SMT202000506T1 - Metodi per preparare derivati benzodiazepinici citotossici - Google Patents

Metodi per preparare derivati benzodiazepinici citotossici

Info

Publication number
SMT202000506T1
SMT202000506T1 SM20200506T SMT202000506T SMT202000506T1 SM T202000506 T1 SMT202000506 T1 SM T202000506T1 SM 20200506 T SM20200506 T SM 20200506T SM T202000506 T SMT202000506 T SM T202000506T SM T202000506 T1 SMT202000506 T1 SM T202000506T1
Authority
SM
San Marino
Prior art keywords
methods
benzodiazepine derivatives
cytotoxic benzodiazepine
preparing cytotoxic
preparing
Prior art date
Application number
SM20200506T
Other languages
English (en)
Italian (it)
Inventor
Baudouin Gérard
Manami Shizuka
Michael Louis Miller
Richard A 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 SMT202000506T1 publication Critical patent/SMT202000506T1/it

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
    • 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
    • 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
    • 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 Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pyridine Compounds (AREA)
SM20200506T 2015-07-21 2016-07-21 Metodi per preparare derivati benzodiazepinici citotossici SMT202000506T1 (it)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562195023P 2015-07-21 2015-07-21
US201662327973P 2016-04-26 2016-04-26
EP16745598.9A EP3325482B1 (en) 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives
PCT/US2016/043414 WO2017015502A1 (en) 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives

Publications (1)

Publication Number Publication Date
SMT202000506T1 true SMT202000506T1 (it) 2020-11-10

Family

ID=56557925

Family Applications (2)

Application Number Title Priority Date Filing Date
SM20200004T SMT202000004T1 (it) 2015-07-21 2016-07-21 Metodi di preparazione dei derivati citotossici di benzodiazepina
SM20200506T SMT202000506T1 (it) 2015-07-21 2016-07-21 Metodi per preparare derivati benzodiazepinici citotossici

Family Applications Before (1)

Application Number Title Priority Date Filing Date
SM20200004T SMT202000004T1 (it) 2015-07-21 2016-07-21 Metodi di preparazione dei derivati citotossici di benzodiazepina

Country Status (23)

Country Link
US (11) US9890179B2 (OSRAM)
EP (7) EP3325485B1 (OSRAM)
JP (8) JP6858745B2 (OSRAM)
KR (5) KR20240055903A (OSRAM)
CN (5) CN113087763A (OSRAM)
AU (7) AU2016297087B2 (OSRAM)
CA (4) CA3227588A1 (OSRAM)
CY (2) CY1122553T1 (OSRAM)
DK (2) DK3325482T3 (OSRAM)
ES (4) ES2933376T3 (OSRAM)
HK (1) HK1252322A1 (OSRAM)
HR (1) HRP20201479T1 (OSRAM)
HU (1) HUE051541T2 (OSRAM)
IL (10) IL286788B2 (OSRAM)
LT (2) LT3325483T (OSRAM)
PL (2) PL3325483T3 (OSRAM)
PT (2) PT3325483T (OSRAM)
RS (2) RS60840B1 (OSRAM)
RU (3) RU2746322C2 (OSRAM)
SG (2) SG10202106529XA (OSRAM)
SI (2) SI3325482T1 (OSRAM)
SM (2) SMT202000004T1 (OSRAM)
WO (3) WO2017015495A1 (OSRAM)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI3325482T1 (sl) 2015-07-21 2020-11-30 Immunogen, Inc. Postopki za pripravo citotoksičnih benzodiazepinskih derivatov
US12131907B2 (en) 2016-03-22 2024-10-29 Ev Group E. Thallner Gmbh Device and method for bonding of substrates
CA3041254A1 (en) 2016-10-19 2018-04-26 Invenra Inc. Antibody constructs
KR102312222B1 (ko) 2016-12-22 2021-10-12 우니베르시따 델리 스투디 만냐 그레챠 카탄차로 Ｃｄ43의 독특한 시알로글리코실화된 암-연관 에피토프를 표적으로 하는 모노클로날 항체
SG11201906666QA (en) 2017-01-25 2019-08-27 Immunogen Inc Methods of preparing cytotoxic benzodiazepine derivatives
IL322895A (en) 2018-06-05 2025-10-01 King S College London Btnl3/8-targeted constructs for delivery of cargo to the digestive system
SG11202104423XA (en) * 2018-11-12 2021-05-28 Immunogen Inc Methods of preparing cytotoxic benzodiazepine derivatives
KR20210098470A (ko) * 2018-11-12 2021-08-10 이뮤노젠 아이엔씨 세포독성 벤조디아제핀 유도체의 제조 방법
US20230094471A1 (en) * 2019-03-29 2023-03-30 Immunogen, Inc. Cytotoxic bis-benzodiazepine derivatives and conjugates thereof with cell-binding agents for inhibiting abnormal cell growth or for treating proliferative diseases
WO2024005123A1 (ja) 2022-06-30 2024-01-04 東レ株式会社 癌の治療及び／又は予防用医薬組成物

Family Cites Families (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US3860600A (en) 1972-07-10 1975-01-14 Sterling Drug Inc Octahydropyrrido{8 2,1-c{9 {8 1,4{9 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
DE69231123T2 (de) 1992-03-25 2001-02-15 Immunogen Inc Konjugaten von Zell-bindender Mittel und Derivaten von CC-1065
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
ES2244210T3 (es) 1998-08-27 2005-12-01 Spirogen Limited Pirrolobenzodiazepinas.
PT1242401E (pt) 1999-11-24 2007-03-30 Immunogen Inc Agentes citotóxicos compreendendo taxanos e o seu uso terapêutico
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
CA2494074A1 (en) 2002-08-02 2004-02-12 Immunogen, Inc. Cytotoxic agents containing novel potent taxanes and their therapeutic use
CA2495795C (en) 2002-08-16 2011-12-13 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
DE60326060D1 (de) 2003-03-31 2009-03-19 Council Scient Ind Res Nichtvernetzende pyrroloä2,1-cüä1,4übenzodiazepine als potentielle antitumor-agentien und ihre herstellung
ATE413407T1 (de) 2003-03-31 2008-11-15 Council Scient Ind Res Pyrrolo(2,1-c)(1,4)benzodiazepin-dimere als antitumormittel und verfahren dafür
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
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
AU2004284075A1 (en) 2003-10-22 2005-05-06 Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Pyrrolobenzodiazepine derivatives, compositions comprising the same and methods related thereto
JP4520411B2 (ja) 2003-12-31 2010-08-04 カウンシル オブ サイエンティフィク アンド インダストリアル リサーチ ピロロ［２，１−ｃ］［１，４］ベンゾジアゼピン・ハイブリッドの調製方法
ES2381858T3 (es) * 2004-03-01 2012-06-01 Spirogen Limited Derivados de 11-hidroxi-5H-pirrolo[2,1-C][1,4]benzodiazepin-5-ona como intermedios clave para la preparación de pirrolobenzodiazepinas sustituidas en C2
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd 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
WO2006111759A1 (en) 2005-04-21 2006-10-26 Spirogen Limited Pyrrolobenzodiazepines
DE602006006199D1 (de) 2005-10-05 2009-05-20 Spirogen Ltd 4-ä4-(5-oxo-2,3,5,11a-tetrahydro-5h-pyrrolo ä2, 1-cüä1,4übenzodiazepin-8-yloxy)-butyrylaminoü-1h-pyrrol-2-carbonsäurealkylesterderivate und verwandte verbindung zur behandlung einer proliferativen erkrankung
ATE475660T1 (de) * 2005-12-21 2010-08-15 Abbott Lab Antivirale verbindungen
PL1813614T3 (pl) 2006-01-25 2012-03-30 Sanofi Sa Środki cytotoksyczne zawierające nowe pochodne tomaymycyny
US7465724B2 (en) 2006-02-13 2008-12-16 Council Of Scientific And Industrial Research Bis-pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates and a process for the preparation thereof
RS54163B1 (sr) 2006-05-30 2015-12-31 Genentech Inc. Anti-cd22 antitela, njihovi imunokonjugati i njihova upotreba
PT2019104E (pt) 2007-07-19 2013-12-03 Sanofi Sa Agentes citotóxicos compreendendo novos derivados de tomaimicina e sua utilização terapêutica
JP5404624B2 (ja) 2007-08-01 2014-02-05 カウンスィル オブ サイエンティフィック アンド インダストリアル リサーチ 選択的な抗腫瘍薬として有用なピロロ［２，１−ｃ］［１，４］ベンゾジアゼピン−グリコシドプロドラッグ
KR101764927B1 (ko) 2008-04-30 2017-08-03 이뮤노젠 아이엔씨 가교제 및 그 용도
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
CN108727407B (zh) 2009-02-05 2022-01-28 伊缪诺金公司 新型苯并二氮杂䓬衍生物
CN102596922A (zh) 2009-10-06 2012-07-18 免疫基因公司 有效的缀合物和亲水性连接体
US8314250B2 (en) * 2009-11-24 2012-11-20 Hoffmann-La Roche Inc. Sultam derivatives
EP2511260B1 (en) * 2009-12-08 2015-07-29 Gifu University Aromatic compound, modification carrier that uses same and is used for synthesizing an oligonucleotide derivative, oligonucleotide derivative, and oligonucleotide construct
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
TWI796132B (zh) 2010-02-24 2023-03-11 美商免疫遺傳股份有限公司 葉酸受體１抗體類和免疫共軛物類及彼等之用途
TWI540136B (zh) 2010-04-15 2016-07-01 梅迪繆思有限公司 吡咯并苯并二氮呯及其共軛物
KR101671360B1 (ko) * 2010-04-15 2016-11-01 시애틀 지네틱스, 인크. 표적화된 피롤로벤조디아제핀 접합체
JP5875083B2 (ja) 2010-04-15 2016-03-02 メディミューン リミテッド 増殖性疾患治療用ピロロベンゾジアゼピン
WO2012112708A1 (en) * 2011-02-15 2012-08-23 Immunogen, Inc. Cytotoxic benzodiazepine derivatives and methods of preparation
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
EP3722277A3 (en) * 2013-10-04 2021-01-20 Novartis AG 3'end caps for rna-interferring agents for use in rna
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
US9381256B2 (en) 2014-09-03 2016-07-05 Immunogen, Inc. Cytotoxic benzodiazepine derivatives
ES2815353T3 (es) 2014-09-03 2021-03-29 Immunogen Inc Derivados de benzodiazepina citotóxicos
KR102638901B1 (ko) 2014-09-03 2024-02-22 이뮤노젠 아이엔씨 세포-결합제 및 세포독성 약물을 포함하는 콘주게이트
SI3325482T1 (sl) 2015-07-21 2020-11-30 Immunogen, Inc. Postopki za pripravo citotoksičnih benzodiazepinskih derivatov
JP2019501139A (ja) * 2015-11-25 2019-01-17 イミュノジェン・インコーポレーテッド 医薬製剤及びその使用

Also Published As

Publication number Publication date
RU2018105752A3 (OSRAM) 2019-12-30
WO2017015502A8 (en) 2017-03-02
AU2016297608A1 (en) 2018-02-08
US20190389883A1 (en) 2019-12-26
IL256860B (en) 2020-08-31
JP2022046542A (ja) 2022-03-23
IL294651B2 (en) 2024-02-01
RU2727151C2 (ru) 2020-07-21
SI3325482T1 (sl) 2020-11-30
IL286788A (en) 2021-10-31
EP3325483B1 (en) 2019-10-02
EP3653628B1 (en) 2022-09-14
KR102659706B1 (ko) 2024-04-23
PT3325483T (pt) 2020-01-15
SI3325483T1 (sl) 2020-03-31
IL276631B (en) 2021-10-31
PL3325482T3 (pl) 2021-01-11
IL276630A (en) 2020-09-30
IL256860A (en) 2018-03-29
IL305279A (en) 2023-10-01
PT3325482T (pt) 2020-09-24
LT3325483T (lt) 2020-01-27
EP4286387A2 (en) 2023-12-06
CY1123390T1 (el) 2022-03-24
ES2820358T3 (es) 2021-04-20
JP2021100959A (ja) 2021-07-08
EP3325485A1 (en) 2018-05-30
CN108290895B (zh) 2021-03-19
RU2018105756A (ru) 2019-08-21
AU2016297607A1 (en) 2018-02-08
SG10202009354SA (en) 2020-11-27
CA2991305A1 (en) 2017-01-26
EP4163284A1 (en) 2023-04-12
SG10202106529XA (en) 2021-07-29
RU2018105609A (ru) 2019-08-26
PL3325483T3 (pl) 2020-05-18
US20170051011A1 (en) 2017-02-23
IL256861A (en) 2018-03-29
JP2018522018A (ja) 2018-08-09
HK1252322A1 (zh) 2019-05-24
HRP20201479T1 (hr) 2020-12-11
US20210171547A1 (en) 2021-06-10
JP6858745B2 (ja) 2021-04-14
IL305989A (en) 2023-11-01
EP3325483A1 (en) 2018-05-30
AU2021202403B2 (en) 2022-12-08
US20170050986A1 (en) 2017-02-23
KR20180038461A (ko) 2018-04-16
JP7337114B2 (ja) 2023-09-01
CN108290895A (zh) 2018-07-17
CA3227588A1 (en) 2017-01-26
ES2933376T3 (es) 2023-02-06
IL286788B2 (en) 2024-01-01
JP6995178B2 (ja) 2022-02-21
CN108055844A (zh) 2018-05-18
US20230257400A1 (en) 2023-08-17
JP2023166434A (ja) 2023-11-21
CN113087763A (zh) 2021-07-09
WO2017015496A1 (en) 2017-01-26
AU2023202221A1 (en) 2023-05-04
DK3325482T3 (da) 2020-09-28
EP4286387A3 (en) 2024-02-21
IL294651A (en) 2022-09-01
KR20240055894A (ko) 2024-04-29
EP3325482B1 (en) 2020-06-24
US11420982B2 (en) 2022-08-23
US10787463B2 (en) 2020-09-29
US20210171546A1 (en) 2021-06-10
US20180201626A1 (en) 2018-07-19
IL283355B (en) 2022-08-01
RU2018105752A (ru) 2019-08-21
CA2991326A1 (en) 2017-01-26
AU2023201339A1 (en) 2023-04-06
US9890179B2 (en) 2018-02-13
HK1252321A1 (en) 2019-05-24
EP3653628A1 (en) 2020-05-20
IL294651B1 (en) 2023-10-01
US20190112320A1 (en) 2019-04-18
JP7334228B2 (ja) 2023-08-28
JP2018524387A (ja) 2018-08-30
JP2023162264A (ja) 2023-11-08
KR102660070B1 (ko) 2024-04-24
CY1122553T1 (el) 2021-01-27
RS59806B1 (sr) 2020-02-28
IL286788B1 (en) 2023-09-01
US20170050985A1 (en) 2017-02-23
HUE051541T2 (hu) 2021-03-01
IL276631A (en) 2020-09-30
IL256861B (en) 2020-08-31
IL276630B (en) 2021-06-30
US9873708B2 (en) 2018-01-23
RS60840B1 (sr) 2020-10-30
RU2018105756A3 (OSRAM) 2019-12-23
ES2959741T3 (es) 2024-02-28
WO2017015495A1 (en) 2017-01-26
CA2992082A1 (en) 2017-01-26
SMT202000004T1 (it) 2020-03-13
KR20240055903A (ko) 2024-04-29
AU2021202403A1 (en) 2021-05-20
EP3325482A1 (en) 2018-05-30
CA2991305C (en) 2024-03-12
RU2746322C2 (ru) 2021-04-12
LT3325482T (lt) 2020-11-25
HK1252323A1 (en) 2019-05-24
JP6787995B2 (ja) 2020-11-18
EP3778602A1 (en) 2021-02-17
IL283355A (en) 2021-07-29
AU2021203148A1 (en) 2021-06-10
ES2764548T3 (es) 2020-06-03
KR20180038460A (ko) 2018-04-16
US10081640B2 (en) 2018-09-25
IL256854A (en) 2018-03-29
CN113004288A (zh) 2021-06-22
US20190010169A1 (en) 2019-01-10
AU2021203148B2 (en) 2023-01-12
US10392407B2 (en) 2019-08-27
AU2016297087A1 (en) 2018-02-08
EP3325485B1 (en) 2020-04-08
AU2016297608B2 (en) 2021-02-18
US10370389B2 (en) 2019-08-06
US20200017526A1 (en) 2020-01-16
JP2018526340A (ja) 2018-09-13
US10899775B2 (en) 2021-01-26
EP3778602B1 (en) 2023-07-12
CN108026103A (zh) 2018-05-11
AU2016297087B2 (en) 2021-02-18
CN108026103B (zh) 2021-04-16
KR20180026741A (ko) 2018-03-13
RU2018105609A3 (OSRAM) 2020-04-30
WO2017015502A1 (en) 2017-01-26
DK3325483T3 (da) 2020-01-20
JP2021035958A (ja) 2021-03-04

Similar Documents

Publication Publication Date Title
IL291598A (en) History of benzodiazepine cytotoxicity
IL286788A (en) Methods for the preparation of cytotoxic benzodiazepine compounds
SG11201706729SA (en) Derivatives of sobetirome
HUE056357T2 (hu) Szobetirom származékok
IL287405A (en) Methods for preparing cytotoxic benzodiazepine derivatives
IL293192A (en) Methods for the preparation of indolinobenzodiazepine derivatives
IL283045A (en) Methods for preparing cytotoxic benzodiazepine derivatives
IL283047A (en) Methods for preparing cytotoxic benzodiazepine derivatives
GB201414116D0 (en) Benzodiazepine derivatives
GB201513979D0 (en) Synthesis of benzodiazepine derivatives
HUP1400545A2 (hu) Eljárás benzazepin származékok elõállítására
HK1236934A1 (zh) 细胞毒性苯并二氮呯衍生物