est un agent anti-néoplasique utilisé dans le traitement du myélome multiple.
PCT/IN2007/000561 2006-12-18 2007-12-03 Formes polymorphes du bortézomibe et leur procédé de préparation WO2008075376A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2348/CHE/2006 2006-12-18
IN2348CH2006 2006-12-18

Publications (2)

Publication Number Publication Date
WO2008075376A1 true WO2008075376A1 (fr) 2008-06-26
WO2008075376A8 WO2008075376A8 (fr) 2010-04-15

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PCT/IN2007/000561 WO2008075376A1 (fr) 2006-12-18 2007-12-03 Formes polymorphes du bortézomibe et leur procédé de préparation

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WO (1) WO2008075376A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010539183A (ja) * 2007-09-12 2010-12-16 ドクター・レディーズ・ラボラトリーズ・リミテッド ボルテゾミブおよびその生成のためのプロセス
WO2011099018A1 (fr) * 2010-02-15 2011-08-18 Hetero Research Foundation Polymorphes de bortézomib
WO2011107912A1 (fr) 2010-03-04 2011-09-09 Ranbaxy Laboratories Limited Formes polymorphes de bortézomib
US8263578B2 (en) 2010-03-18 2012-09-11 Innopharma, Inc. Stable bortezomib formulations
US8497374B2 (en) 2011-05-12 2013-07-30 Scinopharm Taiwan, Ltd. Process for preparing and purifying bortezomib
EP2644189A1 (fr) 2012-03-27 2013-10-02 Innopharma, Inc. Formulations de bortézomib stable
WO2014076713A2 (fr) 2012-11-16 2014-05-22 Shilpa Medicare Limited Procédé de préparation de bortézomib cristallin
WO2014097306A1 (fr) 2012-12-21 2014-06-26 Natco Pharma Limited Forme polymorphe stable et pure du bortézomib
US8962572B2 (en) 2010-10-05 2015-02-24 Fresenius Kabi Usa, Llc Bortezomib formulations
US9061037B2 (en) 2010-03-18 2015-06-23 Innopharma, Inc. Stable bortezomib formulations
WO2015122702A1 (fr) * 2014-02-14 2015-08-20 Kyongbo Pharm. Co., Ltd. Nouvelle forme cristalline de bortézomib et procédé de préparation associé
WO2016085943A1 (fr) 2014-11-25 2016-06-02 Rastelli, Luca Utilisation d'inhibiteurs du système ubiquitine-protéasome pour le traitement de tumeurs associées à la neurofibromatose de type 2
EP3031811A1 (fr) 2014-12-09 2016-06-15 Teva Pharmaceuticals Ltd. Esters d'acide malique de bortézomib
US10023611B2 (en) * 2013-04-16 2018-07-17 Cipla Limited Process for the preparation of bortezomib mannitol ester
WO2019151133A1 (fr) * 2018-02-01 2019-08-08 日本化薬株式会社 Procédé de fabrication de cristaux de bortézomib
CN110642881A (zh) * 2019-10-18 2020-01-03 扬子江药业集团上海海尼药业有限公司 一种硼替佐米晶型m及其制备方法和用途
AU2018221670B2 (en) * 2017-02-17 2021-02-04 Fresenius Kabi Oncology Ltd. An improved process for the preparation of boronic acid esters
US11964993B2 (en) 2021-07-03 2024-04-23 Shilpa Pharma Lifesciences Limited Crystalline bortezomib process

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050240047A1 (en) * 2004-03-30 2005-10-27 Millennium Pharmaceuticals, Inc. Synthesis of boronic ester and acid compounds
WO2006101535A1 (fr) * 2005-03-23 2006-09-28 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Inhibition de la fonction du proteasome pour renforcer l’activite proapoptotique et antitumorale des cytokines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050240047A1 (en) * 2004-03-30 2005-10-27 Millennium Pharmaceuticals, Inc. Synthesis of boronic ester and acid compounds
WO2006101535A1 (fr) * 2005-03-23 2006-09-28 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Inhibition de la fonction du proteasome pour renforcer l’activite proapoptotique et antitumorale des cytokines

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010539183A (ja) * 2007-09-12 2010-12-16 ドクター・レディーズ・ラボラトリーズ・リミテッド ボルテゾミブおよびその生成のためのプロセス
WO2011099018A1 (fr) * 2010-02-15 2011-08-18 Hetero Research Foundation Polymorphes de bortézomib
WO2011107912A1 (fr) 2010-03-04 2011-09-09 Ranbaxy Laboratories Limited Formes polymorphes de bortézomib
US8263578B2 (en) 2010-03-18 2012-09-11 Innopharma, Inc. Stable bortezomib formulations
US9180093B2 (en) 2010-03-18 2015-11-10 Innopharma, Inc. Stable bortezomib formulations
US9107821B2 (en) 2010-03-18 2015-08-18 Innopharma, Inc. Stable bortezomib formulations
US9061037B2 (en) 2010-03-18 2015-06-23 Innopharma, Inc. Stable bortezomib formulations
US8962572B2 (en) 2010-10-05 2015-02-24 Fresenius Kabi Usa, Llc Bortezomib formulations
US8497374B2 (en) 2011-05-12 2013-07-30 Scinopharm Taiwan, Ltd. Process for preparing and purifying bortezomib
EP2644189A1 (fr) 2012-03-27 2013-10-02 Innopharma, Inc. Formulations de bortézomib stable
WO2014076713A3 (fr) * 2012-11-16 2014-07-24 Shilpa Medicare Limited Procédé de préparation de bortézomib cristallin
US9217001B2 (en) 2012-11-16 2015-12-22 Shilpa Medicare Limited Crystalline bortezomib process
WO2014076713A2 (fr) 2012-11-16 2014-05-22 Shilpa Medicare Limited Procédé de préparation de bortézomib cristallin
AU2013346322B2 (en) * 2012-11-16 2016-11-10 Shilpa Medicare Limited Crystalline Bortezomib process
JP2015536342A (ja) * 2012-11-16 2015-12-21 シルパ・メディケア・リミテッドＳｈｉｌｐａ Ｍｅｄｉｃａｒｅ Ｌｉｍｉｔｅｄ 結晶ボルテゾミブの方法
WO2014097306A1 (fr) 2012-12-21 2014-06-26 Natco Pharma Limited Forme polymorphe stable et pure du bortézomib
US10023611B2 (en) * 2013-04-16 2018-07-17 Cipla Limited Process for the preparation of bortezomib mannitol ester
WO2015122702A1 (fr) * 2014-02-14 2015-08-20 Kyongbo Pharm. Co., Ltd. Nouvelle forme cristalline de bortézomib et procédé de préparation associé
KR101763106B1 (ko) * 2014-02-14 2017-08-01 주식회사 경보제약 보르테조밉(Bortezomib)의 신규한 결정형 및 그의 제조방법
WO2016085943A1 (fr) 2014-11-25 2016-06-02 Rastelli, Luca Utilisation d'inhibiteurs du système ubiquitine-protéasome pour le traitement de tumeurs associées à la neurofibromatose de type 2
US10610563B2 (en) 2014-11-25 2020-04-07 Bioxcel Corporation Use of ubiquitin-proteasome system inhibitors for treatment of tumors associated with neurofibromatosis type-2
EP3031811A1 (fr) 2014-12-09 2016-06-15 Teva Pharmaceuticals Ltd. Esters d'acide malique de bortézomib
AU2018221670B2 (en) * 2017-02-17 2021-02-04 Fresenius Kabi Oncology Ltd. An improved process for the preparation of boronic acid esters
US11667654B2 (en) 2017-02-17 2023-06-06 Fresenius Kabi Oncology Ltd. Process for the preparation of boronic acid esters
JPWO2019151133A1 (ja) * 2018-02-01 2021-02-04 日本化薬株式会社 ボルテゾミブ結晶の製造方法
JP7263263B2 (ja) 2018-02-01 2023-04-24 日本化薬株式会社 ボルテゾミブ結晶の製造方法
WO2019151133A1 (fr) * 2018-02-01 2019-08-08 日本化薬株式会社 Procédé de fabrication de cristaux de bortézomib
CN110642881A (zh) * 2019-10-18 2020-01-03 扬子江药业集团上海海尼药业有限公司 一种硼替佐米晶型m及其制备方法和用途
US11964993B2 (en) 2021-07-03 2024-04-23 Shilpa Pharma Lifesciences Limited Crystalline bortezomib process

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