CY1123390T1 - Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινων - Google Patents

Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινων

Info

Publication number
CY1123390T1
CY1123390T1 CY20201100899T CY201100899T CY1123390T1 CY 1123390 T1 CY1123390 T1 CY 1123390T1 CY 20201100899 T CY20201100899 T CY 20201100899T CY 201100899 T CY201100899 T CY 201100899T CY 1123390 T1 CY1123390 T1 CY 1123390T1
Authority
CY
Cyprus
Prior art keywords
preparation
methods
benzodiazepine derivatives
cytotoxic benzodiazepine
cytotoxic
Prior art date
Application number
CY20201100899T
Other languages
English (en)
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 CY1123390T1 publication Critical patent/CY1123390T1/el

Links

Classifications

    • 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
    • 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
    • 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
    • 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
    • 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)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (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)
  • 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)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pyridine Compounds (AREA)

Abstract

Η εφεύρεση σχετίζεται με καινοφανείς μεθόδους για παρασκευή ενώσεων διμερών ινδολινοβενζοδιαζεπινών και των συνθετικών πρόδρομων αυτών.
CY20201100899T 2015-07-21 2020-09-23 Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινων CY1123390T1 (el)

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
CY1123390T1 true CY1123390T1 (el) 2022-03-24

Family

ID=56557925

Family Applications (2)

Application Number Title Priority Date Filing Date
CY20191101364T CY1122553T1 (el) 2015-07-21 2019-12-30 Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινης
CY20201100899T CY1123390T1 (el) 2015-07-21 2020-09-23 Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινων

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CY20191101364T CY1122553T1 (el) 2015-07-21 2019-12-30 Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινης

Country Status (22)

Country Link
US (11) US10081640B2 (el)
EP (7) EP3325483B1 (el)
JP (8) JP6858745B2 (el)
KR (5) KR102660070B1 (el)
CN (5) CN113087763A (el)
AU (7) AU2016297087B2 (el)
CA (4) CA2991305C (el)
CY (2) CY1122553T1 (el)
DK (2) DK3325483T3 (el)
ES (4) ES2933376T3 (el)
HK (3) HK1252321A1 (el)
HR (1) HRP20201479T1 (el)
HU (1) HUE051541T2 (el)
IL (10) IL283355B (el)
LT (2) LT3325483T (el)
PL (2) PL3325482T3 (el)
PT (2) PT3325483T (el)
RS (2) RS59806B1 (el)
RU (3) RU2018105752A (el)
SG (2) SG10202009354SA (el)
SI (2) SI3325482T1 (el)
WO (3) WO2017015502A1 (el)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102660070B1 (ko) * 2015-07-21 2024-04-24 이뮤노젠 아이엔씨 세포독성 벤조다이아제핀 유도체의 제조 방법
CN118098939A (zh) 2016-03-22 2024-05-28 Ev 集团 E·索尔纳有限责任公司 用于衬底的接合的装置和方法
AU2017345454A1 (en) 2016-10-19 2019-05-30 Invenra Inc. Antibody constructs
EA201991204A1 (ru) 2016-12-22 2019-12-30 Университа Дельи Студи Манья Греча Катандзаро Моноклональное антитело против уникального сиалогликозилированного опухолеассоциированного эпитопа cd43
PT3573948T (pt) 2017-01-25 2023-01-11 Immunogen Inc Métodos de preparação de derivados de benzodiazepina citotóxicos
EP3802580A1 (en) 2018-06-05 2021-04-14 King's College London Btnl3/8 targeting constructs for delivery of payloads to the gastrointestinal system
CN118324848A (zh) * 2018-11-12 2024-07-12 伊缪诺金公司 制备细胞毒性苯并二氮杂卓衍生物的方法
AU2019381628A1 (en) * 2018-11-12 2021-05-27 Immunogen, Inc. Methods of preparing cytotoxic benzodiazepine derivatives
JP2022529583A (ja) * 2019-03-29 2022-06-23 イミュノジェン・インコーポレーテッド 異常細胞増殖を阻害するまたは増殖性疾患を治療するための細胞毒性ビス－ベンゾジアゼピン誘導体及び細胞結合剤とのその複合体

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
EP0563475B1 (en) 1992-03-25 2000-05-31 Immunogen Inc Cell binding agent conjugates of derivatives of CC-1065
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
PT1413582E (pt) 1998-08-27 2006-07-31 Spirogen Ltd Pirrolobenzodiazepinas dimericas
ES2276708T3 (es) 1999-11-24 2007-07-01 Immunogen, Inc. Agentes citotoxicos que comprenden taxanos y su uso terapeutico.
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
WO2004013093A2 (en) 2002-08-02 2004-02-12 Immunogen, Inc. Cytotoxic agents containing novel potent taxanes and their therapeutic use
AU2003259163B2 (en) 2002-08-16 2008-07-03 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
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
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
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
DE60326060D1 (de) 2003-03-31 2009-03-19 Council Scient Ind Res Nichtvernetzende pyrroloä2,1-cüä1,4übenzodiazepine als potentielle antitumor-agentien und ihre herstellung
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
GB2424883B (en) 2003-12-31 2008-10-22 Council Scient Ind Res Process for preparing pyrrolo[2, 1-c] [1,4] benzodiazepine hybrids
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
SI1720881T1 (sl) * 2004-03-01 2013-04-30 Spirogen Sarl 11-hidroksi-5H-pirolo(2,1-c)(1,4)benzodiazepin-5onski derivati kot ključni intermediati za pipravo C2 substituiranih pirolobenzodiazepinov
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
NZ563136A (en) 2005-04-21 2009-11-27 Spirogen Ltd Pyrrolobenzodiazepines
WO2007039752A1 (en) 2005-10-05 2007-04-12 Spirogen Limited Alkyl 4- [4- (5-oxo-2, 3, 5, 11a-tetrahyd0-5h-pyrr0l0 [2, 1-c] [1, 4] benzodiazepine-8-yloxy) -butyrylamino]-1h-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease
CN102702194A (zh) * 2005-12-21 2012-10-03 雅培制药有限公司 抗病毒化合物
ATE527262T1 (de) 2006-01-25 2011-10-15 Sanofi Sa Neue tomaymycin derivate enhaltende zytotoxische mittel
GB2453402B (en) 2006-02-13 2010-12-22 Council Scient Ind Res Novel bis-pyrrolo[2,1.-c] [1,4] benzodiazepine-anthraquinone conjugates and a process for the preparation thereof
MX2008015132A (es) 2006-05-30 2008-12-10 Genentech Inc Anticuerpos e inmunoconjugados y sus usos.
ES2435779T3 (es) 2007-07-19 2013-12-23 Sanofi Agentes citotóxicos que comprenden nuevos derivados de tomaimicina y su uso terapéutico
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
KR20100137585A (ko) 2008-04-30 2010-12-30 이뮤노젠 아이엔씨 강력한 복합체 및 친수성 링커
KR20220035504A (ko) 2008-04-30 2022-03-22 이뮤노젠 아이엔씨 가교제 및 그 용도
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
GB0822260D0 (en) * 2008-12-05 2009-01-14 Merten Christoph Assay
US8637558B2 (en) * 2008-12-30 2014-01-28 Industry-Academic Cooperation Foundation, Chosun University Thiazolidinedione derivative and use thereof
IL271761B (en) 2009-02-05 2022-09-01 Immunogen Inc (12as)-8-methoxy-9-benzyloxy-11,12,12a,13-tetrahydro-6h-indolo[2,1-c][1,4]benzodiazepine-6-one, 4-benzyloxy-5-methoxy -2-nitrobenzoic acid and a process for their preparation
EP2486023A4 (en) 2009-10-06 2014-05-07 Immunogen Inc EFFICIENT CONJUGATES AND HYDROPHILIC BINDER
US8314250B2 (en) * 2009-11-24 2012-11-20 Hoffmann-La Roche Inc. Sultam derivatives
CN102666480B (zh) 2009-12-08 2014-04-09 国立大学法人岐阜大学 芳香族化合物、低聚核苷酸衍生物合成用修饰载体、低聚核苷酸衍生物及低聚核苷酸构建物
US8962279B2 (en) * 2009-12-30 2015-02-24 Intel Corporation Solid-phase chelators and electronic biosensors
NZ717149A (en) * 2010-02-11 2017-06-30 Celgene Corp Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same for treating various diseases
CN103037900B (zh) 2010-02-24 2016-04-06 伊缪诺金公司 叶酸受体1抗体与免疫缀合物以及其用途
AU2011239522B2 (en) 2010-04-15 2014-10-23 Medimmune Limited Targeted pyrrolobenzodiazapine conjugates
AU2011239525B2 (en) 2010-04-15 2015-04-09 Medimmune Limited Pyrrolobenzodiazepines used to treat proliferative diseases
PE20130342A1 (es) 2010-04-15 2013-04-20 Spirogen Sarl Pirrolobenzodiacepinas y conjugados de las mismas
US9534000B2 (en) * 2011-02-15 2017-01-03 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
WO2014031566A1 (en) * 2012-08-22 2014-02-27 Immunogen, Inc. Cytotoxic benzodiazepine derivatives
JP6694811B2 (ja) * 2013-10-04 2020-05-20 ノバルティス アーゲー ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ
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
CA2957964A1 (en) 2014-09-03 2016-03-10 Immunogen, Inc. Conjugates comprising cell-binding agents and cytotoxic agents
PL3189056T3 (pl) 2014-09-03 2020-11-02 Immunogen, Inc. Cytotoksyczne pochodne benzodiazepinowe
JP2017527562A (ja) 2014-09-03 2017-09-21 イミュノジェン・インコーポレーテッド 細胞毒性ベンゾジアゼピン誘導体
KR102660070B1 (ko) * 2015-07-21 2024-04-24 이뮤노젠 아이엔씨 세포독성 벤조다이아제핀 유도체의 제조 방법
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
SI3325482T1 (sl) 2020-11-30
EP3325482A1 (en) 2018-05-30
AU2016297087A1 (en) 2018-02-08
IL276631B (en) 2021-10-31
PL3325483T3 (pl) 2020-05-18
US20210171546A1 (en) 2021-06-10
JP7334228B2 (ja) 2023-08-28
US10899775B2 (en) 2021-01-26
JP2018524387A (ja) 2018-08-30
AU2016297608B2 (en) 2021-02-18
IL286788B1 (en) 2023-09-01
RU2746322C2 (ru) 2021-04-12
JP2018522018A (ja) 2018-08-09
LT3325483T (lt) 2020-01-27
WO2017015502A1 (en) 2017-01-26
IL286788A (en) 2021-10-31
ES2959741T3 (es) 2024-02-28
EP4286387A2 (en) 2023-12-06
AU2021202403A1 (en) 2021-05-20
RS59806B1 (sr) 2020-02-28
CA2991305A1 (en) 2017-01-26
KR20180026741A (ko) 2018-03-13
PL3325482T3 (pl) 2021-01-11
CN113004288A (zh) 2021-06-22
US11420982B2 (en) 2022-08-23
CA2992082A1 (en) 2017-01-26
EP3653628A1 (en) 2020-05-20
US20170050985A1 (en) 2017-02-23
AU2021202403B2 (en) 2022-12-08
US20230257400A1 (en) 2023-08-17
IL305989A (en) 2023-11-01
KR20180038460A (ko) 2018-04-16
US20170050986A1 (en) 2017-02-23
EP3325483B1 (en) 2019-10-02
EP3325485A1 (en) 2018-05-30
US10787463B2 (en) 2020-09-29
ES2820358T3 (es) 2021-04-20
US20190389883A1 (en) 2019-12-26
KR102660070B1 (ko) 2024-04-24
DK3325483T3 (da) 2020-01-20
IL283355A (en) 2021-07-29
AU2016297087B2 (en) 2021-02-18
WO2017015496A1 (en) 2017-01-26
US20170051011A1 (en) 2017-02-23
ES2764548T3 (es) 2020-06-03
AU2023202221A1 (en) 2023-05-04
HK1252321A1 (zh) 2019-05-24
EP3325485B1 (en) 2020-04-08
EP3325483A1 (en) 2018-05-30
CN108055844A (zh) 2018-05-18
RU2018105756A3 (el) 2019-12-23
IL294651B2 (en) 2024-02-01
IL256854A (en) 2018-03-29
IL256861A (en) 2018-03-29
SI3325483T1 (sl) 2020-03-31
CN108026103A (zh) 2018-05-11
RU2018105752A (ru) 2019-08-21
AU2023201339A1 (en) 2023-04-06
EP4163284A1 (en) 2023-04-12
HK1252323A1 (zh) 2019-05-24
RU2018105756A (ru) 2019-08-21
HK1252322A1 (zh) 2019-05-24
EP3325482B1 (en) 2020-06-24
HRP20201479T1 (hr) 2020-12-11
JP2022046542A (ja) 2022-03-23
EP3778602A1 (en) 2021-02-17
US9890179B2 (en) 2018-02-13
HUE051541T2 (hu) 2021-03-01
US20190010169A1 (en) 2019-01-10
JP2021035958A (ja) 2021-03-04
EP3653628B1 (en) 2022-09-14
RU2727151C2 (ru) 2020-07-21
KR20240055903A (ko) 2024-04-29
US10081640B2 (en) 2018-09-25
CN108290895B (zh) 2021-03-19
CY1122553T1 (el) 2021-01-27
IL276630B (en) 2021-06-30
US20200017526A1 (en) 2020-01-16
DK3325482T3 (da) 2020-09-28
SG10202009354SA (en) 2020-11-27
US20190112320A1 (en) 2019-04-18
KR102659706B1 (ko) 2024-04-23
CA3227588A1 (en) 2017-01-26
RU2018105609A3 (el) 2020-04-30
JP6858745B2 (ja) 2021-04-14
JP2023162264A (ja) 2023-11-08
WO2017015502A8 (en) 2017-03-02
RU2018105752A3 (el) 2019-12-30
US20210171547A1 (en) 2021-06-10
AU2016297607A1 (en) 2018-02-08
PT3325483T (pt) 2020-01-15
JP2023166434A (ja) 2023-11-21
AU2016297608A1 (en) 2018-02-08
JP6995178B2 (ja) 2022-02-21
CN108290895A (zh) 2018-07-17
AU2021203148A1 (en) 2021-06-10
IL294651B1 (en) 2023-10-01
RS60840B1 (sr) 2020-10-30
KR20240055894A (ko) 2024-04-29
US10370389B2 (en) 2019-08-06
JP7337114B2 (ja) 2023-09-01
CA2991305C (en) 2024-03-12
IL256861B (en) 2020-08-31
KR20180038461A (ko) 2018-04-16
CN108026103B (zh) 2021-04-16
IL276630A (en) 2020-09-30
US9873708B2 (en) 2018-01-23
JP2018526340A (ja) 2018-09-13
IL276631A (en) 2020-09-30
IL256860A (en) 2018-03-29
IL305279A (en) 2023-10-01
EP4286387A3 (en) 2024-02-21
IL294651A (en) 2022-09-01
RU2018105609A (ru) 2019-08-26
WO2017015495A1 (en) 2017-01-26
IL256860B (en) 2020-08-31
AU2021203148B2 (en) 2023-01-12
SG10202106529XA (en) 2021-07-29
CA2991326A1 (en) 2017-01-26
US20180201626A1 (en) 2018-07-19
US10392407B2 (en) 2019-08-27
IL283355B (en) 2022-08-01
CN113087763A (zh) 2021-07-09
IL286788B2 (en) 2024-01-01
LT3325482T (lt) 2020-11-25
JP2021100959A (ja) 2021-07-08
EP3778602B1 (en) 2023-07-12
ES2933376T3 (es) 2023-02-06
JP6787995B2 (ja) 2020-11-18
PT3325482T (pt) 2020-09-24

Similar Documents

Publication Publication Date Title
CY1123390T1 (el) Μεθοδοι παρασκευης κυτταροτοξικων παραγωγων βενζοδιαζεπινων
CY1124004T1 (el) Υποδορια σκευασματα αντισωματων αντι-cd38 και οι χρησεις τους
CY1124886T1 (el) Χιμαιρικοι υποδοχεις αντιγονου bcma
CY1124619T1 (el) Αντισωματα αντι-προ/λανθανουσας μυοστατινης και χρησεις αυτων
CY1122721T1 (el) Αντισωματα που δεσμευουν αχl
CY1121182T1 (el) Συνθεσεις χρησιμες για τη θεραπεια διαταραχων που σχετιζονται με kit
CY1120373T1 (el) Συνθεσεις που περιλαμβανουν βακτηριακα στελεχη
UY37870A (es) Inhibidores de kras g12c y métodos para utilizarlos campo de la invención
CY1124215T1 (el) Μκ2 αναστολεις και χρησεις αυτων
CL2016001871A1 (es) Anticuerpos humanos para pd-1
CY1119489T1 (el) Υποκατεστημενη πιπεριδυλο-αιθυλο-πυριμιδινη ως αναστολεας της ο-ακυλο τρανσφερασης της γκρελινης
CY1124809T1 (el) Διαστεροεπιλεκτικη συνθεση φωσφορικων παραγωγων και προφαρμακου γεμσιταβινης nuc-1031
CY1123920T1 (el) Αντιγριπικο πολυκυκλικο παραγωγο πυριδονης και προφαρμακο αυτου
CR20150524A (es) Compuestos de heteroarilo y sus usos
CY1121602T1 (el) Συνθεση της κοπανλισιμπης και του διυδροχλωρικου αλατος της
MA54254A (fr) Dérivés de benzodiazépine cytotoxique
CY1124425T1 (el) Συνθεσεις οι οποιες περιλαμβανουν συζευγματα φαρμακου αντισωματος-δουοκαρμυκινης
EA201591728A1 (ru) Гетероциклические соединения и способы их применения
CY1123465T1 (el) Αντιβακτηριακες ενωσεις ευρεως φασματος
EA201791454A1 (ru) Лекарственные формы для трансдермального введения
CY1120759T1 (el) Παρασκευη διγλυκοζιτη (s,s)-σεκοϊσολαρικιρεσινολης και διγλυκοζιτη (r,r)-σεκοϊσολαρικιρεσινολης
CL2018000371A1 (es) Complejos de anillos macrocíclicos de pentaaza que poseen biodisponibilidad oral.
CY1123019T1 (el) Σπειροκυκλικες ενωσεις
CY1122287T1 (el) Ενωσεις χρησιμες για την αναστολη toy ror-γαμμα-τ
CY1121171T1 (el) Πυρογλουταμικη βορτιοξετινη