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 PDFInfo
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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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- 0 *C(CC(*)=C1)N1C(c1cc(*)c(*)c(*)c1N*)=O Chemical compound *C(CC(*)=C1)N1C(c1cc(*)c(*)c(*)c1N*)=O 0.000 description 6
- JXORKYUYGAUCBT-VOTSOKGWSA-N CC1(C)OB(/C=C/C(C)=O)OC1(C)C Chemical compound CC1(C)OB(/C=C/C(C)=O)OC1(C)C JXORKYUYGAUCBT-VOTSOKGWSA-N 0.000 description 1
- CUXVXWBQMSPDNN-VOTSOKGWSA-N CC1(C)O[O](/C=C/C(OC)=O)OC1(C)C Chemical compound CC1(C)O[O](/C=C/C(OC)=O)OC1(C)C CUXVXWBQMSPDNN-VOTSOKGWSA-N 0.000 description 1
- UVRSGWXFJXTLPQ-UHFFFAOYSA-N NC[O-]CCOCCNC(CI)=O Chemical compound NC[O-]CCOCCNC(CI)=O UVRSGWXFJXTLPQ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic 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
- C07D207/18—Heterocyclic 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
- C07D207/20—Heterocyclic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic 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
- C07D207/18—Heterocyclic 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
- C07D207/22—Heterocyclic 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
- C07D207/24—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic 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
- C07D207/18—Heterocyclic 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
- C07D207/22—Heterocyclic 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- Y—GENERAL 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design 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)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104011018A CN104011018A (zh) | 2014-08-27 |
| CN104011018B true CN104011018B (zh) | 2016-12-14 |
Family
ID=47019019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280061966.5A Active CN104011018B (zh) | 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 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9102704B2 (https=) |
| EP (1) | EP2751076B1 (https=) |
| JP (1) | JP6166728B2 (https=) |
| CN (1) | CN104011018B (https=) |
| AU (1) | AU2012322933B2 (https=) |
| BR (1) | BR112014009070B1 (https=) |
| CA (1) | CA2850096C (https=) |
| EA (1) | EA029046B1 (https=) |
| WO (1) | WO2013053872A1 (https=) |
Families Citing this family (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CA2795349C (en) | 2010-04-15 | 2016-11-29 | Seattle Genetics, Inc. | Targeted pyrrolobenzodiazepine conjugates |
| SG11201400770SA (en) | 2011-09-20 | 2014-04-28 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
| AU2012322932B2 (en) | 2011-10-14 | 2016-11-10 | Medimmune Limited | Pyrrolobenzodiazepines |
| CA2850373C (en) | 2011-10-14 | 2019-07-16 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and 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 |
| 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 |
| ES2680153T3 (es) | 2012-10-12 | 2018-09-04 | Adc Therapeutics Sa | Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas |
| 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 |
| EP2906296B1 (en) | 2012-10-12 | 2018-03-21 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| HRP20190366T1 (hr) | 2012-10-12 | 2019-04-19 | Medimmune Limited | Pirolobenzodiazepini i njihovi konjugati |
| RS57694B1 (sr) | 2012-10-12 | 2018-11-30 | Adc Therapeutics Sa | Pirolobenzodiazepin - anti-psma konjugati antitela |
| EP2906249B1 (en) | 2012-10-12 | 2018-06-27 | MedImmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| MX338711B (es) | 2012-10-12 | 2016-04-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| HRP20182129T1 (hr) | 2012-10-12 | 2019-02-08 | Adc Therapeutics Sa | Konjugati protutijelo - pirolobenzodiazepin |
| EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| 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 |
| JP6847388B2 (ja) | 2013-03-15 | 2021-03-31 | 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 | 生物活性分子、そのコンジュゲート、及び治療用途 |
| BR112016004023A2 (pt) | 2013-08-26 | 2022-11-16 | Regeneron Pharma | Composição, métodos para preparar uma composição e para tratar uma doença, e, composto |
| 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 |
| EP3054983B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| JP6632984B2 (ja) | 2014-03-11 | 2020-01-22 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 抗ＥＧＦＲｖＩＩＩ抗体およびその使用 |
| 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 |
| 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 |
| BR112017020149A8 (pt) | 2015-03-27 | 2023-05-02 | Regeneron Pharma | Derivados de maitansinoide, conjugados dos mesmos e métodos de uso |
| 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 |
| IL296285A (en) | 2015-07-06 | 2022-11-01 | Regeneron Pharma | Multispecific antigen-binding molecules and uses thereof |
| 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 |
| BR112018014759B1 (pt) | 2016-01-25 | 2024-02-27 | Regeneron Pharmaceuticals, Inc | Compostos derivados de maitasinoide e seus conjugados, composição compreendendo os mesmos, seus métodos de fabricação e uso |
| 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 |
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| GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| EP3478324A1 (en) | 2016-07-01 | 2019-05-08 | GlaxoSmithKline Intellectual Property (No.2) Limited | Antibody-drug conjugates and therapeutic methods using the same |
| JP7066690B2 (ja) | 2016-09-23 | 2022-05-13 | 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 | 抗ｍｕｃ１６（ムチン１６）抗体 |
| MY199468A (en) | 2016-09-23 | 2023-10-31 | Regeneron Pharma | 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 |
| ES3046537T3 (en) | 2016-11-08 | 2025-12-02 | Regeneron Pharma | 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 |
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| 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 |
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| KR20200007905A (ko) | 2017-05-18 | 2020-01-22 | 리제너론 파마슈티칼스 인코포레이티드 | 사이클로덱스트린 단백질 약물 접합체 |
| DK3635009T3 (da) | 2017-06-07 | 2026-03-30 | Regeneron Pharma | Sammensætninger og fremgangsmåder til internalisering af enzymer |
| 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 |
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| CN118955710A (zh) | 2018-05-09 | 2024-11-15 | 里珍纳龙药品有限公司 | 抗msr1抗体及其使用方法 |
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| IL283313B2 (en) | 2018-11-20 | 2025-08-01 | Regeneron Pharma | Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof for use as lxr agonists |
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| EA029046B1 (ru) | 2018-02-28 |
| EP2751076A1 (en) | 2014-07-09 |
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| BR112014009070A2 (pt) | 2017-04-18 |
| JP2015502331A (ja) | 2015-01-22 |
| BR112014009070B1 (pt) | 2021-11-23 |
| AU2012322933B2 (en) | 2017-02-02 |
| CN104011018A (zh) | 2014-08-27 |
| WO2013053872A1 (en) | 2013-04-18 |
| EP2751076B1 (en) | 2018-04-25 |
| AU2012322933A1 (en) | 2014-05-29 |
| US9102704B2 (en) | 2015-08-11 |
| US20140275522A1 (en) | 2014-09-18 |
| CA2850096A1 (en) | 2013-04-18 |
| CA2850096C (en) | 2018-07-03 |
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