EA028457B1 - Пирролобензодиазепины - Google Patents
Пирролобензодиазепины Download PDFInfo
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- EA028457B1 EA028457B1 EA201490535A EA201490535A EA028457B1 EA 028457 B1 EA028457 B1 EA 028457B1 EA 201490535 A EA201490535 A EA 201490535A EA 201490535 A EA201490535 A EA 201490535A EA 028457 B1 EA028457 B1 EA 028457B1
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- EA
- Eurasian Patent Office
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- YUOCYTRGANSSRY-UHFFFAOYSA-N pyrrolo[2,3-i][1,2]benzodiazepine Chemical class C1=CN=NC2=C3C=CN=C3C=CC2=C1 YUOCYTRGANSSRY-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- -1 methylthiophenyl Chemical group 0.000 claims abstract description 154
- 125000001424 substituent group Chemical group 0.000 claims abstract description 67
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 38
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 239000003446 ligand Substances 0.000 claims description 92
- 125000005647 linker group Chemical group 0.000 claims description 77
- 239000003814 drug Substances 0.000 claims description 73
- 229940079593 drug Drugs 0.000 claims description 72
- 125000000623 heterocyclic group Chemical group 0.000 claims description 49
- 108010016626 Dipeptides Proteins 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 229910052700 potassium Inorganic materials 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000002947 alkylene group Chemical group 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 239000012634 fragment Substances 0.000 claims description 20
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 17
- 230000027455 binding Effects 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
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- 125000004076 pyridyl group Chemical group 0.000 claims description 10
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
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- ALBODLTZUXKBGZ-JUUVMNCLSA-N (2s)-2-amino-3-phenylpropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC1=CC=CC=C1 ALBODLTZUXKBGZ-JUUVMNCLSA-N 0.000 claims description 2
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 2
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims description 2
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- IEPBPSSCIZTJIF-UHFFFAOYSA-N bis(2,2,2-trichloroethyl) carbonate Chemical compound ClC(Cl)(Cl)COC(=O)OCC(Cl)(Cl)Cl IEPBPSSCIZTJIF-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
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- 150000001413 amino acids Chemical class 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
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Classifications
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Transplantation (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547198P | 2011-10-14 | 2011-10-14 | |
| PCT/EP2012/070233 WO2013053873A1 (en) | 2011-10-14 | 2012-10-12 | Pyrrolobenzodiazepines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201490535A1 EA201490535A1 (ru) | 2014-09-30 |
| EA028457B1 true EA028457B1 (ru) | 2017-11-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201490535A EA028457B1 (ru) | 2011-10-14 | 2012-10-12 | Пирролобензодиазепины |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9399073B2 (OSRAM) |
| EP (1) | EP2751111B1 (OSRAM) |
| JP (1) | JP6170497B2 (OSRAM) |
| KR (1) | KR101891859B1 (OSRAM) |
| CN (1) | CN103998450B (OSRAM) |
| AU (1) | AU2012322934B2 (OSRAM) |
| BR (1) | BR112014008888A2 (OSRAM) |
| CA (1) | CA2850103C (OSRAM) |
| EA (1) | EA028457B1 (OSRAM) |
| MX (1) | MX341523B (OSRAM) |
| SG (1) | SG11201401021TA (OSRAM) |
| WO (1) | WO2013053873A1 (OSRAM) |
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| 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 |
| KR101671360B1 (ko) | 2010-04-15 | 2016-11-01 | 시애틀 지네틱스, 인크. | 표적화된 피롤로벤조디아제핀 접합체 |
| MX341524B (es) | 2011-09-20 | 2016-08-24 | Medimmune Ltd | Pirrolobenzodiazepinas como compuestos pbd dimericos asimetricos para inclusion en conjugados dirigidos. |
| WO2013055990A1 (en) | 2011-10-14 | 2013-04-18 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| EA026643B1 (ru) | 2011-10-14 | 2017-04-28 | Сиэтл Дженетикс, Инк. | Пирролбензодиазепины и конъюгаты направленного действия |
| EA027386B1 (ru) | 2011-10-14 | 2017-07-31 | Медимьюн Лимитед | Пирролобензодиазепины |
| US9399073B2 (en) | 2011-10-14 | 2016-07-26 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines |
| RS57104B1 (sr) | 2012-10-12 | 2018-06-29 | Adc Therapeutics Sa | Konjugati pirolobenzodiazepin-antitela |
| WO2014057120A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| NZ707534A (en) | 2012-10-12 | 2018-08-31 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
| ES2713164T3 (es) | 2012-10-12 | 2019-05-20 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas |
| EP2906253B9 (en) | 2012-10-12 | 2019-02-27 | ADC Therapeutics SA | Pyrrolobenzodiazepine - anti-psma antibody conjugates |
| 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 |
| AU2013328580B2 (en) | 2012-10-12 | 2016-01-21 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| US9745303B2 (en) | 2012-10-12 | 2017-08-29 | 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 |
| EA032986B1 (ru) | 2012-12-21 | 2019-08-30 | Медимьюн Лимитед | Пирролобензодиазепины |
| CA2894961C (en) | 2012-12-21 | 2020-09-15 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| US9649390B2 (en) | 2013-03-13 | 2017-05-16 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| US9610361B2 (en) | 2013-03-13 | 2017-04-04 | Seattle Genetics, Inc. | Cyclodextrin and antibody-drug conjugate formulations |
| EP2968494B1 (en) | 2013-03-13 | 2018-11-14 | Seattle Genetics, Inc. | Activated carbon filtration for purification of benzodiazepine adcs |
| 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 |
| BR112015022585B1 (pt) | 2013-03-15 | 2023-04-04 | Regeneron Pharmaceuticals, Inc | Composto, composição farmacêutica, conjugado droga-anticorpo, e, uso dos mesmos |
| JP6608823B2 (ja) | 2013-08-26 | 2019-11-20 | 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 | マクロライドジアステレオマーを含む医薬組成物、その合成方法、及び治療上の使用 |
| BR112016004073A8 (pt) * | 2013-08-28 | 2018-06-12 | Stemcentrx Inc | Anticorpos criados por engenharia, conjugados de anticorpo fármaco, seu método de preparação e seu uso, composição farmacêutica e seu uso, kits, e métodos para administrar uma pirrolobenzodiazepina (pbd) a uma célula de câncer que expressa dll3 e para determinar a citotoxicidade de um conjugado de anticorpo fármaco anti-dll3 |
| BR112016004242A8 (pt) | 2013-08-28 | 2018-06-12 | Stemcentrx Inc | Métodos para conjugação sítio-específica de anticorpos e composições |
| US9993566B2 (en) | 2013-08-28 | 2018-06-12 | Abbvie Stemcentrx Llc | SEZ6 modulators and methods of use |
| EP3054985B1 (en) | 2013-10-11 | 2018-12-26 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| EP3054986B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| US10010624B2 (en) | 2013-10-11 | 2018-07-03 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
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- 2012-10-12 MX MX2014004557A patent/MX341523B/es active IP Right Grant
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- 2012-10-12 EA EA201490535A patent/EA028457B1/ru unknown
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- 2012-10-12 JP JP2014535097A patent/JP6170497B2/ja not_active Expired - Fee Related
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| EP2751111B1 (en) | 2017-04-26 |
| AU2012322934A1 (en) | 2014-05-29 |
| US20140274907A1 (en) | 2014-09-18 |
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| MX2014004557A (es) | 2015-02-12 |
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| CA2850103A1 (en) | 2013-04-18 |
| SG11201401021TA (en) | 2014-08-28 |
| BR112014008888A2 (pt) | 2017-04-18 |
| KR20140099449A (ko) | 2014-08-12 |
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