LT3325482T - Citotoksinių benzodiazepino darinių paruošimo būdai - Google Patents

Citotoksinių benzodiazepino darinių paruošimo būdai

Info

Publication number
LT3325482T
LT3325482T LTEP16745598.9T LT16745598T LT3325482T LT 3325482 T LT3325482 T LT 3325482T LT 16745598 T LT16745598 T LT 16745598T LT 3325482 T LT3325482 T LT 3325482T
Authority
LT
Lithuania
Prior art keywords
preparation
methods
benzodiazepine derivatives
cytotoxic benzodiazepine
cytotoxic
Prior art date
Application number
LTEP16745598.9T
Other languages
English (en)
Lithuanian (lt)
Inventor
Baudouin GÉRARD
Manami Shizuka
Michael Miller
Richard Silva
Original Assignee
Immunogen, 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 Immunogen, Inc. filed Critical Immunogen, Inc.
Publication of LT3325482T publication Critical patent/LT3325482T/lt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
    • C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
    • C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • 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
    • 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
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C07F7/1872—Preparation; Treatments not provided for in C07F7/20
    • C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Pyridine Compounds (AREA)
LTEP16745598.9T 2015-07-21 2016-07-21 Citotoksinių benzodiazepino darinių paruošimo būdai LT3325482T (lt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562195023P 2015-07-21 2015-07-21
US201662327973P 2016-04-26 2016-04-26
PCT/US2016/043414 WO2017015502A1 (en) 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives

Publications (1)

Publication Number Publication Date
LT3325482T true LT3325482T (lt) 2020-11-25

Family

ID=56557925

Family Applications (2)

Application Number Title Priority Date Filing Date
LTEP16745598.9T LT3325482T (lt) 2015-07-21 2016-07-21 Citotoksinių benzodiazepino darinių paruošimo būdai
LTEP16745961.9T LT3325483T (lt) 2015-07-21 2016-07-21 Citotoksinių benzodiazepino darinių gavimo būdai

Family Applications After (1)

Application Number Title Priority Date Filing Date
LTEP16745961.9T LT3325483T (lt) 2015-07-21 2016-07-21 Citotoksinių benzodiazepino darinių gavimo būdai

Country Status (23)

Country Link
US (11) US9890179B2 (enExample)
EP (7) EP3325483B1 (enExample)
JP (8) JP6787995B2 (enExample)
KR (5) KR20180038460A (enExample)
CN (5) CN113087763A (enExample)
AU (7) AU2016297608B2 (enExample)
CA (4) CA3227588A1 (enExample)
CY (2) CY1122553T1 (enExample)
DK (2) DK3325483T3 (enExample)
ES (4) ES2933376T3 (enExample)
HK (1) HK1252322A1 (enExample)
HR (1) HRP20201479T1 (enExample)
HU (1) HUE051541T2 (enExample)
IL (10) IL286788B2 (enExample)
LT (2) LT3325482T (enExample)
PL (2) PL3325483T3 (enExample)
PT (2) PT3325482T (enExample)
RS (2) RS60840B1 (enExample)
RU (3) RU2727151C2 (enExample)
SG (2) SG10202009354SA (enExample)
SI (2) SI3325482T1 (enExample)
SM (2) SMT202000004T1 (enExample)
WO (3) WO2017015495A1 (enExample)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180038460A (ko) 2015-07-21 2018-04-16 이뮤노젠 아이엔씨 세포독성 벤조다이아제핀 유도체의 제조 방법
EP3433875B1 (de) 2016-03-22 2022-05-04 EV Group E. Thallner GmbH Verfahren zum bonden von substraten
CN118359704A (zh) 2016-10-19 2024-07-19 英温拉公司 抗体构建体
EA201991204A1 (ru) 2016-12-22 2019-12-30 Университа Дельи Студи Манья Греча Катандзаро Моноклональное антитело против уникального сиалогликозилированного опухолеассоциированного эпитопа cd43
AU2018213202B2 (en) 2017-01-25 2022-03-24 Immunogen, Inc. Methods of preparing cytotoxic benzodiazepine derivatives
WO2019234136A1 (en) 2018-06-05 2019-12-12 King's College London Btnl3/8 targeting constructs for delivery of payloads to the gastrointestinal system
SG11202104423XA (en) * 2018-11-12 2021-05-28 Immunogen Inc Methods of preparing cytotoxic benzodiazepine derivatives
CN112996792B (zh) * 2018-11-12 2024-04-26 伊缪诺金公司 制备细胞毒性苯并二氮杂卓衍生物的方法
CN113661172A (zh) * 2019-03-29 2021-11-16 伊缪诺金公司 用于抑制异常细胞生长或治疗增生性疾病的细胞毒性双苯并二氮杂䓬衍生物及其与细胞结合剂的缀合物
AU2023298568A1 (en) 2022-06-30 2025-01-09 Toray Industries, Inc. Pharmaceutical composition for cancer treatment and/or prevention

Family Cites Families (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3860600A (en) 1972-07-10 1975-01-14 Sterling Drug Inc Octahydropyrrido{8 2,1-c{9 {8 1,4{9 benzodiazepines
US3763183A (en) 1972-07-10 1973-10-02 Sterling Drug Inc 1,2,3,10,11,11a-hexahydro-5h-pyrrolo (2,1-c)(1,4)benzodiazepines
US4678784A (en) 1984-04-11 1987-07-07 Mcneilab, Inc. Method for the treatment of LHRH diseases and conditions
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
GB9205051D0 (en) 1992-03-09 1992-04-22 Cancer Res Campaign Tech Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them
ES2149768T3 (es) 1992-03-25 2000-11-16 Immunogen Inc Conjugados de agentes enlazantes de celulas derivados de cc-1065.
DK1193270T3 (da) 1998-08-27 2003-09-15 Spirogen Ltd Pyrrolobenzodiazepiner
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
CA2388063C (en) 1999-11-24 2010-06-08 Immunogen, Inc. Cytotoxic agents comprising taxanes and their therapeutic use
US6548042B2 (en) * 2000-08-07 2003-04-15 Arstad Erik Bis-phosphonate compounds
UA75093C2 (en) * 2000-10-06 2006-03-15 Dimensional Pharm Inc Aminopyridinyl-,aminoguanidinyl-, and alkoxyguanidinesubstituted phenylsubstituted phenylacetamides as protease inhibitors
US6441163B1 (en) 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US6716821B2 (en) 2001-12-21 2004-04-06 Immunogen Inc. Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
MXPA05001390A (es) 2002-08-02 2005-07-29 Immunogen Inc Agentes citotoxicos que contienen taxanos potentes novedosos y su uso terapeutico.
JP2006500364A (ja) 2002-08-16 2006-01-05 イムノージェン インコーポレーテッド 高い反応性と溶解度を有する架橋剤および小分子薬物の標的化送達用コンジュゲートの調製におけるそれらの使用
RU2314309C2 (ru) 2003-03-31 2008-01-10 Каунсил Оф Сайентифик Энд Индастриал Рисерч Пирроло [2.1-c][1.4] бензодиазепины, способ их получения и фармацевтическая композиция на их основе
RU2338747C2 (ru) 2003-03-31 2008-11-20 Каунсил Оф Сайентифик Энд Индастриал Рисерч ДИМЕРЫ ПИРРОЛО [2, 1-c][1, 4] БЕНЗОДИАЗЕПИНА В КАЧЕСТВЕ ПРОТИВООПУХОЛЕВЫХ СРЕДСТВ И СПОСОБ ИХ ПОЛУЧЕНИЯ
AU2003215810B2 (en) 2003-03-31 2009-06-18 Council Of Scientific And Industrial Research Pyrrolo((2,1-c)(1,4) benzodiazepines dimers as antitumour agents and process thereof
AU2003215821B2 (en) 2003-03-31 2009-04-23 Council Of Scientific And Industrial Research Non-cross-linking pyrrolo(2,1-c)(1,4)benzodiazepines as potential antitumour agents and process thereof
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
ATE516288T1 (de) 2003-10-22 2011-07-15 Us Gov Health & Human Serv Pyrrolobenzodiazepinderivate, zusammensetzungen, die diese enthalten, und damit in zusammenhang stehende verfahren
WO2005063759A1 (en) 2003-12-31 2005-07-14 Council Of Scientific And Industrial Research PROCESS FOR PREPARING PYRROLO[2, 1-c] [1, 4] BENZODIAZEPINE HYBRIDS
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
CA2558195C (en) * 2004-03-01 2012-11-06 Spirogen Limited 11-hydroxy-5h-pyrrolo[2,1-c][1,4]benzodiazepin-5-one derivatives as key intermediates for the preparation of c2 substituted pyrrolobenzodiazepines
GB0410725D0 (en) 2004-05-13 2004-06-16 Spirogen Ltd Pyrrolobenzodiazepine therapeutic agents
GB0412492D0 (en) * 2004-06-04 2004-07-07 Sterix Ltd Compound
GB0508084D0 (en) * 2005-04-21 2005-06-01 Spirogen Ltd Pyrrolobenzodiazepines
AU2006238686B2 (en) 2005-04-21 2011-10-06 Medimmune Limited Pyrrolobenzodiazepines
ATE427949T1 (de) 2005-10-05 2009-04-15 Spirogen Ltd 4-a4-(5-oxo-2,3,5,11a-tetrahydro-5h-pyrrolo a2, 1-cua1,4ubenzodiazepin-8-yloxy)-butyrylaminou-1 - pyrrol-2-carbonsaurealkylesterderivate und verwandte verbindung zur behandlung einer proliferativen erkrankung
EP1979349B1 (en) * 2005-12-21 2010-07-28 Abbott Laboratories Anti-viral compounds
DK1813614T3 (da) 2006-01-25 2012-01-23 Sanofi Sa Cytotoksiske midler, der omfatter nye tomaymycinderivater
WO2007093873A1 (en) 2006-02-13 2007-08-23 Council Of Scientific And Industrial Research Bis-pyrr0l0[2,l-c] [1, 4] benzodiazepine- anthraquinone conjugates as antitumour agents and a process for the preparation thereof
HRP20140172T1 (hr) 2006-05-30 2014-03-28 Genentech, Inc. Protutijela i imunokonjugati kao i njihove uporabe
DK2019104T3 (da) 2007-07-19 2013-12-16 Sanofi Sa Cytotoksiske midler, der omfatter nye tomaymycinderivater, og terapeutisk anvendelse deraf
ATE543826T1 (de) 2007-08-01 2012-02-15 Council Scient Ind Res Als selektive antitumormittel geeignete pyrroloä2,1-cüä1,4übenzodiazepinglycosid-prodru s
CN102076717B (zh) 2008-04-30 2016-02-03 伊缪诺金公司 交联剂和它们的用途
BRPI0911442A2 (pt) 2008-04-30 2019-03-12 Immunogen, Inc. conjugados potentes e ligantes hidrofílicos
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
GB0822260D0 (en) * 2008-12-05 2009-01-14 Merten Christoph Assay
EP2383263B1 (en) * 2008-12-30 2014-04-16 Industry-academic Cooperation Foundation, Chosun University Novel thiazolidinedione derivative and use thereof
US8426402B2 (en) 2009-02-05 2013-04-23 Immunogen, Inc. Benzodiazepine derivatives
JP2013506709A (ja) 2009-10-06 2013-02-28 イミュノジェン・インコーポレーテッド 有効なコンジュゲートおよび親水性リンカー
US8314250B2 (en) * 2009-11-24 2012-11-20 Hoffmann-La Roche Inc. Sultam derivatives
WO2011071078A1 (ja) * 2009-12-08 2011-06-16 国立大学法人岐阜大学 芳香族化合物、並びに、それを用いたオリゴヌクレオチド誘導体合成用修飾担体、オリゴヌクレオチド誘導体及びオリゴヌクレオチド構築物
US8962279B2 (en) * 2009-12-30 2015-02-24 Intel Corporation Solid-phase chelators and electronic biosensors
SG10201501062SA (en) * 2010-02-11 2015-04-29 Celgene Corp Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
SG10201501342UA (en) 2010-02-24 2015-04-29 Immunogen Inc Folate receptor 1 antibodies and immunoconjugates and uses thereof
US20110256157A1 (en) 2010-04-15 2011-10-20 Spirogen Limited Pyrrolobenzodiazepines and conjugates thereof
NZ602932A (en) * 2010-04-15 2014-08-29 Seattle Genetics Inc Targeted pyrrolobenzodiazapine conjugates
CN102971329B (zh) 2010-04-15 2016-06-29 麦迪穆有限责任公司 用于治疗增殖性疾病的吡咯并苯并二氮杂卓
IL279304B (en) 2011-02-15 2022-07-01 Immunogen Inc Method for producing an indolinobenzodiazepine
CN102234253B (zh) * 2011-06-02 2013-07-03 重庆莱美药业股份有限公司 一种制备非布索坦中间体的方法
EP2887965A1 (en) 2012-08-22 2015-07-01 ImmunoGen, Inc. Cytotoxic benzodiazepine derivatives
CN105683163B (zh) * 2013-10-04 2018-11-09 诺华股份有限公司 RNA干扰中使用的RNAi剂的3’端帽
CN104628772A (zh) 2013-11-07 2015-05-20 四川恒康发展有限责任公司 一种抗肿瘤前药及其激活剂、组合物和应用
CN103664896B (zh) * 2013-11-25 2016-03-02 济南精合医药科技有限公司 一种抗肿瘤分子靶向药物克里唑替尼的合成工艺方法
PT3189056T (pt) * 2014-09-03 2020-09-04 Immunogen Inc Derivados citotóxicos de benzodiazepina
EP3189057A1 (en) 2014-09-03 2017-07-12 ImmunoGen, Inc. Cytotoxic benzodiazepine derivatives
JP2017529837A (ja) * 2014-09-03 2017-10-12 イミュノジェン・インコーポレーテッド 細胞結合剤及び細胞毒性剤を含む複合体
KR20180038460A (ko) 2015-07-21 2018-04-16 이뮤노젠 아이엔씨 세포독성 벤조다이아제핀 유도체의 제조 방법
DK3380525T3 (da) * 2015-11-25 2024-01-29 Immunogen Inc Farmaceutiske formuleringer og fremgangsmåder til anvendelse deraf

Also Published As

Publication number Publication date
EP3325482A1 (en) 2018-05-30
EP3325483B1 (en) 2019-10-02
SG10202106529XA (en) 2021-07-29
IL286788B2 (en) 2024-01-01
RU2018105756A3 (enExample) 2019-12-23
US9890179B2 (en) 2018-02-13
JP7334228B2 (ja) 2023-08-28
KR20240055894A (ko) 2024-04-29
ES2933376T3 (es) 2023-02-06
IL294651B2 (en) 2024-02-01
EP3653628B1 (en) 2022-09-14
AU2016297087A1 (en) 2018-02-08
CN113004288A (zh) 2021-06-22
CY1123390T1 (el) 2022-03-24
ES2820358T3 (es) 2021-04-20
IL283355A (en) 2021-07-29
HK1252322A1 (zh) 2019-05-24
ES2959741T3 (es) 2024-02-28
IL256854A (en) 2018-03-29
US20170050985A1 (en) 2017-02-23
CY1122553T1 (el) 2021-01-27
PT3325482T (pt) 2020-09-24
KR20240055903A (ko) 2024-04-29
AU2021202403A1 (en) 2021-05-20
IL276631B (en) 2021-10-31
RU2746322C2 (ru) 2021-04-12
AU2016297608B2 (en) 2021-02-18
RU2018105752A (ru) 2019-08-21
RU2018105609A3 (enExample) 2020-04-30
JP2018524387A (ja) 2018-08-30
JP2023162264A (ja) 2023-11-08
IL294651A (en) 2022-09-01
RS60840B1 (sr) 2020-10-30
JP6995178B2 (ja) 2022-02-21
CN108026103A (zh) 2018-05-11
AU2016297087B2 (en) 2021-02-18
IL256860A (en) 2018-03-29
IL305279A (en) 2023-10-01
IL256861B (en) 2020-08-31
PL3325483T3 (pl) 2020-05-18
EP3325485A1 (en) 2018-05-30
EP3778602B1 (en) 2023-07-12
JP2021035958A (ja) 2021-03-04
EP4286387A2 (en) 2023-12-06
US20210171547A1 (en) 2021-06-10
WO2017015502A8 (en) 2017-03-02
CN108055844A (zh) 2018-05-18
CN108290895A (zh) 2018-07-17
IL276631A (en) 2020-09-30
DK3325483T3 (da) 2020-01-20
US20210171546A1 (en) 2021-06-10
EP3325485B1 (en) 2020-04-08
US9873708B2 (en) 2018-01-23
AU2016297608A1 (en) 2018-02-08
IL276630B (en) 2021-06-30
EP3653628A1 (en) 2020-05-20
US20170051011A1 (en) 2017-02-23
EP4286387A3 (en) 2024-02-21
KR102660070B1 (ko) 2024-04-24
AU2023201339A1 (en) 2023-04-06
AU2021202403B2 (en) 2022-12-08
HK1252321A1 (en) 2019-05-24
US20190389883A1 (en) 2019-12-26
RU2018105756A (ru) 2019-08-21
IL294651B1 (en) 2023-10-01
CN113087763A (zh) 2021-07-09
PL3325482T3 (pl) 2021-01-11
IL256861A (en) 2018-03-29
LT3325483T (lt) 2020-01-27
KR102659706B1 (ko) 2024-04-23
CA2991305C (en) 2024-03-12
HK1252323A1 (en) 2019-05-24
CA2991305A1 (en) 2017-01-26
SMT202000506T1 (it) 2020-11-10
AU2016297607A1 (en) 2018-02-08
SMT202000004T1 (it) 2020-03-13
US10392407B2 (en) 2019-08-27
US10081640B2 (en) 2018-09-25
JP6787995B2 (ja) 2020-11-18
JP6858745B2 (ja) 2021-04-14
AU2021203148B2 (en) 2023-01-12
IL305989A (en) 2023-11-01
HRP20201479T1 (hr) 2020-12-11
SI3325483T1 (sl) 2020-03-31
CN108290895B (zh) 2021-03-19
RU2018105752A3 (enExample) 2019-12-30
SG10202009354SA (en) 2020-11-27
ES2764548T3 (es) 2020-06-03
IL276630A (en) 2020-09-30
RU2727151C2 (ru) 2020-07-21
PT3325483T (pt) 2020-01-15
US20190010169A1 (en) 2019-01-10
RS59806B1 (sr) 2020-02-28
SI3325482T1 (sl) 2020-11-30
US11420982B2 (en) 2022-08-23
EP4163284A1 (en) 2023-04-12
US10787463B2 (en) 2020-09-29
JP2018522018A (ja) 2018-08-09
DK3325482T3 (da) 2020-09-28
IL283355B (en) 2022-08-01
WO2017015496A1 (en) 2017-01-26
IL256860B (en) 2020-08-31
JP2021100959A (ja) 2021-07-08
CA3227588A1 (en) 2017-01-26
JP2023166434A (ja) 2023-11-21
JP2022046542A (ja) 2022-03-23
JP7337114B2 (ja) 2023-09-01
US20190112320A1 (en) 2019-04-18
US20230257400A1 (en) 2023-08-17
US20180201626A1 (en) 2018-07-19
RU2018105609A (ru) 2019-08-26
KR20180038461A (ko) 2018-04-16
IL286788A (en) 2021-10-31
KR20180026741A (ko) 2018-03-13
CN108026103B (zh) 2021-04-16
KR20180038460A (ko) 2018-04-16
US10899775B2 (en) 2021-01-26
US20200017526A1 (en) 2020-01-16
EP3325482B1 (en) 2020-06-24
AU2021203148A1 (en) 2021-06-10
EP3778602A1 (en) 2021-02-17
AU2023202221A1 (en) 2023-05-04
US20170050986A1 (en) 2017-02-23
WO2017015495A1 (en) 2017-01-26
US10370389B2 (en) 2019-08-06
CA2992082A1 (en) 2017-01-26
JP2018526340A (ja) 2018-09-13
IL286788B1 (en) 2023-09-01
EP3325483A1 (en) 2018-05-30
WO2017015502A1 (en) 2017-01-26
CA2991326A1 (en) 2017-01-26
HUE051541T2 (hu) 2021-03-01

Similar Documents

Publication Publication Date Title
IL283777A (en) Methods for formulating antibody drug conjugate compositions
SG11201706729SA (en) Derivatives of sobetirome
DK3189056T3 (da) Cytotoksiske benzodiazepinderivater
IL286788B1 (en) Methods for the preparation of cytotoxic benzodiazepine compounds
HRP20181650T1 (hr) Biciklički heterociklički derivati kao inhibitori bromodomene
HUE059158T2 (hu) Eljárás pridopidin elõállítására
HUE050974T2 (hu) Eljárás pirimidinszulfamid-származékok elõállítására
PT3457851T (pt) Derivados de sobetiroma
LT3212237T (lt) Metotreksato vaistinė forma
IL250613B (en) Substituted bicyclic compounds
FR3023290B1 (fr) Derives de flavaglines
IL287119B1 (en) Bryostatin compounds and methods of preparing the same
LT3573948T (lt) Citotoksinių benzodiazepino darinių paruošimo būdai
IL251559A0 (en) Pharmaceutical preparations of the history of aminodihydrothiazines from Amano
LT3253772T (lt) Diosmino ruošimo būdas
GB201513979D0 (en) Synthesis of benzodiazepine derivatives
EP3344338A4 (en) PULMONARY RELEASE OF PROGESTOGEN
HRP20182065T1 (hr) Postupak za pripremu penama
FR3023706B1 (fr) Orthese de genou
GB201417646D0 (en) Formulations of phosphate derivatives
ES1138388Y (es) Prenda de vestir perfeccionada