CN104011018B - 可用于制备吡咯并苯并二氮杂卓的合成方法和中间体 - Google Patents

可用于制备吡咯并苯并二氮杂卓的合成方法和中间体 Download PDF

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CN104011018B
CN104011018B CN201280061966.5A CN201280061966A CN104011018B CN 104011018 B CN104011018 B CN 104011018B CN 201280061966 A CN201280061966 A CN 201280061966A CN 104011018 B CN104011018 B CN 104011018B
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CN104011018A (zh
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菲利普·威尔逊·霍华德
阿诺·蒂贝尔吉恩
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MedImmune Ltd
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ADC Therapeutics SA
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    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052Val-amino acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07D207/02Heterocyclic 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
    • C07D207/18Heterocyclic 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
    • C07D207/20Heterocyclic 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
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    • C07D207/22Heterocyclic 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
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/18Heterocyclic 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
    • C07D207/22Heterocyclic 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
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    • C07D207/262-Pyrrolidones
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    • YGENERAL 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
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    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
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  • Medicinal Chemistry (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CN201280061966.5A 2011-10-14 2012-10-12 可用于制备吡咯并苯并二氮杂卓的合成方法和中间体 Active CN104011018B (zh)

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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

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CN104011018B true CN104011018B (zh) 2016-12-14

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US (1) US9102704B2 (enExample)
EP (1) EP2751076B1 (enExample)
JP (1) JP6166728B2 (enExample)
CN (1) CN104011018B (enExample)
AU (1) AU2012322933B2 (enExample)
BR (1) BR112014009070B1 (enExample)
CA (1) CA2850096C (enExample)
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Families Citing this family (97)

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Publication number Priority date Publication date Assignee Title
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
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
CN103987718A (zh) 2011-09-20 2014-08-13 斯皮罗根有限公司 作为非对称二聚体pbd化合物用于内含在靶向结合物中的吡咯并苯并二氮杂卓
CA2850375C (en) 2011-10-14 2019-07-02 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
US9388187B2 (en) 2011-10-14 2016-07-12 Medimmune Limited Pyrrolobenzodiazepines
JP6393617B2 (ja) 2011-10-14 2018-09-19 シアトル ジェネティクス,インコーポレーテッド ピロロベンゾジアゼピンおよび標的コンジュゲート
CA2850103C (en) 2011-10-14 2019-09-10 Spirogen Sarl Pyrrolobenzodiazepines
CA2885305C (en) 2012-10-12 2019-11-12 Spirogen Sarl Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
JP6270859B2 (ja) 2012-10-12 2018-01-31 エイディーシー・セラピューティクス・エス・アー・エール・エルAdc Therapeutics Sarl ピロロベンゾジアゼピン−抗体結合体
WO2014057073A1 (en) 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
EP2906297B1 (en) 2012-10-12 2017-12-06 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
LT2906251T (lt) 2012-10-12 2017-12-11 Adc Therapeutics Sa Pirolobenzodiazepino-anti-cd22 antikūno konjugatai
EP2906250B1 (en) 2012-10-12 2018-05-30 ADC Therapeutics SA Pyrrolobenzodiazepine-anti-psma antibody conjugates
HUE045435T2 (hu) 2012-10-12 2019-12-30 Medimmune Ltd Pirrolobenzodiazepinek és konjugátumaik
JP6392764B2 (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
HRP20182129T1 (hr) 2012-10-12 2019-02-08 Adc Therapeutics Sa Konjugati protutijelo - pirolobenzodiazepin
AU2013366493B2 (en) 2012-12-21 2017-08-24 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US9567340B2 (en) 2012-12-21 2017-02-14 Medimmune Limited Unsymmetrical pyrrolobenzodiazepines-dimers for use in the treatment of proliferative and autoimmune diseases
CN105307685B (zh) 2013-03-13 2019-03-08 麦迪穆有限责任公司 吡咯并苯并二氮杂卓和其结合物
CA2904044C (en) 2013-03-13 2020-03-31 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
KR102306490B1 (ko) 2013-03-15 2021-09-28 리제너론 파아마슈티컬스, 인크. 생물학적 활성 분자, 그의 접합체 및 치료 용도
SG11201601230RA (en) 2013-08-26 2016-03-30 Regeneron Pharma Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
WO2015052532A1 (en) 2013-10-11 2015-04-16 Spirogen Sàrl Pyrrolobenzodiazepine-antibody conjugates
US9950078B2 (en) 2013-10-11 2018-04-24 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
US9956299B2 (en) 2013-10-11 2018-05-01 Medimmune Limited Pyrrolobenzodiazepine—antibody conjugates
KR102399005B1 (ko) 2014-03-11 2022-05-17 리제너론 파마슈티칼스 인코포레이티드 항-egfrviii 항체 및 그것의 용도
JP6531166B2 (ja) 2014-09-10 2019-06-12 メドイミューン・リミテッドMedImmune Limited ピロロベンゾジアゼピン及びそのコンジュゲート
GB201416112D0 (en) 2014-09-12 2014-10-29 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
EP3223854A1 (en) 2014-11-25 2017-10-04 ADC Therapeutics SA Pyrrolobenzodiazepine-antibody conjugates
CN107995912A (zh) 2015-03-27 2018-05-04 里珍纳龙药品有限公司 美登素类衍生物、其偶联物和使用方法
GB201506411D0 (en) 2015-04-15 2015-05-27 Bergenbio As Humanized anti-axl antibodies
GB201506402D0 (en) 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
KR20180025865A (ko) 2015-07-06 2018-03-09 리제너론 파마슈티칼스 인코포레이티드 다중특이적 항원 결합 분자 및 이의 용도
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
MX390630B (es) 2016-01-25 2025-03-21 Regeneron Pharma Derivados de maitansinoide, conjugados de los mismos y metodos de uso.
GB201601431D0 (en) 2016-01-26 2016-03-09 Medimmune Ltd Pyrrolobenzodiazepines
GB201602359D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
GB201602356D0 (en) 2016-02-10 2016-03-23 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
US11352446B2 (en) 2016-04-28 2022-06-07 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
JP2019524687A (ja) 2016-07-01 2019-09-05 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited 抗体薬物複合体およびこれを用いた治療方法
RS64691B1 (sr) 2016-09-23 2023-11-30 Regeneron Pharma Bispecifična anti-muc16-cd3 antitela i konjugati anti-muc16 sa lekom
AU2017331361B2 (en) 2016-09-23 2024-07-18 Regeneron Pharmaceuticals, Inc. 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
AU2017359043B2 (en) 2016-11-08 2022-06-16 Regeneron Pharmaceuticals, Inc. 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
KR20200032243A (ko) 2017-02-08 2020-03-25 에이디씨 테라퓨틱스 에스에이 피롤로벤조디아제핀-항체 컨주게이트
GB201702031D0 (en) 2017-02-08 2017-03-22 Medlmmune Ltd Pyrrolobenzodiazepine-antibody conjugates
SI3612537T1 (sl) 2017-04-18 2022-10-28 Medimmune Limited Konjugati pirolobenzodiazepina
EP3612234B1 (en) 2017-04-20 2024-03-13 ADC Therapeutics SA Combination therapy with an anti-axl antibody-drug conjugate
CN111065622A (zh) 2017-05-18 2020-04-24 里珍纳龙药品有限公司 双八氢菲羧酰胺类化合物及其蛋白质偶联物
KR20200007905A (ko) 2017-05-18 2020-01-22 리제너론 파마슈티칼스 인코포레이티드 사이클로덱스트린 단백질 약물 접합체
CN110809583A (zh) 2017-06-07 2020-02-18 瑞泽恩制药公司 用于内化酶的组合物和方法
KR102442736B1 (ko) 2017-06-14 2022-09-16 에이디씨 테라퓨틱스 에스에이 항-cd19 adc의 투여를 위한 투약량 체제
CN111065638B (zh) 2017-08-18 2021-04-09 麦迪穆有限责任公司 吡咯并苯并二氮杂䓬缀合物
IL301638B2 (en) 2017-09-29 2024-09-01 Daiichi Sankyo Co Ltd Antibody-pyrrolobenzodiazepine derivative conjugate
CA3080857A1 (en) 2017-11-07 2019-05-16 Regeneron Pharmaceuticals, Inc. Hydrophilic linkers for antibody drug conjugates
EA202091672A1 (ru) 2018-01-08 2021-02-01 Регенерон Фармасьютикалз, Инк. Стероиды и их антитело-конъюгаты
GB201803342D0 (en) 2018-03-01 2018-04-18 Medimmune Ltd Methods
SG11202009308WA (en) 2018-03-28 2020-10-29 Mitsubishi Tanabe Pharma Corp DRUG CONJUGATES OF cMET MONOCLONAL BINDING AGENTS, AND USES THEREOF
GB201806022D0 (en) 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
JP7328990B2 (ja) 2018-04-30 2023-08-17 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 Her2及び/またはaplp2に結合する抗体及び二重特異性抗原結合分子、ならびにそれらのコンジュゲート及び使用
WO2019217591A1 (en) 2018-05-09 2019-11-14 Regeneron Pharmaceuticals, Inc. Anti-msr1 antibodies and methods of use thereof
MX2020012350A (es) 2018-05-17 2021-01-29 Regeneron Pharma Anticuerpos anti-cd63, conjugados y usos de estos.
MY206542A (en) 2018-11-20 2024-12-20 Regeneron Pharma Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof for use as lxr agonists
CN113226470B (zh) 2018-12-21 2025-05-06 瑞泽恩制药公司 利福霉素类似物及其抗体-药物缀合物
EP3898651A2 (en) 2018-12-21 2021-10-27 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
KR102877468B1 (ko) 2019-01-08 2025-10-29 리제너론 파마슈티칼스 인코포레이티드 흔적이 없는 링커 및 이의 단백질-접합체
WO2020172475A1 (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
IL286326B2 (en) 2019-03-15 2025-10-01 Medimmune Ltd Azatidobenzodiazepine dimers and conjugates containing them for use in the treatment of cancer
KR20220063185A (ko) 2019-09-16 2022-05-17 리제너론 파마슈티칼스 인코포레이티드 면역-pet 영상화를 위한 방사성 표지된 met 결합 단백질
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
WO2021174113A1 (en) 2020-02-28 2021-09-02 Regeneron Pharmaceuticals, Inc. Bispecific antigen binding molecules that bind her2, and methods of use thereof
IL319200A (en) 2020-04-16 2025-04-01 Regeneron Pharma Antibody-drug conjugates prepared using Diels-Alder compression methods
JP2023533218A (ja) 2020-06-24 2023-08-02 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
US20220072141A1 (en) 2020-07-13 2022-03-10 Regeneron Pharmaceuticals, Inc. Protein-drug conjugates comprising camptothecin analogs and methods of use thereof
WO2022056494A1 (en) 2020-09-14 2022-03-17 Regeneron Pharmaceuticals, Inc. Antibody-drug conjugates comprising glp1 peptidomimetics and uses thereof
KR20230095070A (ko) 2020-10-22 2023-06-28 리제너론 파마슈티칼스 인코포레이티드 항-fgfr2 항체 및 이의 사용 방법
IL307947A (en) 2021-07-28 2023-12-01 Regeneron Pharma An antiviral compound of proteins
TW202330608A (zh) 2021-09-30 2023-08-01 大陸商江蘇恆瑞醫藥股份有限公司 吡咯并苯并二氮雜卓類衍生物及其偶聯物、其製備方法及其應用
US20230414775A1 (en) 2021-12-29 2023-12-28 Regeneron Pharmaceuticals, Inc. Tubulysins and protein-tubulysin conjugates
JP2025502147A (ja) 2022-01-12 2025-01-24 リジェネロン ファーマシューティカルズ,インク. タンパク質中のグルタミン残基にコンジュゲートしたカンプトテシンアナログおよびその使用
WO2023137443A1 (en) 2022-01-14 2023-07-20 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
AU2023298568A1 (en) 2022-06-30 2025-01-09 Toray Industries, Inc. Pharmaceutical composition for cancer treatment and/or prevention
WO2024020164A2 (en) 2022-07-21 2024-01-25 Firefly Bio, Inc. Glucocorticoid receptor agonists and conjugates thereof
KR20250128394A (ko) 2022-11-30 2025-08-27 리제너론 파마슈티칼스 인코포레이티드 Tlr7 작용제 및 이의 항체-약물-접합체
CN120752059A (zh) 2022-12-21 2025-10-03 瑞泽恩制药公司 用于adc缀合的拓扑异构酶i抑制剂的前药及其使用方法
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
WO2025014533A1 (en) 2023-07-10 2025-01-16 Regeneron Pharmaceuticals, Inc. Anti-human cacng1 antibody-drug conjugates and uses thereof
WO2025096921A1 (en) 2023-11-03 2025-05-08 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

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.
DK1193270T3 (da) * 1998-08-27 2003-09-15 Spirogen Ltd Pyrrolobenzodiazepiner
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
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
ATE516288T1 (de) 2003-10-22 2011-07-15 Us Gov Health & Human Serv Pyrrolobenzodiazepinderivate, zusammensetzungen, die diese enthalten, und damit in zusammenhang stehende verfahren
GB0416511D0 (en) 2003-10-22 2004-08-25 Spirogen Ltd Pyrrolobenzodiazepines
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
GB0404577D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
GB0404574D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Amino acids
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
JP5166861B2 (ja) * 2004-03-09 2013-03-21 スピロゲン リミティッド ピロロベンゾジアゼピン
GB0410725D0 (en) 2004-05-13 2004-06-16 Spirogen Ltd Pyrrolobenzodiazepine therapeutic agents
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
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

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AU2012322933B2 (en) 2017-02-02
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CN104011018A (zh) 2014-08-27
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