CN104684914B - 吡咯并苯并二氮杂卓 - Google Patents

吡咯并苯并二氮杂卓 Download PDF

Info

Publication number
CN104684914B
CN104684914B CN201380035167.5A CN201380035167A CN104684914B CN 104684914 B CN104684914 B CN 104684914B CN 201380035167 A CN201380035167 A CN 201380035167A CN 104684914 B CN104684914 B CN 104684914B
Authority
CN
China
Prior art keywords
alkyl
methyl
acid
aryl
examples
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.)
Expired - Fee Related
Application number
CN201380035167.5A
Other languages
English (en)
Chinese (zh)
Other versions
CN104684914A (zh
Inventor
菲利普·威尔逊·霍华德
戴维·瑟斯顿
洪达克·米拉祖尔·拉赫曼
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
ADC Therapeutics SA
UCL Biomedica PLC
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 ADC Therapeutics SA, UCL Biomedica PLC filed Critical ADC Therapeutics SA
Publication of CN104684914A publication Critical patent/CN104684914A/zh
Application granted granted Critical
Publication of CN104684914B publication Critical patent/CN104684914B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic 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
    • A61K31/55131,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/55171,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201380035167.5A 2012-04-30 2013-04-30 吡咯并苯并二氮杂卓 Expired - Fee Related CN104684914B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261640310P 2012-04-30 2012-04-30
US61/640,310 2012-04-30
PCT/GB2013/051098 WO2013164593A1 (en) 2012-04-30 2013-04-30 Pyrrolobenzodiazepines

Publications (2)

Publication Number Publication Date
CN104684914A CN104684914A (zh) 2015-06-03
CN104684914B true CN104684914B (zh) 2017-12-15

Family

ID=48325770

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201380035167.5A Expired - Fee Related CN104684914B (zh) 2012-04-30 2013-04-30 吡咯并苯并二氮杂卓

Country Status (14)

Country Link
US (1) US9376440B2 (https=)
EP (1) EP2855482B1 (https=)
JP (1) JP6157596B2 (https=)
KR (1) KR101960129B1 (https=)
CN (1) CN104684914B (https=)
AU (1) AU2013255613B2 (https=)
BR (1) BR112014027143B1 (https=)
CA (1) CA2871172C (https=)
ES (1) ES2623042T3 (https=)
IN (1) IN2014MN02092A (https=)
MX (1) MX369715B (https=)
NZ (1) NZ701290A (https=)
WO (1) WO2013164593A1 (https=)
ZA (1) ZA201407759B (https=)

Families Citing this family (55)

* 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
CA2795349C (en) 2010-04-15 2016-11-29 Seattle Genetics, Inc. Targeted pyrrolobenzodiazepine conjugates
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
SG11201400770SA (en) 2011-09-20 2014-04-28 Spirogen Sarl Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in 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
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
AU2012322932B2 (en) 2011-10-14 2016-11-10 Medimmune Limited Pyrrolobenzodiazepines
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
MX338711B (es) 2012-10-12 2016-04-28 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas.
HRP20190366T1 (hr) 2012-10-12 2019-04-19 Medimmune Limited Pirolobenzodiazepini i njihovi konjugati
EP2906249B1 (en) 2012-10-12 2018-06-27 MedImmune Limited Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
HRP20182129T1 (hr) 2012-10-12 2019-02-08 Adc Therapeutics Sa Konjugati protutijelo - pirolobenzodiazepin
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
CN204441379U (zh) * 2013-05-07 2015-07-01 株式会社Lg化学 二次电池用电极以及包含其的二次电池和线缆型二次电池
GB201317982D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
GB201317981D0 (en) 2013-10-11 2013-11-27 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
GB201407816D0 (en) 2014-05-02 2014-06-18 King S College London Pyrrolobenzodiazepine Compounds
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
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
GB201510010D0 (en) 2015-06-09 2015-07-22 King S College London PDD and BPD compounds
US20180339985A1 (en) 2015-08-21 2018-11-29 Femtogenix Limited Pdd compounds
GB201514928D0 (en) * 2015-08-21 2015-10-07 King S College London PDD compounds
GB201521709D0 (en) * 2015-12-09 2016-01-20 Kings College London And Sec Dep For Health The PBD Antibacterial agents
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
GB201607478D0 (en) 2016-04-29 2016-06-15 Medimmune Ltd Pyrrolobenzodiazepine Conjugates
TW201808936A (zh) 2016-05-18 2018-03-16 美商梅爾莎納醫療公司 吡咯并苯并二氮呯類及其共軛物
CN109641910A (zh) * 2016-06-24 2019-04-16 梅尔莎纳医疗公司 吡咯并苯二氮*及其缀合物
GB201617466D0 (en) 2016-10-14 2016-11-30 Medimmune Ltd Pyrrolobenzodiazepine conjugates
GB201702031D0 (en) 2017-02-08 2017-03-22 Medlmmune Ltd Pyrrolobenzodiazepine-antibody conjugates
RS61795B1 (sr) 2017-02-08 2021-06-30 Adc Therapeutics Sa Konjugati pirolobenzodiazepin antitela
CA3058360A1 (en) 2017-03-29 2018-10-04 Legochem Biosciences, Inc. Pyrrolobenzodiazepine dimer prodrug and ligand-linker conjugate compound of the same
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
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
WO2019104289A1 (en) 2017-11-27 2019-05-31 Mersana Therapeutics, Inc. Pyrrolobenzodiazepine antibody conjugates
CN111757757A (zh) 2017-12-21 2020-10-09 梅尔莎纳医疗公司 吡咯并苯并二氮呯抗体共轭物
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
WO2020141923A2 (ko) 2019-01-03 2020-07-09 주식회사 레고켐 바이오사이언스 안전성이 향상된 피롤로벤조디아제핀 이량체 화합물 및 이의 용도
KR20200084802A (ko) 2019-01-03 2020-07-13 주식회사 레고켐 바이오사이언스 안전성이 향상된 피롤로벤조디아제핀 이량체 화합물 및 이의 용도
GB201901197D0 (en) 2019-01-29 2019-03-20 Femtogenix Ltd G-A Crosslinking cytotoxic agents
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
GB2597532A (en) * 2020-07-28 2022-02-02 Femtogenix Ltd Cytotoxic compounds
EP4548932A1 (en) 2022-06-30 2025-05-07 Toray Industries, Inc. Pharmaceutical composition for treating and/or preventing cancer
GB202405758D0 (en) 2024-04-24 2024-06-05 King S College London Compounds

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1735616A (zh) * 2002-11-14 2006-02-15 斯皮罗根有限公司 吡咯并苯并二氮杂䓬
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
WO2009060208A1 (en) * 2007-11-09 2009-05-14 Spirogen Limited Pyrrolobenzodiazepines

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5569587A (en) 1978-11-17 1980-05-26 Meiji Seika Kaisha Ltd Novel antibiotic neothramycin 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
US5229490A (en) 1987-05-06 1993-07-20 The Rockefeller University Multiple antigen peptide system
DE69720773T2 (de) 1996-12-23 2004-01-29 Bristol Myers Squibb Pharma Co SAUERSTOFF ODER SCHWEFEL ENTHALTENDE 5-GLIEDRIGE HETEROAROMATISHE DERIVATIVE ALS FACTOR Xa HEMMER
US6187797B1 (en) 1996-12-23 2001-02-13 Dupont Pharmaceuticals Company Phenyl-isoxazoles as factor XA Inhibitors
WO1999046244A1 (en) 1998-03-12 1999-09-16 Novo Nordisk A/S Modulators of protein tyrosine phosphatases (ptpases)
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
GB9818732D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collection of compounds
GB9818730D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Collections of compounds
DE69925133T2 (de) 1998-08-27 2006-01-19 Spirogen Ltd., Ryde Pyrrolobenzodiazepine
US6909006B1 (en) 1999-08-27 2005-06-21 Spirogen Limited Cyclopropylindole derivatives
CA2392150A1 (en) 1999-12-20 2001-06-28 The University Of North Carolina At Chapel Hill Diamidine compounds as dna minor groove binders
US20040138269A1 (en) 2002-10-11 2004-07-15 Sugen, Inc. Substituted pyrroles as kinase inhibitors
GB0321295D0 (en) 2003-09-11 2003-10-15 Spirogen Ltd Synthesis of protected pyrrolobenzodiazepines
GB0404574D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Amino acids
GB0404577D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
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
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
DE102007029116A1 (de) * 2007-06-25 2009-01-02 Continental Automotive Gmbh Verfahren zum Betreiben eines Mikrocontrollers und einer Ausführungseinheit sowie ein Mikrocontroller und eine Ausführungseinheit
GB0813432D0 (en) 2008-07-22 2008-08-27 Spirogen Ltd Pyrrolobenzodiazepines
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1735616A (zh) * 2002-11-14 2006-02-15 斯皮罗根有限公司 吡咯并苯并二氮杂䓬
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
WO2009060208A1 (en) * 2007-11-09 2009-05-14 Spirogen Limited Pyrrolobenzodiazepines

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Antistaphylococcal activity of DNA-interactive pyrrolobenzodiazepine (PBD) dimers and PBD-biaryl conjugates;Khondaker M. Rahman,等;《J Antimicrob Chemother》;20120430;第67卷(第7期);第1683-1696页 *
GC-Targeted C8-Linked Pyrrolobenzodiazepine−Biaryl Conjugates with Femtomolar in Vitro Cytotoxicity and in Vivo Antitumor Activity in Mouse Models;Khondaker M. Rahman,等;《Journal of Medicinal Chemistry》;20130321;第56卷(第7期);第2911-2935页 *

Also Published As

Publication number Publication date
BR112014027143B1 (pt) 2020-06-09
ZA201407759B (en) 2015-11-25
EP2855482A1 (en) 2015-04-08
HK1208444A1 (en) 2016-03-04
US9376440B2 (en) 2016-06-28
BR112014027143A2 (pt) 2017-06-27
CA2871172C (en) 2020-08-25
CN104684914A (zh) 2015-06-03
KR101960129B1 (ko) 2019-03-19
ES2623042T3 (es) 2017-07-10
KR20150016245A (ko) 2015-02-11
EP2855482B1 (en) 2017-03-01
IN2014MN02092A (https=) 2015-09-04
JP2015515972A (ja) 2015-06-04
NZ701290A (en) 2016-08-26
AU2013255613A1 (en) 2014-11-13
US20150133435A1 (en) 2015-05-14
MX369715B (es) 2019-11-20
CA2871172A1 (en) 2013-11-07
JP6157596B2 (ja) 2017-07-05
MX2014013098A (es) 2015-04-14
AU2013255613B2 (en) 2017-06-22
WO2013164593A1 (en) 2013-11-07

Similar Documents

Publication Publication Date Title
CN104684914B (zh) 吡咯并苯并二氮杂卓
ES2338696T3 (es) Pirrolobenzodiazepinas.
ES2557283T3 (es) Dímeros de pirrolbenzodiazepinas asimétricas para el tratamiento de enfermedades proliferativas
CN104540827B (zh) 吡咯并苯并二氮杂卓
ES2623057T3 (es) Pirrolobenzodiazepinas usadas para tratar enfermedades proliferativas
EP1931671B1 (en) 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
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
HK1208444B (en) Pyrrolobenzodiazepines
HK1154575B (en) Unsymmetrical pyrrolobenzodiazepine-dimers for treatment of proliferative diseases

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C41 Transfer of patent application or patent right or utility model
CB02 Change of applicant information

Address after: Lausanne

Applicant after: SPIROGEN Ltd.

Applicant after: UCL BUSINESS PLC

Address before: Switzerland at Kiel Xie Texas

Applicant before: Spirogen Ltd.

Applicant before: UCL BUSINESS PLC

COR Change of bibliographic data
TA01 Transfer of patent application right

Effective date of registration: 20160127

Address after: cambridge

Applicant after: MEDIMMUNE LTD.

Applicant after: UCL BUSINESS PLC

Address before: Lausanne

Applicant before: Spirogen Ltd.

Applicant before: UCL BUSINESS PLC

GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20200113

Address after: England

Patentee after: MEDIMMUNE LTD.

Address before: England

Co-patentee before: UCL BUSINESS PLC

Patentee before: MEDIMMUNE LTD.

CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20171215

Termination date: 20210430