JP2016536316A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2016536316A5 JP2016536316A5 JP2016527449A JP2016527449A JP2016536316A5 JP 2016536316 A5 JP2016536316 A5 JP 2016536316A5 JP 2016527449 A JP2016527449 A JP 2016527449A JP 2016527449 A JP2016527449 A JP 2016527449A JP 2016536316 A5 JP2016536316 A5 JP 2016536316A5
- Authority
- JP
- Japan
- Prior art keywords
- protecting group
- hydroxyl protecting
- formula
- compound
- combined
- 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.)
- Granted
Links
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 62
- 150000001875 compounds Chemical class 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 26
- -1 1,3-oxazolidin-2-one-5-yl Chemical group 0.000 claims description 18
- UFNVPOGXISZXJD-JBQZKEIOSA-N eribulin Chemical compound C([C@H]1CC[C@@H]2O[C@@H]3[C@H]4O[C@@H]5C[C@](O[C@H]4[C@H]2O1)(O[C@@H]53)CC[C@@H]1O[C@H](C(C1)=C)CC1)C(=O)C[C@@H]2[C@@H](OC)[C@@H](C[C@H](O)CN)O[C@H]2C[C@@H]2C(=C)[C@H](C)C[C@H]1O2 UFNVPOGXISZXJD-JBQZKEIOSA-N 0.000 claims description 18
- 229960003649 eribulin Drugs 0.000 claims description 14
- 239000000543 intermediate Substances 0.000 claims description 13
- 229910052698 phosphorus Inorganic materials 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 150000002009 diols Chemical class 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 150000007854 aminals Chemical class 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229960000439 eribulin mesylate Drugs 0.000 claims description 3
- 238000005710 macrocyclization reaction Methods 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims 17
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 3
- 238000005865 alkene metathesis reaction Methods 0.000 claims 3
- 150000005215 alkyl ethers Chemical class 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 239000003054 catalyst Substances 0.000 claims 3
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 210000002784 stomach Anatomy 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
- VXUYPSKEYAGZCN-UHFFFAOYSA-N 2-(4-nitrobenzoyl)oxypropyl 4-nitrobenzoate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(=O)OC(C)COC(=O)C1=CC=C([N+]([O-])=O)C=C1 VXUYPSKEYAGZCN-UHFFFAOYSA-N 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- UMVMVEZHMZTUHD-UHFFFAOYSA-N DL-Propylene glycol dibenzoate Chemical compound C=1C=CC=CC=1C(=O)OC(C)COC(=O)C1=CC=CC=C1 UMVMVEZHMZTUHD-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JIIKSOMMEXFGAQ-FHWLQOOXSA-N CC(C[C@@H](O)CC[C@@H]1O[C@@H](CCCOC(=O)C(C)(C)C)CC1=C)=C=C Chemical compound CC(C[C@@H](O)CC[C@@H]1O[C@@H](CCCOC(=O)C(C)(C)C)CC1=C)=C=C JIIKSOMMEXFGAQ-FHWLQOOXSA-N 0.000 description 1
- 150000001361 allenes Chemical class 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 150000002843 nonmetals Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019181798A JP6909840B2 (ja) | 2013-11-04 | 2019-10-02 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
| JP2019213906A JP6889232B2 (ja) | 2013-11-04 | 2019-11-27 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361899697P | 2013-11-04 | 2013-11-04 | |
| US61/899,697 | 2013-11-04 | ||
| PCT/US2014/063960 WO2015066729A1 (en) | 2013-11-04 | 2014-11-04 | Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin b |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019181798A Division JP6909840B2 (ja) | 2013-11-04 | 2019-10-02 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
| JP2019213906A Division JP6889232B2 (ja) | 2013-11-04 | 2019-11-27 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016536316A JP2016536316A (ja) | 2016-11-24 |
| JP2016536316A5 true JP2016536316A5 (enExample) | 2017-12-14 |
| JP6625533B2 JP6625533B2 (ja) | 2019-12-25 |
Family
ID=53005318
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016527449A Active JP6625533B2 (ja) | 2013-11-04 | 2014-11-04 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
| JP2019181798A Active JP6909840B2 (ja) | 2013-11-04 | 2019-10-02 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
| JP2019213906A Active JP6889232B2 (ja) | 2013-11-04 | 2019-11-27 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019181798A Active JP6909840B2 (ja) | 2013-11-04 | 2019-10-02 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
| JP2019213906A Active JP6889232B2 (ja) | 2013-11-04 | 2019-11-27 | ハリコンドリンｂの類縁体の合成において有用な大環化反応および中間体 |
Country Status (12)
| Country | Link |
|---|---|
| US (5) | US9783549B2 (enExample) |
| EP (2) | EP3689881B1 (enExample) |
| JP (3) | JP6625533B2 (enExample) |
| CN (3) | CN114716453A (enExample) |
| BR (1) | BR112016009452B1 (enExample) |
| CA (1) | CA2929084C (enExample) |
| ES (1) | ES2787603T3 (enExample) |
| HU (1) | HUE049387T2 (enExample) |
| IL (4) | IL244694B (enExample) |
| RU (1) | RU2710545C2 (enExample) |
| SG (1) | SG11201603490TA (enExample) |
| WO (1) | WO2015066729A1 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5226304B2 (ja) | 2004-06-03 | 2013-07-03 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ハリコンドリンｂ類似体の調製用中間体 |
| SG10201811715YA (en) | 2007-10-03 | 2019-02-27 | Eisai R&D Man Co Ltd | Intermediates and methods for the synthesis of halichondrin b analogs |
| CA2720632C (en) | 2008-04-04 | 2016-12-20 | Eisai R&D Management Co., Ltd. | Halichondrin b analogs |
| MX2012008510A (es) | 2010-01-26 | 2012-11-21 | Eisai R&D Man Co Ltd | Derivados de furo [3, 2-b] pirano utiles en la sintesis de analogos de halicondrina b. |
| CN114716453A (zh) | 2013-11-04 | 2022-07-08 | 卫材R&D管理有限公司 | 软海绵素b的类似物合成中有用的大环化反应和中间体 |
| BR112016012237B1 (pt) | 2013-12-06 | 2023-02-07 | Eisai R&D Management Co., Ltd | Métodos úteis na síntese de análogos de halicondrina b |
| JP2017520586A (ja) | 2014-06-30 | 2017-07-27 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ハリコンドリン類似体の合成およびその使用 |
| US10344038B2 (en) | 2015-04-30 | 2019-07-09 | President And Fellows Of Harvard College | Chromium-mediated coupling and application to the synthesis of halichondrins |
| CN107849057B (zh) | 2015-05-07 | 2020-11-10 | 卫材R&D管理有限公司 | 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段 |
| WO2017064627A2 (en) * | 2015-10-14 | 2017-04-20 | Dr. Reddy's Laboratories Limited | Process for preparation of eribulin and intermediates thereof |
| MX377663B (es) * | 2016-02-12 | 2025-03-11 | Eisai R&D Man Co Ltd | Intermediarios en la sintesis de eribulina y metodos de sintesis relacionados. |
| RU2754369C2 (ru) | 2016-03-02 | 2021-09-01 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Конъюгаты антитело-лекарственное средство на основе эрибулина и способы применения |
| KR102404629B1 (ko) * | 2016-06-30 | 2022-06-02 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 할리콘드린 마크롤리드 및 그의 유사체의 합성에 유용한 프린스 반응 및 중간체 |
| JP6978758B2 (ja) | 2016-11-11 | 2021-12-08 | プレジデント アンド フェローズ オブ ハーバード カレッジ | パラジウム媒介ケトール化 |
| PL3606928T3 (pl) * | 2017-04-05 | 2023-02-06 | President And Fellows Of Harvard College | Związek makrocykliczny i jego zastosowania |
| US9938288B1 (en) | 2017-04-05 | 2018-04-10 | President And Fellows Of Harvard College | Macrocyclic compound and uses thereof |
| WO2018217894A1 (en) * | 2017-05-24 | 2018-11-29 | Eisai R&D Management Co., Ltd. | Fluorine-labelled halichondrin derivatives and related methods of synthesis |
| US11498892B2 (en) | 2017-07-06 | 2022-11-15 | President And Fellows Of Harvard College | Fe/Cu-mediated ketone synthesis |
| CN111433211B (zh) | 2017-07-06 | 2024-05-07 | 哈佛大学的校长及成员们 | 软海绵素的合成 |
| CN109694379B (zh) * | 2017-10-24 | 2020-09-11 | 江苏恒瑞医药股份有限公司 | 用于制备艾日布林的中间体及其制备方法 |
| KR102177992B1 (ko) * | 2017-11-09 | 2020-11-12 | 연성정밀화학(주) | 에리불린 메실산염의 제조 중간체 및 그의 제조방법 |
| US11407762B2 (en) | 2017-11-15 | 2022-08-09 | President And Fellows Of Harvard College | Macrocyclic compounds and uses thereof |
| US11419856B2 (en) | 2017-11-20 | 2022-08-23 | Basilea Pharmaceutica International AG | Pharmaceutical combinations for use in the treatment of neoplastic diseases |
| CN109970822B (zh) * | 2017-12-27 | 2023-03-28 | 上海科胜药物研发有限公司 | 一种合成埃格列净中间体的制备方法 |
| WO2019136145A1 (en) | 2018-01-03 | 2019-07-11 | Eisai R&D Management Co., Ltd. | Prins reaction and compounds useful in the synthesis of halichondrin macrolides and analogs thereof |
| WO2019166019A1 (zh) * | 2018-03-02 | 2019-09-06 | 北京天一绿甫医药科技有限公司 | 吡喃稠环类化合物、其制备方法和用途 |
| WO2019211877A1 (en) * | 2018-05-03 | 2019-11-07 | Cipla Limited | Process for the preparation of macrocyclic ketone analogs of halichondrin b |
| WO2020016847A2 (en) * | 2018-07-20 | 2020-01-23 | Dr. Reddy’S Laboratories Limited | Purification process for preparation of eribulin and intermediates thereof |
| US11447499B2 (en) * | 2019-06-14 | 2022-09-20 | Rk Pharma Inc. | Process for the preparation of eribulin mesylate intermediate |
| CN110684036B (zh) * | 2019-11-22 | 2022-04-12 | 江苏慧聚药业股份有限公司 | 一条制备甲磺酸艾日布林的方法 |
| WO2023144733A1 (en) * | 2022-01-26 | 2023-08-03 | Simon Fraser University | Compounds and processes for the preparation of eribulin |
| CN119585437A (zh) * | 2022-07-29 | 2025-03-07 | 上海皓元医药股份有限公司 | 一种艾日布林中间体的制备方法 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4107206A (en) | 1974-04-08 | 1978-08-15 | Akzona Incorporated | Benzo-bicyclononene- derivatives |
| SU652180A1 (ru) | 1975-12-16 | 1979-03-15 | Краснодарский политехнический институт | 1(Фурил-2,)-2-(2-,, формилфурил-5,, ) этилен или его метильное производное как промежуточный продукт дл синтеза фуран-2,5-дикарбоновой кислоты и способ его получени |
| US5338865A (en) | 1992-03-12 | 1994-08-16 | President And Fellows Of Harvard College | Synthesis of halichondrin B and norhalichondrin B |
| US5436238A (en) | 1992-03-12 | 1995-07-25 | President And Fellows Of Harvard College | Halichondrins and related compounds |
| GB9206244D0 (en) | 1992-03-23 | 1992-05-06 | Pharma Mar Sa | Cytotoxic compound from a marine sponge |
| TW255880B (enExample) | 1992-09-09 | 1995-09-01 | Hoechst Ag | |
| AU4255697A (en) | 1996-09-06 | 1998-03-26 | Eli Lilly And Company | Catalytic selective sulfonylation process |
| US6870058B2 (en) | 1996-12-03 | 2005-03-22 | The Trustees Of The University Of Pennsylvania | Compounds which mimic the chemical and biological properties of discodermolide |
| EP2272840B1 (en) | 1998-06-17 | 2012-08-22 | Eisai R&D Management Co., Ltd. | Intermediate compound for the preparation of halichondrin analogs |
| US6653341B1 (en) | 1998-06-17 | 2003-11-25 | Eisai Co., Ltd. | Methods and compositions for use in treating cancer |
| US8097648B2 (en) | 1998-06-17 | 2012-01-17 | Eisai R&D Management Co., Ltd. | Methods and compositions for use in treating cancer |
| DE10106647A1 (de) | 2001-02-12 | 2002-08-22 | Univ Hannover | Ratjadon-Derivate zum Hemmen des Zellwachstums |
| CN1993342A (zh) * | 2004-06-03 | 2007-07-04 | 卫材株式会社 | 用于制备软海绵素b的中间体 |
| JP5226304B2 (ja) | 2004-06-03 | 2013-07-03 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ハリコンドリンｂ類似体の調製用中間体 |
| US20060045846A1 (en) * | 2004-08-30 | 2006-03-02 | Horstmann Thomas E | Reagents and methods for labeling terminal olefins |
| JP2008522623A (ja) | 2004-12-09 | 2008-07-03 | エーザイ株式会社 | ハリコンドリンｂアナログを使用した癌治療でのチューブリンアイソタイプのスクリーニング |
| JP2009510005A (ja) | 2005-09-26 | 2009-03-12 | シムライズ・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング・ウント・コンパニー・コマンジツト・ゲゼルシヤフト | 分子内プリンス反応および該反応に適する触媒 |
| WO2008010776A1 (en) * | 2006-07-21 | 2008-01-24 | Agency For Science, Technology And Research | Aigialomycin d and derivatives thereof and their use in treating cancer or malaria or a microbial infection |
| JPWO2009014105A1 (ja) | 2007-07-20 | 2010-10-07 | 株式会社山田養蜂場本社 | 新規カルボン酸およびそれを有効成分とする抗うつ用組成物 |
| SG10201811715YA (en) | 2007-10-03 | 2019-02-27 | Eisai R&D Man Co Ltd | Intermediates and methods for the synthesis of halichondrin b analogs |
| EP2220094A1 (en) | 2007-11-16 | 2010-08-25 | Eisai R&D Management Co., Ltd. | Novel intermediate for halichondrin b analog synthesis and novel desulfonylation reaction used for the intermediate |
| CA2720632C (en) | 2008-04-04 | 2016-12-20 | Eisai R&D Management Co., Ltd. | Halichondrin b analogs |
| JP5371091B2 (ja) | 2009-01-23 | 2013-12-18 | 三菱レイヨン株式会社 | モノスルホン酸エステルの製造方法 |
| MX2012008510A (es) | 2010-01-26 | 2012-11-21 | Eisai R&D Man Co Ltd | Derivados de furo [3, 2-b] pirano utiles en la sintesis de analogos de halicondrina b. |
| WO2012147900A1 (en) | 2011-04-28 | 2012-11-01 | Eisai R&D Management Co., Ltd. | Microreactor process for halichondrin b analog synthesis |
| JP2015500210A (ja) * | 2011-11-30 | 2015-01-05 | アルフォラ リサーチ インコーポレイテッドＡｌｐｈｏｒａ Ｒｅｓｅａｒｃｈ Ｉｎｃ． | （３ｒ）−２，４−ジ−脱離基−３−メチルブタ−１−エンの調製方法 |
| CN104334562A (zh) | 2012-03-30 | 2015-02-04 | 阿方拉研究股份有限公司 | 用于制备软海绵素b的大环c1-酮类似物的合成方法及其中有用的中间体 |
| EP3016957A4 (en) | 2013-07-03 | 2016-11-30 | Alphora Res Inc | SYNTHETIC METHOD FOR THE PRODUCTION OF CYCLIC C1-KETO ANALOGUE OF HALICHONDRIN B AND USEFUL INTERMEDIATE PRODUCTS, INCLUDING INTERMEDIATE PRODUCTS WITH -SO2- (P-TOLYL) GROUPS |
| CN114716453A (zh) | 2013-11-04 | 2022-07-08 | 卫材R&D管理有限公司 | 软海绵素b的类似物合成中有用的大环化反应和中间体 |
| BR112016012237B1 (pt) | 2013-12-06 | 2023-02-07 | Eisai R&D Management Co., Ltd | Métodos úteis na síntese de análogos de halicondrina b |
| WO2016038624A1 (en) | 2014-09-09 | 2016-03-17 | Cipla Limited | "process for the preparation of macrocyclic ketone analogs of halichondrin b or pharmaceutically acceptable salts and intermediates thereof" |
| US10344038B2 (en) * | 2015-04-30 | 2019-07-09 | President And Fellows Of Harvard College | Chromium-mediated coupling and application to the synthesis of halichondrins |
| CN107849057B (zh) | 2015-05-07 | 2020-11-10 | 卫材R&D管理有限公司 | 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段 |
| MX377663B (es) | 2016-02-12 | 2025-03-11 | Eisai R&D Man Co Ltd | Intermediarios en la sintesis de eribulina y metodos de sintesis relacionados. |
| KR102404629B1 (ko) | 2016-06-30 | 2022-06-02 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 할리콘드린 마크롤리드 및 그의 유사체의 합성에 유용한 프린스 반응 및 중간체 |
| US20180009825A1 (en) * | 2016-07-06 | 2018-01-11 | Apicore Us Llc | Methods of making eribulin mesylate |
| WO2018217894A1 (en) | 2017-05-24 | 2018-11-29 | Eisai R&D Management Co., Ltd. | Fluorine-labelled halichondrin derivatives and related methods of synthesis |
| WO2019136145A1 (en) * | 2018-01-03 | 2019-07-11 | Eisai R&D Management Co., Ltd. | Prins reaction and compounds useful in the synthesis of halichondrin macrolides and analogs thereof |
-
2014
- 2014-11-04 CN CN202210377346.8A patent/CN114716453A/zh active Pending
- 2014-11-04 EP EP20156829.2A patent/EP3689881B1/en active Active
- 2014-11-04 US US15/033,970 patent/US9783549B2/en active Active
- 2014-11-04 WO PCT/US2014/063960 patent/WO2015066729A1/en not_active Ceased
- 2014-11-04 JP JP2016527449A patent/JP6625533B2/ja active Active
- 2014-11-04 ES ES14858240T patent/ES2787603T3/es active Active
- 2014-11-04 RU RU2016121648A patent/RU2710545C2/ru active
- 2014-11-04 CA CA2929084A patent/CA2929084C/en active Active
- 2014-11-04 EP EP14858240.6A patent/EP3066102B1/en active Active
- 2014-11-04 HU HUE14858240A patent/HUE049387T2/hu unknown
- 2014-11-04 CN CN201480059909.2A patent/CN105683198B/zh active Active
- 2014-11-04 CN CN201910122043.XA patent/CN109942560B/zh active Active
- 2014-11-04 BR BR112016009452-2A patent/BR112016009452B1/pt active IP Right Grant
- 2014-11-04 SG SG11201603490TA patent/SG11201603490TA/en unknown
-
2016
- 2016-03-21 IL IL244694A patent/IL244694B/en active IP Right Grant
-
2017
- 2017-09-18 US US15/707,412 patent/US10221189B2/en active Active
-
2019
- 2019-01-14 US US16/246,999 patent/US10611773B2/en active Active
- 2019-07-09 IL IL267936A patent/IL267936B/en active IP Right Grant
- 2019-10-02 JP JP2019181798A patent/JP6909840B2/ja active Active
- 2019-11-27 JP JP2019213906A patent/JP6889232B2/ja active Active
-
2020
- 2020-03-30 US US16/833,923 patent/US10934307B2/en active Active
- 2020-06-09 IL IL275240A patent/IL275240B/en unknown
-
2021
- 2021-03-01 US US17/188,819 patent/US11643418B2/en active Active
- 2021-11-28 IL IL288468A patent/IL288468B2/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2016536316A5 (enExample) | ||
| JP6432452B2 (ja) | 縮合複素環化合物の製造方法 | |
| JP2013533291A5 (enExample) | ||
| TWI864071B (zh) | 2-羥環烷-1-胺甲醯基衍生物 | |
| CA2882386C (en) | Substituted pyrido[1,2-a]pyrazines and their use in the treatment of neurodegenerative and/or neurological disorders | |
| JP7771205B2 (ja) | トリアゾリル－メチル置換アルファ－ｄ－ガラクトピラノシド誘導体 | |
| JP2017518959A5 (enExample) | ||
| WO1999007692A2 (de) | Neue epothilon-derivate, verfahren zu deren herstellung und ihre pharmazeutische verwendung | |
| IL198880A (en) | Indazolil's affluent history, their pharmaceutical preparations, their process and their use in the preparation of medications for the treatment of infectious diseases, asthma or copd | |
| JP2023545046A (ja) | アルファ－ｄ－ガラクトピラノシドのスピロ誘導体 | |
| Yoshimitsu et al. | Synthesis of pachastrissamine (jaspine B) and its derivatives by the late-stage introduction of the C-2 alkyl side-chains using olefin cross metathesis | |
| KR20230145111A (ko) | 히드록시헤테로시클로알칸-카르바모일 유도체 | |
| JP2023547241A (ja) | ガレクチン－３を阻害する２－ヒドロキシシクロアルカン－１－カルバモイル誘導体 | |
| JP2024530111A (ja) | アフィカムテンを調製するための工程 | |
| WO2014049133A1 (en) | New positive allosteric modulators of nicotinic acetylcholine receptor | |
| JP2018506541A (ja) | Ｎｅｐ阻害剤を調製するための方法および中間体 | |
| AU2007320029A1 (en) | Thrombin receptor antagonists based on the modified tricyclic unit of himbacine | |
| CN107513050B (zh) | 一种烯酸溴内酯化的制备方法 | |
| Zeng et al. | Practical synthesis of trans-dihydroxybutyrolactols as chiral C 4 building blocks and their application to the synthesis of polyhydroxylated alkaloids | |
| JP5960130B2 (ja) | テセタキセルおよび関連化合物ならびに対応する合成中間体の調製 | |
| CN101076518A (zh) | 5－氨基－4－羟基－2－异丙基－7－[4－甲氧基－3－(3－甲氧基丙氧基)苄基]－8－甲基－壬酰胺 | |
| TWI905393B (zh) | 經三唑基-甲基取代的α-D-吡喃半乳糖苷衍生物 | |
| JP2002501064A (ja) | 複素芳香環縮合シクロペンテノピリジン誘導体 | |
| CN107353266A (zh) | 一种烯酸溴内酯化的制备方法 | |
| JP2024538727A (ja) | マボリキサフォルの合成およびその中間体 |