AU2016284340A1 - Macrocyclic benzodiazepine dimers, conjugates thereof, preparation and uses - Google Patents

Macrocyclic benzodiazepine dimers, conjugates thereof, preparation and uses Download PDF

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Publication number
AU2016284340A1
AU2016284340A1 AU2016284340A AU2016284340A AU2016284340A1 AU 2016284340 A1 AU2016284340 A1 AU 2016284340A1 AU 2016284340 A AU2016284340 A AU 2016284340A AU 2016284340 A AU2016284340 A AU 2016284340A AU 2016284340 A1 AU2016284340 A1 AU 2016284340A1
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alkyl
pct
independently
mmol
formula
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Abandoned
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AU2016284340A
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Inventor
Robert M. Borzilleri
Andrew F. DONNELL
Heidi L. PEREZ
Gretchen M. Schroeder
Erik M. Stang
Andrew J. Tebben
Donna D. Wei
Yong Zhang
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Bristol Myers Squibb Co
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Bristol Myers Squibb Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • 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
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    • 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
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    • 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
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    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
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    • C07K16/3023—Lung
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    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate

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  • Pharmacology & Pharmacy (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
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  • Biochemistry (AREA)
  • Biophysics (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
AU2016284340A 2015-06-23 2016-06-22 Macrocyclic benzodiazepine dimers, conjugates thereof, preparation and uses Abandoned AU2016284340A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562183350P 2015-06-23 2015-06-23
US62/183,350 2015-06-23
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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201806022D0 (en) * 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
IL311536A (en) * 2018-06-04 2024-05-01 Tufts College Binder-drug conjugates activated in the microenvironment and their related uses
WO2020112588A1 (en) 2018-11-30 2020-06-04 Bristol-Myers Squibb Company Antibody comprising a glutamine-containing light chain c-terminal extension, conjugates thereof, and methods and uses
US12478686B2 (en) 2018-12-12 2025-11-25 Bristol-Myers Squibb Company Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
MX2021010477A (es) 2019-03-15 2021-10-01 Medimmune Ltd Dimeros de azetidobenzodiazepina y conjugados que los comprenden para uso en el tratamiento de cancer.
US20240377413A1 (en) 2019-09-16 2024-11-14 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US612062A (en) 1898-10-11 Trolley-arm
DK1413582T3 (da) 1998-08-27 2006-07-17 Spirogen Ltd Dimere pyrrolobenzodiazepiner
SI2357006T1 (sl) 2002-07-31 2016-01-29 Seattle Genetics, Inc. Konjugati zdravil in njihova uporaba za zdravljenje raka, avtoimunske bolezni ali infekcijske bolezni
GB0226593D0 (en) 2002-11-14 2002-12-24 Consultants Ltd Compounds
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
ES2398975T3 (es) 2004-03-01 2013-03-25 Spirogen Sàrl Derivados de 11-hidroxi-5H-pirrolo[2,1-c][1,4]benzodiazepin-5-ona como intermedios clave para la preparación de pirrolobenzodiazepinas sustituidas en C2
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
SI1879901T1 (sl) 2005-04-21 2010-04-30 Spirogen Ltd Pirolobenzodiazepini
DK1813614T3 (da) 2006-01-25 2012-01-23 Sanofi Sa Cytotoksiske midler, der omfatter nye tomaymycinderivater
SI2019104T1 (sl) 2007-07-19 2013-12-31 Sanofi Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba
GB0813432D0 (en) 2008-07-22 2008-08-27 Spirogen Ltd Pyrrolobenzodiazepines
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
EP3100745B1 (en) 2009-02-05 2018-04-18 Immunogen, Inc. Novel benzodiazepine derivatives
FR2949469A1 (fr) 2009-08-25 2011-03-04 Sanofi Aventis Derives anticancereux, leur preparation et leur application en therapeutique
MX368648B (es) * 2010-04-15 2019-10-09 Seattle Genetics Inc Pirrolobenzodiazepinas usadas para tratar enfermedades proliferativas.
BR112012026213B1 (pt) 2010-04-15 2021-12-28 Medimmune Limited Compostos de pirrolobenzodiazepinas, conjugado das mesmas, composição farmacêutica compreendendo o conjugado e uso do mesmo para o tratamento de uma doença proliferativa
NZ602932A (en) 2010-04-15 2014-08-29 Seattle Genetics Inc Targeted pyrrolobenzodiazapine conjugates
FR2963007B1 (fr) 2010-07-26 2013-04-05 Sanofi Aventis Derives anticancereux, leur preparation et leur application therapeutique
EP2675479B1 (en) 2011-02-15 2016-01-13 Immunogen, Inc. Cytotoxic benzodiazepine derivatives
MX341524B (es) 2011-09-20 2016-08-24 Medimmune Ltd Pirrolobenzodiazepinas como compuestos pbd dimericos asimetricos para inclusion en conjugados dirigidos.
EP2751110B1 (en) 2011-10-14 2017-04-19 MedImmune Limited Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative and autoimmune diseases
SG11201401406YA (en) 2011-10-14 2014-05-29 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
CA2850373C (en) 2011-10-14 2019-07-16 Seattle Genetics, Inc. Pyrrolobenzodiazepines and targeted conjugates
KR101891859B1 (ko) 2011-10-14 2018-08-24 메디뮨 리미티드 피롤로벤조디아제핀
AU2012322613B2 (en) 2011-10-14 2016-04-21 Medimmune Limited Pyrrolobenzodiazepines and targeted conjugates
WO2013177481A1 (en) 2012-05-25 2013-11-28 Immunogen, Inc. Benzodiazepines and conjugates thereof
WO2014031566A1 (en) 2012-08-22 2014-02-27 Immunogen, Inc. Cytotoxic benzodiazepine derivatives
WO2014057074A1 (en) 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
ES2713164T3 (es) 2012-10-12 2019-05-20 Medimmune Ltd Pirrolobenzodiazepinas y conjugados de las mismas
WO2014080251A1 (en) 2012-11-24 2014-05-30 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
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
JP6307519B2 (ja) 2012-12-21 2018-04-04 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およびその結合体
EP2968596B1 (en) 2013-03-13 2019-03-06 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
JP6340019B2 (ja) * 2013-03-13 2018-06-06 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
AU2014230735B2 (en) 2013-03-13 2018-03-15 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
WO2014174111A1 (en) 2013-04-26 2014-10-30 Pierre Fabre Medicament Axl antibody-drug conjugate and its use for the treatment of cancer
US9456426B2 (en) 2013-12-06 2016-09-27 Qualcomm Incorporated Determining a gain factor for transmit power control in enhanced uplink

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