JP6166728B2 - ピロロベンゾジアゼピンの製造に有用な合成方法及び中間体 - Google Patents

ピロロベンゾジアゼピンの製造に有用な合成方法及び中間体 Download PDF

Info

Publication number
JP6166728B2
JP6166728B2 JP2014535096A JP2014535096A JP6166728B2 JP 6166728 B2 JP6166728 B2 JP 6166728B2 JP 2014535096 A JP2014535096 A JP 2014535096A JP 2014535096 A JP2014535096 A JP 2014535096A JP 6166728 B2 JP6166728 B2 JP 6166728B2
Authority
JP
Japan
Prior art keywords
group
compound
formula
mmol
acid
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
JP2014535096A
Other languages
English (en)
Japanese (ja)
Other versions
JP2015502331A (ja
JP2015502331A5 (https=
Inventor
フィリップ・ウィルソン・ハワード
アルノー・ティベルギアン
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
MedImmune Ltd
Original Assignee
MedImmune Ltd
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 MedImmune Ltd filed Critical MedImmune Ltd
Publication of JP2015502331A publication Critical patent/JP2015502331A/ja
Publication of JP2015502331A5 publication Critical patent/JP2015502331A5/ja
Application granted granted Critical
Publication of JP6166728B2 publication Critical patent/JP6166728B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052—Val-amino acid
    • 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
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
JP2014535096A 2011-10-14 2012-10-12 ピロロベンゾジアゼピンの製造に有用な合成方法及び中間体 Active JP6166728B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161547207P 2011-10-14 2011-10-14
US61/547,207 2011-10-14
PCT/EP2012/070232 WO2013053872A1 (en) 2011-10-14 2012-10-12 Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines

Publications (3)

Publication Number Publication Date
JP2015502331A JP2015502331A (ja) 2015-01-22
JP2015502331A5 JP2015502331A5 (https=) 2015-12-03
JP6166728B2 true JP6166728B2 (ja) 2017-07-19

Family

ID=47019019

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2014535096A Active JP6166728B2 (ja) 2011-10-14 2012-10-12 ピロロベンゾジアゼピンの製造に有用な合成方法及び中間体

Country Status (9)

Country Link
US (1) US9102704B2 (https=)
EP (1) EP2751076B1 (https=)
JP (1) JP6166728B2 (https=)
CN (1) CN104011018B (https=)
AU (1) AU2012322933B2 (https=)
BR (1) BR112014009070B1 (https=)
CA (1) CA2850096C (https=)
EA (1) EA029046B1 (https=)
WO (1) WO2013053872A1 (https=)

Families Citing this family (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
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
CA2795349C (en) 2010-04-15 2016-11-29 Seattle Genetics, Inc. Targeted pyrrolobenzodiazepine conjugates
SG11201400770SA (en) 2011-09-20 2014-04-28 Spirogen Sarl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates
AU2012322932B2 (en) 2011-10-14 2016-11-10 Medimmune Limited Pyrrolobenzodiazepines
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
CN103997893B (zh) 2011-10-14 2019-04-12 西雅图基因公司 吡咯并苯并二氮杂卓和靶向结合物
EP2751111B1 (en) 2011-10-14 2017-04-26 MedImmune Limited Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative or autoimmune diseases
ES2680153T3 (es) 2012-10-12 2018-09-04 Adc Therapeutics Sa Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas
JP6392765B2 (ja) 2012-10-12 2018-09-19 エイディーシー・セラピューティクス・エス・アーＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａ ピロロベンゾジアゼピン−抗体結合体
EP2906296B1 (en) 2012-10-12 2018-03-21 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
HRP20190366T1 (hr) 2012-10-12 2019-04-19 Medimmune Limited Pirolobenzodiazepini i njihovi konjugati
RS57694B1 (sr) 2012-10-12 2018-11-30 Adc Therapeutics Sa Pirolobenzodiazepin - anti-psma konjugati antitela
EP2906249B1 (en) 2012-10-12 2018-06-27 MedImmune Limited Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
MX338711B (es) 2012-10-12 2016-04-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
HRP20182129T1 (hr) 2012-10-12 2019-02-08 Adc Therapeutics Sa Konjugati protutijelo - pirolobenzodiazepin
EP2906297B1 (en) 2012-10-12 2017-12-06 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
CN105189507A (zh) 2012-12-21 2015-12-23 斯皮罗根有限公司 吡咯并苯并二氮杂卓及其结合物
CN110627797A (zh) 2012-12-21 2019-12-31 麦迪穆有限责任公司 用于治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物
AU2014229529B2 (en) 2013-03-13 2018-02-15 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
TWI680766B (zh) 2013-03-13 2020-01-01 英商梅迪繆思有限公司 吡咯并苯并二氮呯及其共軛物
JP6847388B2 (ja) 2013-03-15 2021-03-31 レゲネロン ファーマシューティカルス，インコーポレーテッド 生物活性分子、そのコンジュゲート、及び治療用途
BR112016004023A2 (pt) 2013-08-26 2022-11-16 Regeneron Pharma Composição, métodos para preparar uma composição e para tratar uma doença, e, composto
WO2015052534A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
WO2015052535A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
EP3054983B1 (en) 2013-10-11 2019-03-20 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
JP6632984B2 (ja) 2014-03-11 2020-01-22 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 抗ＥＧＦＲｖＩＩＩ抗体およびその使用
EP3193940A1 (en) 2014-09-10 2017-07-26 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
GB201416112D0 (en) 2014-09-12 2014-10-29 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
CN107148285B (zh) 2014-11-25 2022-01-04 Adc治疗股份有限公司 吡咯并苯并二氮杂䓬-抗体缀合物
BR112017020149A8 (pt) 2015-03-27 2023-05-02 Regeneron Pharma Derivados de maitansinoide, conjugados dos mesmos e métodos de uso
GB201506402D0 (en) 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506411D0 (en) 2015-04-15 2015-05-27 Bergenbio As Humanized anti-axl antibodies
IL296285A (en) 2015-07-06 2022-11-01 Regeneron Pharma Multispecific antigen-binding molecules and uses thereof
MA43416A (fr) 2015-12-11 2018-10-17 Regeneron Pharma Méthodes pour ralentir ou empêcher la croissance de tumeurs résistantes au blocage de l'egfr et/ou d'erbb3
BR112018014759B1 (pt) 2016-01-25 2024-02-27 Regeneron Pharmaceuticals, Inc Compostos derivados de maitasinoide e seus conjugados, composição compreendendo os mesmos, seus métodos de fabricação e uso
GB201601431D0 (en) 2016-01-26 2016-03-09 Medimmune Ltd Pyrrolobenzodiazepines
GB201602356D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
GB201602359D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
EP3448891A1 (en) 2016-04-28 2019-03-06 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
EP3478324A1 (en) 2016-07-01 2019-05-08 GlaxoSmithKline Intellectual Property (No.2) Limited Antibody-drug conjugates and therapeutic methods using the same
JP7066690B2 (ja) 2016-09-23 2022-05-13 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 抗ｍｕｃ１６（ムチン１６）抗体
MY199468A (en) 2016-09-23 2023-10-31 Regeneron Pharma Anti-steap2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind steap2 and cd3, and uses thereof
GB201617466D0 (en) 2016-10-14 2016-11-30 Medimmune Ltd Pyrrolobenzodiazepine conjugates
ES3046537T3 (en) 2016-11-08 2025-12-02 Regeneron Pharma Steroids and protein-conjugates thereof
TWI782930B (zh) 2016-11-16 2022-11-11 美商再生元醫藥公司 抗ｍｅｔ抗體，結合ｍｅｔ之雙特異性抗原結合分子及其使用方法
RS61795B1 (sr) 2017-02-08 2021-06-30 Adc Therapeutics Sa Konjugati pirolobenzodiazepin antitela
GB201702031D0 (en) 2017-02-08 2017-03-22 Medlmmune Ltd Pyrrolobenzodiazepine-antibody conjugates
CN110582505B (zh) 2017-04-18 2021-04-02 免疫医疗有限公司 吡咯并苯并二氮杂*缀合物
WO2018193102A1 (en) 2017-04-20 2018-10-25 Adc Therapeutics Sa Combination therapy with an anti-axl antibody-drug conjugate
WO2018213082A1 (en) 2017-05-18 2018-11-22 Regeneron Pharmaceuticals, Inc. Bis-octahydrophenanthrene carboxamides and protein conjugates thereof
KR20200007905A (ko) 2017-05-18 2020-01-22 리제너론 파마슈티칼스 인코포레이티드 사이클로덱스트린 단백질 약물 접합체
DK3635009T3 (da) 2017-06-07 2026-03-30 Regeneron Pharma Sammensætninger og fremgangsmåder til internalisering af enzymer
CA3064804A1 (en) 2017-06-14 2018-12-20 Adc Therapeutics Sa Dosage regimes for the administration of an anti-cd19 adc
KR102270107B1 (ko) 2017-08-18 2021-06-30 메디뮨 리미티드 피롤로벤조디아제핀 컨쥬게이트
NZ762505A (en) 2017-09-29 2026-03-27 Daiichi Sankyo Co Ltd Antibody-pyrrolobenzodiazepine derivative conjugate
MX2020004691A (es) 2017-11-07 2020-08-20 Regeneron Pharma Enlazadores hidrofilicos para conjugados anticuerpo-farmaco.
SG11202006510XA (en) 2018-01-08 2020-08-28 Regeneron Pharma Steroids and antibody-conjugates thereof
GB201803342D0 (en) 2018-03-01 2018-04-18 Medimmune Ltd Methods
EP3774923A4 (en) 2018-03-28 2021-12-29 Mitsubishi Tanabe Pharma Corporation Drug conjugates of cmet monoclonal binding agents, and uses thereof
GB201806022D0 (en) 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
KR102871690B1 (ko) 2018-04-30 2025-10-16 리제너론 파마슈티칼스 인코포레이티드 Her2 및/또는 aplp2에 결합하는 항체 및 이중특이적 항원-결합 분자 및 접합체 그리고 이들의 용도
CN118955710A (zh) 2018-05-09 2024-11-15 里珍纳龙药品有限公司 抗msr1抗体及其使用方法
BR112020023145A2 (pt) 2018-05-17 2021-02-02 Regeneron Pharmaceuticals, Inc. anticorpo anti-cd63 ou fragmento de ligação ao antígeno do mesmo, molécula de ligação ao antígeno biespecífica, proteína terapêutica de múltiplos domínios, polinucleotídeo composição farmacêutica, e, composto
IL283313B2 (en) 2018-11-20 2025-08-01 Regeneron Pharma Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof for use as lxr agonists
PH12021551476A1 (en) 2018-12-21 2022-04-25 Regeneron Pharma Rifamycin analogs and antibody-drug conjugates thereof
JP7590328B2 (ja) 2018-12-21 2024-11-26 レゲネロン ファーマシューティカルス，インコーポレーテッド ツブリシン及びタンパク質－ツブリシンコンジュゲート
BR112021013464A2 (pt) 2019-01-08 2021-09-21 Regeneron Pharmaceuticals, Inc. Ligantes sem traço e conjugados de proteína dos mesmos
CA3128519A1 (en) 2019-02-21 2020-08-27 Regeneron Pharmaceuticals, Inc. Methods of treating ocular cancer using anti-met antibodies and bispecific antigen binding molecules that bind met
CN113631560B (zh) 2019-03-15 2025-02-18 麦迪穆有限责任公司 氮杂环丁烷并苯并二氮杂䓬二聚体和用于治疗癌症的包含它们的缀合物
AU2020349462A1 (en) 2019-09-16 2022-03-03 Regeneron Pharmaceuticals, Inc. Radiolabeled MET binding proteins for immuno-PET imaging
US11814428B2 (en) 2019-09-19 2023-11-14 Regeneron Pharmaceuticals, Inc. Anti-PTCRA antibody-drug conjugates and uses thereof
JP2023511956A (ja) 2020-01-24 2023-03-23 レゲネロン ファーマシューティカルス，インコーポレーテッド タンパク質－抗ウイルス化合物コンジュゲート
KR20220148200A (ko) 2020-02-28 2022-11-04 리제너론 파마슈티칼스 인코포레이티드 Her2에 결합하는 이중특이적 항원 결합 분자 및 이의 사용 방법
CN115968304A (zh) 2020-04-16 2023-04-14 瑞泽恩制药公司 狄尔斯-阿尔德缀合方法
WO2021262910A2 (en) 2020-06-24 2021-12-30 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
CN116390771A (zh) 2020-07-13 2023-07-04 瑞泽恩制药公司 与蛋白中的谷氨酰胺残基缀合的喜树碱类似物及其用途
CA3191304A1 (en) 2020-09-14 2022-03-17 Amy Han Antibody-drug conjugates comprising glp1 peptidomimetics and uses thereof
CA3190569A1 (en) 2020-10-22 2022-04-28 Christopher Daly Anti-fgfr2 antibodies and methods of use thereof
CA3220081A1 (en) 2021-07-28 2023-02-02 Thomas Nittoli Protein-antiviral compound conjugates
AU2022353890A1 (en) 2021-09-30 2024-04-04 Jiangsu Hengrui Pharmaceuticals Co., Ltd. Pyrrolo benzodiazepine derivative, and conjugate, preparation method and use thereof
US20230414775A1 (en) 2021-12-29 2023-12-28 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
CA3241734A1 (en) 2022-01-12 2023-07-20 Amy Han Camptothecin analogs conjugated to a glutamine residue in a protein, and their use
AU2023208050A1 (en) 2022-01-14 2024-07-04 Regeneron Pharmaceuticals, Inc. Verrucarin a derivatives and antibody drug conjugates thereof
JP2025512735A (ja) 2022-03-11 2025-04-22 リジェネロン ファーマシューティカルズ，インク． Ｇｌｐ１ペプチド模倣体を含む抗ｇｌｐ１ｒ抗体係留型薬物コンジュゲートおよびその使用
EP4548932A1 (en) 2022-06-30 2025-05-07 Toray Industries, Inc. Pharmaceutical composition for treating and/or preventing cancer
CN120239705A (zh) 2022-07-21 2025-07-01 萤火虫生物股份有限公司 糖皮质激素受体激动剂和其缀合物
WO2024118785A2 (en) 2022-11-30 2024-06-06 Regeneron Pharmaceuticals, Inc. Tlr7 agonists and antibody-drug-conjugates thereof
WO2024138000A1 (en) 2022-12-21 2024-06-27 Regeneron Pharmaceuticals, Inc. Prodrugs of topoisomerase i inhibitor for adc conjugations and methods of use thereof
WO2024168199A1 (en) 2023-02-09 2024-08-15 Regeneron Pharmaceuticals, Inc. Antibody-drug conjugates via inverse electron demand diels-alder reactions
WO2024229105A1 (en) 2023-05-02 2024-11-07 Regeneron Pharmaceuticals, Inc. Anti-human m-cadherin (cdh15) antibodies, conjugates, and uses thereof for delivery of genetic payloads to muscle cells
CN121568720A (zh) 2023-07-10 2026-02-24 瑞泽恩制药公司 抗人类cacng1抗体-药物缀合物及其用途
US20250171516A1 (en) 2023-11-03 2025-05-29 Regeneron Pharmaceuticals, Inc. Peptide acids as a glp1r agonist and antibody-drug conjugates thereof
WO2025117727A1 (en) 2023-11-29 2025-06-05 Regeneron Pharmaceuticals, Inc. Analogs of quinoxaline/quinoline cytotoxins, linker- payloads, protein-drug conjugates, and uses thereof
US20260078179A1 (en) 2024-07-18 2026-03-19 Novarock Biotherapeutics, Ltd. Cdh17 antibodies and uses thereof

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3523941A (en) 1967-03-06 1970-08-11 Hoffmann La Roche Benzodiazepine compounds and process for their preparation
US3524849A (en) 1967-10-27 1970-08-18 Hoffmann La Roche Process for the preparation of pyrrolo-benzodiazepine acrylamides and intermediates useful therein
US3619374A (en) 1967-12-04 1971-11-09 Hoffmann La Roche Antibiotic production utilizing streptomyces refuineus var. thermotolerans
IL33558A (en) 1968-12-30 1973-10-25 Fujisawa Pharmaceutical Co Antibiotic pyrrolo-benzodiazepine compound,its derivatives and processes for their production
DE1965304A1 (de) 1968-12-30 1970-07-23 Fujisawa Pharmaceutical Co Benzdiazepinon-Verbindungen und Verfahren zu ihrer Herstellung
JPS6053033B2 (ja) 1976-12-28 1985-11-22 財団法人微生物化学研究会 新制癌抗生物質マゼスラマイシン及びその製造方法
JPS585916B2 (ja) 1977-12-27 1983-02-02 株式会社ミドリ十字 新規ベンゾジアゼピン系化合物
JPS5615289A (en) 1979-07-17 1981-02-14 Green Cross Corp:The Novel benzodiazepinnbased compound 3
JPS57131791A (en) 1980-12-31 1982-08-14 Fujisawa Pharmaceut Co Ltd Benzodiazepine derivative and its preparation
JPS58180487A (ja) 1982-04-16 1983-10-21 Kyowa Hakko Kogyo Co Ltd 抗生物質ｄｃ−８１およびその製造法
FR2586683B1 (fr) 1985-08-29 1988-07-01 Centre Nat Rech Scient Nouveaux derives de neothramycine, leur procede de preparation et leur application en tant que medicaments
FR2676230B1 (fr) 1991-05-07 1993-08-27 Centre Nat Rech Scient Nouveaux derives de pyrrolo [1,4]-benzodiazepines, leur procede de preparation et medicaments les contenant.
GB9205051D0 (en) 1992-03-09 1992-04-22 Cancer Res Campaign Tech Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them
FR2696176B1 (fr) 1992-09-28 1994-11-10 Synthelabo Dérivés de pipéridine, leur préparation et leur application en thérapeutique.
GB9818730D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collections of compounds
GB9818732D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collection of compounds
DE69925133T2 (de) 1998-08-27 2006-01-19 Spirogen Ltd., Ryde Pyrrolobenzodiazepine
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
US6909006B1 (en) 1999-08-27 2005-06-21 Spirogen Limited Cyclopropylindole derivatives
US6660856B2 (en) 2002-03-08 2003-12-09 Kaohsiung Medical University Synthesis of pyrrolo[2,1-c][1,4]benzodiazepine analogues
US20040138269A1 (en) 2002-10-11 2004-07-15 Sugen, Inc. Substituted pyrroles as kinase inhibitors
GB0226593D0 (en) * 2002-11-14 2002-12-24 Consultants Ltd Compounds
GB0321295D0 (en) * 2003-09-11 2003-10-15 Spirogen Ltd Synthesis of protected pyrrolobenzodiazepines
GB0416511D0 (en) 2003-10-22 2004-08-25 Spirogen Ltd Pyrrolobenzodiazepines
WO2005040170A2 (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
WO2005085251A1 (en) * 2004-03-01 2005-09-15 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
GB0404577D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
GB0404574D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Amino acids
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
WO2005085260A1 (en) 2004-03-09 2005-09-15 Spirogen Limited Pyrrolobenzodiazepines
GB0410725D0 (en) 2004-05-13 2004-06-16 Spirogen Ltd Pyrrolobenzodiazepine therapeutic agents
US7612062B2 (en) 2005-04-21 2009-11-03 Spirogen Limited Pyrrolobenzodiazepines
US8637664B2 (en) 2005-10-05 2014-01-28 Spirogen Sarl Alkyl 4- [4- (5-oxo-2,3,5, 11a-tetrahydo-5H-pyrrolo [2, 1-c] [1,4] benzodiazepine-8-yloxy)-butyrylamino]-1H-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease
JP2008050321A (ja) 2006-08-28 2008-03-06 Univ Kanagawa 光分解性カップリング剤
GB0813432D0 (en) 2008-07-22 2008-08-27 Spirogen Ltd Pyrrolobenzodiazepines
GB0819095D0 (en) * 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
GB201006340D0 (en) 2010-04-15 2010-06-02 Spirogen Ltd Synthesis method and intermediates

Also Published As

Publication number Publication date
EA201490550A1 (ru) 2014-09-30
EA029046B1 (ru) 2018-02-28
EP2751076A1 (en) 2014-07-09
BR112014009070A2 (pt) 2017-04-18
JP2015502331A (ja) 2015-01-22
BR112014009070B1 (pt) 2021-11-23
AU2012322933B2 (en) 2017-02-02
CN104011018A (zh) 2014-08-27
WO2013053872A1 (en) 2013-04-18
EP2751076B1 (en) 2018-04-25
AU2012322933A1 (en) 2014-05-29
CN104011018B (zh) 2016-12-14
US9102704B2 (en) 2015-08-11
US20140275522A1 (en) 2014-09-18
CA2850096A1 (en) 2013-04-18
CA2850096C (en) 2018-07-03

Similar Documents

Publication Publication Date Title
JP6166728B2 (ja) ピロロベンゾジアゼピンの製造に有用な合成方法及び中間体
JP6063862B2 (ja) ピロロベンゾジアゼピンの合成に有用な中間体
JP4909258B2 (ja) Ｃ２置換ピロロベンゾジアゼピン類を調製するための主要な中間体としての１１−ヒドロキシ−５Ｈ−ピロロ［２，１−ｃ］［１，４］ベンゾジアゼピン−５−オン誘導体
CA2885305C (en) Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
CA2735477C (en) Unsymmetrical pyrrolobenzodiazepine-dimers for treatment of proliferative diseases
JP5669740B2 (ja) ピロロベンゾジアゼピン
EP1879901B1 (en) Pyrrolobenzodiazepines
HK1195072B (en) Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines
HK1195072A (en) Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20151013

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20151013

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20160512

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20160616

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20160621

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20160921

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20161121

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20161220

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20170420

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20170501

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20170530

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20170623

R150 Certificate of patent or registration of utility model

Ref document number: 6166728

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250