ES2260570T3 - Pirrolobenziodiazepinas dimericas. - Google Patents
Pirrolobenziodiazepinas dimericas.Info
- Publication number
- ES2260570T3 ES2260570T3 ES03028817T ES03028817T ES2260570T3 ES 2260570 T3 ES2260570 T3 ES 2260570T3 ES 03028817 T ES03028817 T ES 03028817T ES 03028817 T ES03028817 T ES 03028817T ES 2260570 T3 ES2260570 T3 ES 2260570T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- bis
- mmol
- tumor
- solution
- 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 - Lifetime
Links
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Classifications
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- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9818733.9A GB9818733D0 (en) | 1998-08-27 | 1998-08-27 | Compounds |
| HN9818733 | 1998-08-27 | ||
| GB9901929 | 1999-01-28 | ||
| GBGB9901929.1A GB9901929D0 (en) | 1999-01-28 | 1999-01-28 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2260570T3 true ES2260570T3 (es) | 2006-11-01 |
Family
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03028817T Expired - Lifetime ES2260570T3 (es) | 1998-08-27 | 1999-08-27 | Pirrolobenziodiazepinas dimericas. |
| ES99943066T Expired - Lifetime ES2244210T3 (es) | 1998-08-27 | 1999-08-27 | Pirrolobenzodiazepinas. |
| ES01129700T Expired - Lifetime ES2199200T3 (es) | 1998-08-27 | 1999-08-27 | Pirrolobenzodiacepinas. |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99943066T Expired - Lifetime ES2244210T3 (es) | 1998-08-27 | 1999-08-27 | Pirrolobenzodiazepinas. |
| ES01129700T Expired - Lifetime ES2199200T3 (es) | 1998-08-27 | 1999-08-27 | Pirrolobenzodiacepinas. |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US7049311B1 (enExample) |
| EP (3) | EP1109812B1 (enExample) |
| JP (1) | JP4824165B2 (enExample) |
| AT (3) | ATE240334T1 (enExample) |
| AU (1) | AU757510C (enExample) |
| CA (1) | CA2341471C (enExample) |
| DE (3) | DE69930328T2 (enExample) |
| DK (3) | DK1193270T3 (enExample) |
| ES (3) | ES2260570T3 (enExample) |
| NZ (1) | NZ510493A (enExample) |
| PT (3) | PT1193270E (enExample) |
| WO (1) | WO2000012508A2 (enExample) |
Families Citing this family (200)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9818730D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
| GB9818731D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
| GB9818732D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
| ES2260570T3 (es) | 1998-08-27 | 2006-11-01 | Spirogen Limited | Pirrolobenziodiazepinas dimericas. |
| GB0226593D0 (en) * | 2002-11-14 | 2002-12-24 | Consultants Ltd | Compounds |
| ATE421967T1 (de) * | 2003-03-31 | 2009-02-15 | Council Scient Ind Res | Nichtvernetzende pyrroloä2,1-cüä1, 4übenzodiazepine als potentielle antitumor- agentien und ihre herstellung |
| GB0321295D0 (en) * | 2003-09-11 | 2003-10-15 | Spirogen Ltd | Synthesis of protected pyrrolobenzodiazepines |
| AU2004284075A1 (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 |
| GB0416511D0 (en) * | 2003-10-22 | 2004-08-25 | Spirogen Ltd | Pyrrolobenzodiazepines |
| JPWO2005040172A1 (ja) * | 2003-10-29 | 2007-03-08 | 協和醗酵工業株式会社 | 三環性プロリン誘導体 |
| JP4718328B2 (ja) * | 2003-12-31 | 2011-07-06 | カウンシル オブ サイエンティフィク アンド インダストリアル リサーチ | Ｃ８連結したピロロ［２，１−ｃ］［１，４］ベンゾジアゼピン−アクリドン／アクリジン・ハイブリッド |
| AU2003300718A1 (en) * | 2003-12-31 | 2005-07-21 | Council Of Scientific And Industrial Research | Process for preparing pyrrolo(2, 1-c) (1, 4) benzodiazepine hybrids |
| GB0404577D0 (en) * | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0404578D0 (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 |
| GB0404574D0 (en) * | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Amino acids |
| EP1723152B1 (en) * | 2004-03-09 | 2015-02-11 | Spirogen Sàrl | Pyrrolobenzodiazepines |
| US6951853B1 (en) | 2004-03-30 | 2005-10-04 | Council Of Scientific And Industrial Research | Process for preparing pyrrolo[2, 1-c] [1,4] benzodiazepine hybrids |
| US7056913B2 (en) | 2004-03-30 | 2006-06-06 | Council Of Scientific And Industrial Research | C8—linked pyrrolo[2,1-c][1,4]benzodiazepine-acridone/acridine hybrids |
| FR2869231B1 (fr) * | 2004-04-27 | 2008-03-14 | Sod Conseils Rech Applic | Composition therapeutique contenant au moins un derive de la pyrrolobenzodiazepine et la fludarabine |
| GB0410725D0 (en) * | 2004-05-13 | 2004-06-16 | Spirogen Ltd | Pyrrolobenzodiazepine therapeutic agents |
| GB0508084D0 (en) * | 2005-04-21 | 2005-06-01 | Spirogen Ltd | Pyrrolobenzodiazepines |
| ES2338696T3 (es) | 2005-04-21 | 2010-05-11 | Spirogen Limited | Pirrolobenzodiazepinas. |
| DE602006006199D1 (de) * | 2005-10-05 | 2009-05-20 | Spirogen Ltd | 4-ä4-(5-oxo-2,3,5,11a-tetrahydro-5h-pyrrolo ä2, 1-cüä1,4übenzodiazepin-8-yloxy)-butyrylaminoü-1h-pyrrol-2-carbonsäurealkylesterderivate und verwandte verbindung zur behandlung einer proliferativen erkrankung |
| DK1813614T3 (da) | 2006-01-25 | 2012-01-23 | Sanofi Sa | Cytotoksiske midler, der omfatter nye tomaymycinderivater |
| DE102006013678A1 (de) * | 2006-03-24 | 2007-09-27 | Bayerische Motoren Werke Ag | Gleit- oder Schmiermittel und Verfahren zum Aufziehen eines Fahrzeugreifens auf eine Felge |
| ZA200900545B (en) | 2006-07-18 | 2010-03-31 | Sanofi Aventis | Antagonist antibody against EPHA2 for the treatment of cancer |
| GB0619325D0 (en) | 2006-09-30 | 2006-11-08 | Univ Strathclyde | New compounds |
| EP1914242A1 (en) | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Novel anti-CD38 antibodies for the treatment of cancer |
| PT2019104E (pt) | 2007-07-19 | 2013-12-03 | Sanofi Sa | Agentes citotóxicos compreendendo novos derivados de tomaimicina e sua utilização terapêutica |
| NZ588884A (en) | 2008-04-30 | 2013-05-31 | Immunogen Inc | Cross-linkers and their uses |
| GB0813432D0 (en) | 2008-07-22 | 2008-08-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819095D0 (en) * | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819097D0 (en) * | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| AU2015224492B2 (en) * | 2009-02-05 | 2017-04-20 | Immunogen, Inc. | Novel benzodiazepine derivatives |
| CA3014224C (en) | 2009-02-05 | 2022-05-24 | Immunogen, Inc. | Condensed benzodiazepine-indoline derivatives and processes to prepare said derivatives |
| JP5784592B2 (ja) | 2009-06-03 | 2015-09-24 | イミュノジェン・インコーポレーテッド | 抱合方法 |
| FR2949469A1 (fr) * | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| UY32914A (es) | 2009-10-02 | 2011-04-29 | Sanofi Aventis | Anticuerpos que se usan específicamente al receptor epha2 |
| CN103068405A (zh) | 2010-04-15 | 2013-04-24 | 西雅图基因公司 | 靶向吡咯并苯并二氮杂卓结合物 |
| MX368648B (es) | 2010-04-15 | 2019-10-09 | Seattle Genetics Inc | Pirrolobenzodiazepinas usadas para tratar enfermedades proliferativas. |
| GB201006340D0 (en) | 2010-04-15 | 2010-06-02 | Spirogen Ltd | Synthesis method and intermediates |
| PT2528625E (pt) | 2010-04-15 | 2013-10-17 | Spirogen Sarl | Pirrolobenzodiazepinas e conjugados das mesmas |
| FR2963007B1 (fr) | 2010-07-26 | 2013-04-05 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application therapeutique |
| SI2675480T1 (sl) | 2011-02-15 | 2019-05-31 | Immunogen, Inc. | Metode priprave konjugatov |
| FR2972006B1 (fr) | 2011-02-24 | 2016-03-25 | Centre Nat Rech Scient | Nouveaux fragments d'il-33 superactifs et leurs utilisations |
| US20130058947A1 (en) | 2011-09-02 | 2013-03-07 | Stem Centrx, Inc | Novel Modulators and Methods of Use |
| US9399641B2 (en) | 2011-09-20 | 2016-07-26 | Medimmune Limited | Pyrrolobenzodiazepines as unsymmetrical dimeric PBD compounds for inclusion in targeted conjugates |
| CA2850375C (en) | 2011-10-14 | 2019-07-02 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| AU2012322934B2 (en) | 2011-10-14 | 2016-09-08 | Medimmune Limited | Pyrrolobenzodiazepines |
| JP6104257B2 (ja) | 2011-10-14 | 2017-03-29 | 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コンジュゲート |
| CA2850373C (en) | 2011-10-14 | 2019-07-16 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| JP6166728B2 (ja) * | 2011-10-14 | 2017-07-19 | 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の製造に有用な合成方法及び中間体 |
| CA2850264C (en) | 2011-10-14 | 2019-11-05 | Medimmune Limited | Pyrrolobenzodiazepines |
| CN104520324A (zh) | 2012-02-24 | 2015-04-15 | 施特姆森特Rx股份有限公司 | Dll3调节剂及其使用方法 |
| RU2691698C2 (ru) | 2012-02-24 | 2019-06-17 | ЭББВИ СТЕМСЕНТРКС ЭлЭлСи | Антитела против sez6 и способы их применения |
| AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
| IN2014MN02092A (enExample) | 2012-04-30 | 2015-09-04 | Spirogen Sarl | |
| IN2014MN02175A (enExample) | 2012-04-30 | 2015-08-28 | Ucl Business Plc | |
| KR20150006000A (ko) | 2012-05-01 | 2015-01-15 | 제넨테크, 인크. | 항-pmel17 항체 및 면역접합체 |
| KR20150027829A (ko) | 2012-07-09 | 2015-03-12 | 제넨테크, 인크. | 항-cd22 항체를 포함하는 면역접합체 |
| BR112015000437A2 (pt) | 2012-07-09 | 2017-06-27 | Genentech Inc | imunoconjugados, formulação farmacêutica, métodos de tratamento e de inbir a proliferação de uma célula |
| BR112015002193A2 (pt) | 2012-08-02 | 2017-07-04 | Genentech Inc | anticorpos anti-etbr e imunoconjugados |
| HK1211208A1 (zh) | 2012-08-22 | 2016-05-20 | Immunogen, Inc. | 細胞毒性苯並二氮呯衍生物 |
| PT2906248T (pt) | 2012-10-12 | 2019-03-04 | Medimmune Ltd | Pirrolobenzodiazepinas e conjugados das mesmas |
| EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| BR112015008238A2 (pt) | 2012-10-12 | 2017-11-28 | Adc Therapeutics Sarl | conjugados de pirrolbenzodiazepina-anticorpo anti-cd22 |
| KR101995620B1 (ko) | 2012-10-12 | 2019-07-03 | 에이디씨 테라퓨틱스 에스에이 | 피롤로벤조디아제핀-항체 컨주게이트 |
| PT2906253T (pt) | 2012-10-12 | 2018-11-05 | Medimmune Ltd | Conjugados de anticorpo anti-psma de pirrolobenzodiazepina |
| EP2906249B1 (en) | 2012-10-12 | 2018-06-27 | MedImmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| WO2014057114A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-anti-psma antibody conjugates |
| DK2906298T3 (en) | 2012-10-12 | 2018-12-17 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
| DK2839860T3 (da) | 2012-10-12 | 2019-06-17 | Medimmune Ltd | Pyrrolobenzodiazepiner og konjugater deraf |
| US10131682B2 (en) | 2012-11-24 | 2018-11-20 | Hangzhou Dac Biotech Co., Ltd. | Hydrophilic linkers and their uses for conjugation of drugs to a cell binding molecules |
| US9567340B2 (en) | 2012-12-21 | 2017-02-14 | Medimmune Limited | Unsymmetrical pyrrolobenzodiazepines-dimers for use in the treatment of proliferative and autoimmune diseases |
| AU2013366493B2 (en) | 2012-12-21 | 2017-08-24 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| ES2731681T3 (es) | 2013-02-22 | 2019-11-18 | Abbvie Stemcentrx Llc | Conjugados de anticuerpo anti-DLL3 y PBD y usos de los mismos |
| ES2687439T3 (es) | 2013-03-13 | 2018-10-25 | Medimmune Limited | Pirrolobenzodiazepinas y conjugados de las mismas |
| KR102066318B1 (ko) | 2013-03-13 | 2020-01-14 | 메디뮨 리미티드 | 피롤로벤조디아제핀 및 그의 컨쥬게이트 |
| MX363787B (es) | 2013-03-13 | 2019-04-03 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de los mismos. |
| US9562099B2 (en) | 2013-03-14 | 2017-02-07 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
| MX2015010777A (es) | 2013-03-14 | 2016-04-25 | Genentech Inc | Anticuerpos e inmunoconjugados anti-b7-h4. |
| BR112016002829A2 (pt) | 2013-08-12 | 2017-09-19 | Genentech Inc | Composto e processo para preparar o composto de conjugado anticorpo-¿droga, composição farmacêutica, método de tratamento do câncer, kit para o tratamento do câncer, intermediário ligante¿-droga, porção e composto de porção droga de dímero cbi |
| JP2016531915A (ja) | 2013-08-28 | 2016-10-13 | ステムセントリックス， インコーポレイテッド | 部位特異的抗体コンジュゲーション方法および組成物 |
| CA2922529A1 (en) | 2013-08-28 | 2015-03-05 | Stemcentrx, Inc. | Novel sez6 modulators and methods of use |
| WO2015038984A2 (en) | 2013-09-12 | 2015-03-19 | Halozyme, Inc. | Modified anti-epidermal growth factor receptor antibodies and methods of use thereof |
| BR112016004450A2 (pt) | 2013-09-17 | 2017-10-17 | Genentech Inc | métodos para tratar uma doença, para aumentar a eficácia de um tratamento, para adiar e/ou prevenir desenvolvimento da reincidência e/ou resistência de uma doença, para aumentar a sensibilidade a um inibidor, para estender o período de sensibilidade a um inibidor e para estender a duração de resposta a um inibidor |
| 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 |
| US10010624B2 (en) | 2013-10-11 | 2018-07-03 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| 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 |
| AU2014346792A1 (en) | 2013-11-06 | 2016-06-02 | Abbvie Stemcentrx Llc | Novel anti-claudin antibodies and methods of use |
| CN115504924A (zh) | 2013-11-27 | 2022-12-23 | 雷德伍德生物科技股份有限公司 | 肼基-吡咯并化合物及用于生成缀合物的方法 |
| KR20160097336A (ko) | 2013-12-12 | 2016-08-17 | 스템센트알엑스 인코포레이티드 | 신규 항-ｄｐｅｐ3 항체 및 이의 사용 방법 |
| AR098743A1 (es) | 2013-12-13 | 2016-06-08 | Genentech Inc | Anticuerpos e inmunoconjugados anti-cd33 |
| JP6980384B2 (ja) | 2013-12-16 | 2021-12-15 | ジェネンテック， インコーポレイテッド | １−（クロロメチル）−２，３−ジヒドロ−１ｈ−ベンゾ［ｅ］インドール二量体抗体−薬物コンジュゲート化合物、並びに使用及び処置の方法 |
| EP3107576A4 (en) | 2014-02-21 | 2017-09-06 | Abbvie Stemcentrx LLC | Anti-dll3 antibodies and drug conjugates for use in melanoma |
| JP6417421B2 (ja) | 2014-02-28 | 2018-11-07 | ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． | 荷電連結体及び共役体のためのその使用 |
| GB201407816D0 (en) | 2014-05-02 | 2014-06-18 | King S College London | Pyrrolobenzodiazepine Compounds |
| JP2017522861A (ja) | 2014-05-22 | 2017-08-17 | ジェネンテック， インコーポレイテッド | 抗ｇｐｃ３抗体及びイムノコンジュゲート |
| DK3186284T3 (da) | 2014-08-28 | 2022-05-09 | Bioatla Inc | Betinget aktive kimæriske antigenreceptorer til modificerede t-celler |
| EP3189057A1 (en) | 2014-09-03 | 2017-07-12 | ImmunoGen, Inc. | Cytotoxic benzodiazepine derivatives |
| CR20170111A (es) | 2014-09-03 | 2017-05-23 | Immunogen Inc | Derivados de benzodiazepina citotóxicos |
| TW201617368A (zh) | 2014-09-05 | 2016-05-16 | 史坦森特瑞斯公司 | 新穎抗ｍｆｉ２抗體及使用方法 |
| 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 |
| TW201625689A (zh) | 2014-09-12 | 2016-07-16 | 建南德克公司 | 抗－ｂ７－ｈ４抗體及免疫結合物 |
| JP2017531620A (ja) | 2014-09-12 | 2017-10-26 | ジェネンテック， インコーポレイテッド | システイン操作抗体及びコンジュゲート |
| SI3191135T1 (sl) | 2014-09-12 | 2021-01-29 | Genentech, Inc. | Anti-HER2 protitelesa in imunokonjugati |
| MA40579A (fr) | 2014-09-12 | 2016-03-17 | Genentech Inc | Anticorps anti-cll-1 et immunoconjugués |
| CA2957148A1 (en) | 2014-09-17 | 2016-03-24 | Genentech, Inc. | Immunoconjugates comprising anti-her2 antibodies and pyrrolobenzodiazepines |
| 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 |
| KR102693806B1 (ko) | 2014-12-11 | 2024-08-09 | 피에르 파브르 메디카먼트 | 항-c10orf54 항체들 및 그들의 용도들 |
| TW201632531A (zh) | 2015-01-14 | 2016-09-16 | 必治妥美雅史谷比公司 | 苯二氮呯二聚物，其結合物及製造與使用方法 |
| CN107231804B (zh) | 2015-01-14 | 2019-11-26 | 百时美施贵宝公司 | 亚杂芳基桥连苯并二氮杂*二聚体、其缀合物及制备和使用方法 |
| 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 |
| GB201510010D0 (en) | 2015-06-09 | 2015-07-22 | King S College London | PDD and BPD compounds |
| EP3307749A4 (en) | 2015-06-15 | 2019-06-19 | Hangzhou Dac Biotech Co., Ltd | HYDROPHILIC LINKER FOR CONJUGATION |
| AU2016284340A1 (en) | 2015-06-23 | 2018-02-08 | Bristol-Myers Squibb Company | Macrocyclic benzodiazepine dimers, conjugates thereof, preparation and uses |
| CA2991973C (en) | 2015-07-12 | 2021-12-07 | Suzhou M-Conj Biotech Co., Ltd. | Bridge linkers for conjugation of a cell-binding molecule |
| US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
| EP3778602B1 (en) | 2015-07-21 | 2023-07-12 | ImmunoGen, Inc. | Methods of preparing cytotoxic benzodiazepine derivatives |
| 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 |
| EP4477269A3 (en) | 2015-09-20 | 2025-03-19 | The United States of America, as Represented By the Secretary, Department of Health and Human Services | Monoclonal antibodies specific for fibroblast growth factor receptor 4 (fgfr4) and methods of their use |
| CR20180243A (es) | 2015-10-02 | 2018-07-31 | Genentech Inc | Conjugados de anticuerpo-fármaco de pirrolobenzodiazepina y métodos de uso |
| MA43354A (fr) | 2015-10-16 | 2018-08-22 | Genentech Inc | Conjugués médicamenteux à pont disulfure encombré |
| WO2017083306A1 (en) | 2015-11-09 | 2017-05-18 | R.P. Scherer Technologies, Llc | Anti-cd22 antibody-maytansine conjugates and methods of use thereof |
| 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 |
| WO2017161206A1 (en) | 2016-03-16 | 2017-09-21 | Halozyme, Inc. | Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use |
| KR102775461B1 (ko) | 2016-04-01 | 2025-02-28 | 어비디티 바이오사이언시스 인크. | 핵산-폴리펩타이드 조성물 및 이의 용도 |
| EP4656204A3 (en) | 2016-04-15 | 2026-06-03 | BioAtla, Inc. | Anti-axl antibodies, antibody fragments and their immunoconjugates and uses thereof |
| EP3454864A4 (en) | 2016-04-21 | 2021-01-13 | Abbvie Stemcentrx LLC | Novel anti-bmpr1b antibodies and methods of use |
| GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| WO2017196847A1 (en) | 2016-05-10 | 2017-11-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Variable new antigen receptor (vnar) antibodies and antibody conjugates targeting tumor and viral antigens |
| WO2017194568A1 (en) | 2016-05-11 | 2017-11-16 | Sanofi | Treatment regimen using anti-muc1 maytansinoid immunoconjugate antibody for the treatment of tumors |
| EP4122958A1 (en) | 2016-05-13 | 2023-01-25 | BioAtla, Inc. | Anti-ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof |
| CN109313200B (zh) | 2016-05-27 | 2022-10-04 | 豪夫迈·罗氏有限公司 | 用于表征位点特异性抗体-药物缀合物的生物分析性方法 |
| WO2017214182A1 (en) | 2016-06-07 | 2017-12-14 | The United States Of America. As Represented By The Secretary, Department Of Health & Human Services | Fully human antibody targeting pdi for cancer immunotherapy |
| AU2017305170A1 (en) | 2016-08-02 | 2019-02-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal antibodies targeting glypican-2 (GPC2) and use thereof |
| EP3494139B1 (en) | 2016-08-05 | 2022-01-12 | F. Hoffmann-La Roche AG | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
| WO2018031662A1 (en) | 2016-08-11 | 2018-02-15 | Genentech, Inc. | Pyrrolobenzodiazepine prodrugs and antibody conjugates thereof |
| CN109862919A (zh) | 2016-10-11 | 2019-06-07 | 免疫医疗有限公司 | 抗体-药物缀合物联合免疫介导的治疗剂 |
| GB201617466D0 (en) | 2016-10-14 | 2016-11-30 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
| KR20220147719A (ko) | 2016-11-14 | 2022-11-03 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| CA3036983A1 (en) | 2016-11-21 | 2018-05-24 | Cureab Gmbh | Anti-gp73 antibodies and immunoconjugates |
| FR3059550B1 (fr) | 2016-12-01 | 2020-01-03 | Universite De Rouen Normandie | Traitement des troubles causes par l'alcoolisation foetale (tcaf) |
| EP3559038B1 (en) | 2016-12-21 | 2022-12-14 | The United States of America as represented by The Secretary Department of Health and Human Services | Human monoclonal antibodies specific for flt3 and uses thereof |
| 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 |
| SMT202200490T1 (it) * | 2017-04-18 | 2023-01-13 | Medimmune Ltd | Coniugati di pirrolobenzodiazepina |
| WO2018195243A1 (en) | 2017-04-20 | 2018-10-25 | Immunogen, Inc. | Cytotoxic benzodiazepine derivatives and conjugates thereof |
| WO2018193102A1 (en) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
| US11389480B2 (en) | 2017-05-19 | 2022-07-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibody targeting TNFR2 for cancer immunotherapy |
| KR102442736B1 (ko) | 2017-06-14 | 2022-09-16 | 에이디씨 테라퓨틱스 에스에이 | 항-cd19 adc의 투여를 위한 투약량 체제 |
| WO2019005208A1 (en) | 2017-06-30 | 2019-01-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | ANTIBODIES TO HUMAN MESOTHELIN AND USES IN ANTICANCER THERAPY |
| WO2019006280A1 (en) | 2017-06-30 | 2019-01-03 | Lentigen Technology, Inc. | HUMAN MONOCLONAL ANTIBODIES SPECIFIC TO CD33 AND METHODS OF USE |
| CN111201030B (zh) | 2017-07-25 | 2024-11-01 | 真和制药有限公司 | 通过阻断tim-3和其配体的相互作用治疗癌症 |
| SI3668874T1 (sl) | 2017-08-18 | 2022-04-29 | Medimmune Limited | Pirolobenzodiazepinski konjugati |
| CA3177215C (en) | 2017-09-29 | 2026-06-09 | Daiichi Sankyo Company, Limited | Antibody-pyrrolobenzodiazepine derivative conjugate |
| ES2920123T3 (es) | 2017-11-14 | 2022-08-01 | Medimmune Ltd | Conjugados de pirrolobenzodiazepina |
| EP3724225A1 (en) | 2017-12-15 | 2020-10-21 | Juno Therapeutics, Inc. | Anti-cct5 binding molecules and methods of use thereof |
| WO2019133652A1 (en) | 2017-12-28 | 2019-07-04 | Immunogen, Inc. | Benzodiazepine derivatives |
| GB201803342D0 (en) * | 2018-03-01 | 2018-04-18 | Medimmune Ltd | Methods |
| GB201806022D0 (en) | 2018-04-12 | 2018-05-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| US20210283141A1 (en) | 2018-05-25 | 2021-09-16 | Medimmune Limited | Pyrrolobenzodiazepine conjugates |
| FR3081707A1 (fr) | 2018-05-30 | 2019-12-06 | Universite De Rouen Normandie | Traitement des troubles neurologiques causes par l'alcoolisation foetale |
| JP7459043B2 (ja) | 2018-07-12 | 2024-04-01 | ザ ユナイテッド ステイツ オブ アメリカ， アズ リプレゼンテッド バイ ザ セクレタリー， デパートメント オブ ヘルス アンド ヒューマン サービシーズ | 親和性成熟ｃｄ２２特異的モノクローナル抗体およびその使用 |
| CA3106544A1 (en) | 2018-08-08 | 2020-02-13 | Mitchell Ho | High affinity monoclonal antibodies targeting glypican-2 and uses thereof |
| KR20210081350A (ko) | 2018-10-19 | 2021-07-01 | 메드임뮨 리미티드 | 피롤로벤조디아제핀 컨쥬게이트 |
| WO2020079239A1 (en) | 2018-10-19 | 2020-04-23 | Medimmune Limited | Pyrrolobenzodiazepine conjugates |
| CN113302207B (zh) | 2018-11-16 | 2025-05-13 | 维尔托索宾科公司 | Cd38和icam1抗体及其用途 |
| IL312067B2 (en) | 2018-12-21 | 2025-08-01 | Avidity Biosciences Inc | Anti-transferrin receptor antibodies and uses thereof |
| AU2020206308B2 (en) | 2019-01-08 | 2026-02-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cross-species single domain antibodies targeting mesothelin for treating solid tumors |
| WO2020154150A1 (en) | 2019-01-22 | 2020-07-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | High affinity monoclonal antibodies targeting glypican-1 and methods of use |
| KR20210124308A (ko) | 2019-01-30 | 2021-10-14 | 트루바인딩 아이엔씨. | 항-gal3 항체 및 이의 용도 |
| 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 |
| US20230094471A1 (en) | 2019-03-29 | 2023-03-30 | Immunogen, Inc. | Cytotoxic bis-benzodiazepine derivatives and conjugates thereof with cell-binding agents for inhibiting abnormal cell growth or for treating proliferative diseases |
| CA3156761A1 (en) | 2019-10-22 | 2021-04-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | High affinity nanobodies targeting b7h3 (cd276) for treating multiple solid tumors |
| CN115279789A (zh) | 2019-12-06 | 2022-11-01 | 真和制药有限公司 | 破坏gal3和胰岛素受体或整联蛋白的相互作用的抗体及其使用方法 |
| EP4041769A1 (en) | 2019-12-12 | 2022-08-17 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Antibody-drug conjugates specific for cd276 and uses thereof |
| TW202144572A (zh) | 2020-03-19 | 2021-12-01 | 美商亞維代堤生物科學公司 | 治療臉肩胛肱骨肌肉失養症之組合物及方法 |
| KR102927945B1 (ko) | 2020-03-27 | 2026-02-23 | 어비디티 바이오사이언시스 인크. | 근이영양증의 치료용 조성물 및 방법 |
| MX2022014786A (es) | 2020-05-26 | 2023-01-16 | Truebinding Inc | Metodos para tratar enfermedades inflamatorias mediante el bloqueo de galectina-3. |
| WO2022093745A1 (en) | 2020-10-26 | 2022-05-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting sars coronavirus spike protein and uses thereof |
| WO2022232612A1 (en) | 2021-04-29 | 2022-11-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Lassa virus-specific nanobodies and methods of their use |
| CA3216228A1 (en) | 2021-06-09 | 2022-12-15 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cross species single domain antibodies targeting pd-l1 for treating solid tumors |
| JP2024526764A (ja) | 2021-07-13 | 2024-07-19 | トゥルーバインディング，インコーポレイテッド | タンパク質凝集を防止する方法 |
| EP4401792A4 (en) | 2021-09-16 | 2025-12-03 | Avidity Biosciences Inc | COMPOSITIONS AND METHODS OF TREATMENT OF FACIO-SCAPULO-HUMERAL MUSCULAR DYSTROPHY |
| CN117980327A (zh) | 2021-11-03 | 2024-05-03 | 杭州多禧生物科技有限公司 | 抗体的特异性偶联 |
| US20230279120A1 (en) | 2021-11-09 | 2023-09-07 | Truebinding, Inc. | Methods of treating or inhibiting cardiovascular diseases |
| PE20242350A1 (es) | 2022-05-03 | 2024-12-16 | Genentech Inc | Anticuerpos anti-ly6e, inmunoconjugados y usos de estos |
| WO2025019228A1 (en) | 2023-07-20 | 2025-01-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Fully human monoclonal antibodies and chimeric antigen receptors against cd276 for the treatment of solid tumors |
| AU2025218272A1 (en) | 2024-02-07 | 2026-06-25 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal antibodies that bind the juxta-membrane region of mesothelin and uses thereof |
| WO2026165109A1 (en) | 2025-01-28 | 2026-08-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Tem8 monoclonal antibodies and their use |
| CN120965770A (zh) * | 2025-06-04 | 2025-11-18 | 广西师范大学 | 香草酸衍生芳烃钌配合物及其制备方法与应用 |
Family Cites Families (38)
| 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 |
| 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 |
| US4427588A (en) * | 1982-11-08 | 1984-01-24 | Bristol-Myers Company | Process for conversion of oxotomaymycin to tomaymycin |
| 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 |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| AU617304B2 (en) | 1986-12-19 | 1991-11-28 | Pharmacia & Upjohn Company | Novel cc-1065 analogs |
| GB8705477D0 (en) | 1987-03-09 | 1987-04-15 | Carlton Med Prod | Drug delivery systems |
| GB8809616D0 (en) | 1988-04-22 | 1988-05-25 | Cancer Res Campaign Tech | Further improvements relating to drug delivery systems |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| AU648313B2 (en) | 1990-04-25 | 1994-04-21 | Pharmacia & Upjohn Company | Novel CC-1065 analogs |
| 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. |
| JP4115514B2 (ja) | 1991-10-23 | 2008-07-09 | キャンサー・リサーチ・キヤンペーン・テクノロジー・リミテツド | Ｃｂ １９５４およびその類似体を細胞障害性の形態に還元するための細菌のニトロリダクターゼ |
| GB9205051D0 (en) | 1992-03-09 | 1992-04-22 | Cancer Res Campaign Tech | Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them |
| US5288514A (en) | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
| US5502068A (en) | 1995-01-31 | 1996-03-26 | Synphar Laboratories, Inc. | Cyclopropylpyrroloindole-oligopeptide anticancer agents |
| EP0850238A4 (en) | 1995-06-29 | 1998-10-07 | Pharmacopeia Inc | COMBINATORY LIBRARY OF 1,4-BENZODIAZEPINE-2,5-DIONES |
| GB9516943D0 (en) | 1995-08-18 | 1995-10-18 | Cancer Soc Auckland Div Nz Inc | Novel cyclopropylindoles and their secoprecursors,and their use as prodrugs |
| ATE310725T1 (de) | 1996-09-12 | 2005-12-15 | Auckland Uniservices Ltd | Kondensierte n-acylindole als antitumormittel |
| JPH1087666A (ja) | 1996-09-18 | 1998-04-07 | Kyorin Pharmaceut Co Ltd | デュオカルマイシンｓａ及びその誘導体の製造中間体と製造方法 |
| IL136489A0 (en) | 1997-12-08 | 2001-06-14 | Scripps Research Inst | Synthesis of cc-1065/duocarmycin analogs |
| WO1999046244A1 (en) | 1998-03-12 | 1999-09-16 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (ptpases) |
| GB9818732D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
| ES2260570T3 (es) | 1998-08-27 | 2006-11-01 | Spirogen Limited | Pirrolobenziodiazepinas dimericas. |
| GB9818730D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
| GB9818731D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
| GB9909612D0 (en) | 1999-04-26 | 1999-06-23 | Cancer Res Campaign Tech | N-protected amines and their use as prodrugs |
| US6660856B2 (en) | 2002-03-08 | 2003-12-09 | Kaohsiung Medical University | Synthesis of pyrrolo[2,1-c][1,4]benzodiazepine analogues |
| 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 |
| AU2004284075A1 (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 |
| 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 |
-
1999
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- 1999-08-27 AT AT01129700T patent/ATE240334T1/de active
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- 1999-08-27 NZ NZ510493A patent/NZ510493A/en not_active IP Right Cessation
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- 1999-08-27 US US09/763,767 patent/US7049311B1/en not_active Expired - Lifetime
-
2001
- 2001-12-12 US US10/021,213 patent/US7067511B2/en not_active Expired - Lifetime
-
2006
- 2006-03-02 US US11/367,241 patent/US7265105B2/en not_active Expired - Lifetime
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