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HRP20150543T1 - Međuprodukti za pripravu halikondrina b - Google Patents

Međuprodukti za pripravu halikondrina b Download PDF

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HRP20150543T1
HRP20150543T1 HRP20150543TT HRP20150543T HRP20150543T1 HR P20150543 T1 HRP20150543 T1 HR P20150543T1 HR P20150543T T HRP20150543T T HR P20150543TT HR P20150543 T HRP20150543 T HR P20150543T HR P20150543 T1 HRP20150543 T1 HR P20150543T1
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Farid Benayoud
Trevor Lee Calkins
Charles E. Chase
William Christ
Francis G. Fang
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Eisai R&D Management Co., Ltd.
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Publication of HRP20150543T1 publication Critical patent/HRP20150543T1/hr

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    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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    • C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
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    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings 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
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    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Compounds Of Unknown Constitution (AREA)

Claims (19)

1. Spoj s formulom A, B, ili C: [image] naznačen time da: ---- označava jednostruku ili dvostruku vezu; n je 1, 2, ili 3; svaki od PG5 i PG6 je neovisno pogodna hidroksil zaštitna skupina, koja zajedno s atomom kisika na koji je spojena, je odabrana od estera, silil etera, alkil etera, arilalkil etera, te alkoksialkil etera, ili PG5 i PG6 su uzeti zajedno tako da tvore zaštitnu skupinu cikličkog diola, koja je uzeta zajedno s atomima kisika na koje su vezani, odabrana od cikličkog acetala, cikličkog ketala, derivata sililena, cikličkog karbonata, te cikličkog boronata; W je CH-A ili C(O); A je C1-6 alifatska skupina, pri čemu A je proizvoljno supstituiran s jednom ili više Q1 skupina; svaki Q1 je neovisno odabran od cijano, halo, azido, okso, OR, SR, SO2R, OSO2R, N(R)2, NR(CO)R, NR(CO)(CO)R, NR(CO)N(R)2, NR(CO)OR, (CO)OR, O(CO)R, (CO)N(R)2, O(CO)N(R)2, ili OPG1, pri čemu PG1 je pogodna hidroksil zaštitna skupina, koja zajedno s atomom kisika na koji je spojena, je odabrana od estera, silil etera, alkil etera, arilalkil etera, te alkoksialkil etera, te pri čemu: proizvoljno dva Q1 su na A i uzeti su zajedno tako da tvore 3-8 člani zasićeni, djelomično nezasićeni, ili arilni prsten koji ima 0-4 heteroatoma neovisno odabrana od dušika, kisika, ili sumpora; svaki R je neovisno odabran od vodika ili proizvoljno supstituirane skupine odabrane od C1-6 alifatskog, 5-10 članog zasićenog, djelomično nezasićenog ili arilnog karbocikličkog prstena, ili 4-10 članog zasićenog, djelomično nezasićenog ili arilnog prstena koji ima 0-4 heteroatoma neovisno odabrana od dušika, kisika, ili sumpora, pri čemu: kada je Q1 neovisno odabran od N(R)2, NR(CO)N(R)2, (CO)N(R)2, i O(CO)N(R)2, dvije R skupine na istom atomu dušika su proizvoljno uzete zajedno s navedenim atomom dušika tako da tvore 3-8 člani zasićeni, djelomično nezasićeni, ili arilni prsten koji ima 1-4 heteroatoma neovisno odabrana od dušika, kisika, ili sumpora; te pri čemu XB je O, i RB je TMS; XB je H i OH, i RB je TMS; ili XB je H, OAc, i RB je Ac; i R1 je -CH2CO2R2, pri čemu R2 je alkil.
2. Spoj prema zahtjevu 1 naznačen time da ima formulu: [image]
3. Spoj prema zahtjevu 2 naznačen time da ima formulu: [image]
4. Spoj prema zahtjevu 1 naznačen time da ima formulu: [image]
5. Spoj prema zahtjevu 1 naznačen time da ima formulu: [image]
6. Spoj prema zahtjevu 1 naznačen time da ima formulu: [image]
7. Spoj prema zahtjevu 1 naznačen time da ima formulu: [image]
8. Spoj prema zahtjevu 1, naznačen time da spoj je prema formuli C, i R2 je metil.
9. Spoj koji ima formulu F-2: [image] naznačen time da: svako --- je neovisno jednostruka ili dvostruka veza, pod uvjetom da obje --- skupine nisu istovremeno dvostruka veza; LG1 je prikladna izlazna skupina odabrana iz skupine koja sadrži sulfoniloksi, proizvoljno supstituiran alkilsulfoniloksi, proizvoljno supstituiran alkenilsulfoniloksi, proizvoljno supstituiran arilsulfoniloksi, te halogen; X je -OSO2(Ry); Ry je C1-6 alifatski ili 5-7 člani zasićeni, djelomično nezasićeni, ili potpuno nezasićeni prsten, pri čemu Ry je proizvoljno supstituiran sa do 3 skupine odabrane od halogena, R, NO2 CN, OR, SR, ili N(R)2; svaki R je neovisno vodik, C1-4 haloalifatski, ili C1-4 alifatski; i PG3 je pogodna hidroksil zaštitna skupina, koja je zajedno s atomom kisika na koji je spojena, odabrana od estera, silil etera, alkil etera, arilalkil etera, te alkoksialkil etera.
10. Spoj prema zahtjevu 9 naznačen time da ima formulu: [image]
11. Spoj prema zahtjevu 9 naznačen time da ima formulu: [image]
12. Spoj naznačen time da ima formulu: [image]
13. Spoj naznačen time da ima formulu: [image]
14. Spoj prema zahtjevu 13 naznačen time da ima formulu: [image]
15. Spoj naznačen time da ima formulu: [image]
16. Spoj prema zahtjevu 15 naznačen time da ima formulu: [image]
17. Postupak za pripravu spoja s formulom B-1939 [image] naznačen time da se spoj pripravlja preko spoja prema bilo kojem zahtjevu 1-8.
18. Postupak za pripravu spoja s formulom B-1939 [image] naznačen time da se spoj pripravlja preko spoja prema bilo kojem zahtjevu 9-11.
19. Postupak za pripravu spoja s formulom B-1939 [image] naznačen time da se spoj pripravlja preko spoja prema bilo kojem zahtjevu 12-16.
HRP20150543TT 2004-06-03 2015-05-20 Međuprodukti za pripravu halikondrina b HRP20150543T1 (hr)

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US57664204P 2004-06-03 2004-06-03
US62676904P 2004-11-10 2004-11-10
US66330005P 2005-03-18 2005-03-18
EP12178696.6A EP2522663B1 (en) 2004-06-03 2005-06-03 Intermediates for the preparation of halichondrin B

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US (10) US7982060B2 (hr)
EP (4) EP1771431A1 (hr)
JP (5) JP5226304B2 (hr)
KR (1) KR101434673B1 (hr)
CN (2) CN101899026B (hr)
AU (1) AU2005250487B2 (hr)
CA (3) CA2567984C (hr)
ES (1) ES2748200T3 (hr)
HR (1) HRP20150543T1 (hr)
HU (1) HUE046436T2 (hr)
IL (5) IL180252A (hr)
PL (1) PL2522663T3 (hr)
RS (1) RS54054B1 (hr)
SI (1) SI2522663T1 (hr)
WO (1) WO2005118565A1 (hr)

Families Citing this family (71)

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Publication number Priority date Publication date Assignee Title
HU227912B1 (en) * 1998-06-17 2012-05-29 Eisai R & D Man Co Halichondrin analogs and methods of their use and preparation
CA2567984C (en) 2004-06-03 2014-05-20 Eisai Co., Ltd. Intermediates for the preparation of analogs of halichondrin b
EP2578576B9 (en) 2007-10-03 2016-09-14 Eisai R&D Management Co., Ltd. Intermediates for the synthesis of halichondrin B analogs
JP5134686B2 (ja) * 2007-11-16 2013-01-30 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アナログ合成のための新規な中間体及び前記中間体に用いるための新規な脱スルホニル化反応
BRPI0911269A2 (pt) * 2008-04-04 2015-09-29 Eisai R&D Man Co Ltd análogos de halicondrina b
SI2415470T1 (sl) 2009-03-30 2016-12-30 Eisai R&D Management Co., Ltd. Liposomski sestavek
JP5556811B2 (ja) * 2009-04-14 2014-07-23 日産化学工業株式会社 テトラヒドロピラン化合物の製造方法
SG182612A1 (en) 2010-01-26 2012-08-30 Eisai R&D Man Co Ltd Furo [3, 2 -b] pyrane derivatives useful in the synthesis of halichondrin b analogs
WO2012147900A1 (en) 2011-04-28 2012-11-01 Eisai R&D Management Co., Ltd. Microreactor process for halichondrin b analog synthesis
WO2013053102A1 (en) * 2011-10-11 2013-04-18 Givaudan Sa Improvements in or relating to organic compounds
US9181152B2 (en) 2011-11-30 2015-11-10 Alphora Research Inc. Process for preparation of (3R)-2,4-di-leaving group-3-methylbut-1-ene
JP2015501818A (ja) 2011-12-16 2015-01-19 アルフォラ リサーチ インコーポレイテッドＡｌｐｈｏｒａ Ｒｅｓｅａｒｃｈ Ｉｎｃ． ３−（（２ｓ，５ｓ）−４−メチレン−５−（３−オキソプロピル）テトラヒドロフラン−２−イル）プロパノール誘導体およびそれらの有用な中間体を調製する方法
EP2797945B1 (en) * 2011-12-29 2016-03-16 Alphora Research Inc. 2-((2s,3s,4r,5r)-5-((s)-3-amino-2-hydroxyprop-1-yl)-4-methoxy-3-(phenylsulfonylmethyl)tetrahydrofuran-2-yl)acetaldehyde derivatives and process for their preparation
WO2013142999A1 (en) 2012-03-30 2013-10-03 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein
MX2015007185A (es) 2012-12-04 2017-09-05 Eisai R&D Man Co Ltd Uso de eribulina en el tratamiento de cancer de pecho.
RU2672585C2 (ru) * 2013-06-26 2018-11-16 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Применение эрибулина и ленватиниба в качестве комбинированной терапии для лечения рака
AU2014286880B2 (en) 2013-07-03 2017-12-14 Sandoz Ag Synthetic process for preparation of macrocyclic C1-keto analogs of Halichondrin B and intermediates useful therein including intermediates containing -SO2-(p-TOLYL) groups
JP6625533B2 (ja) * 2013-11-04 2019-12-25 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
RU2676486C1 (ru) 2013-12-06 2018-12-29 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Способы, предназначенные для синтеза аналогов галихондрина b
TW201617326A (zh) 2014-03-06 2016-05-16 Ａｌｐｈｏｒａ研發股份有限公司 （ｓ）－１－（（２ｒ，３ｒ，４ｓ，５ｓ）－５－烯丙－３－甲氧－４－（對甲苯磺醯甲基）四氫呋喃－２－基）－３－氨基丙－２－醇之結晶衍生物
CN106413705A (zh) 2014-05-28 2017-02-15 卫材R&D管理有限公司 艾日布林在治疗癌症中的用途
US10556910B2 (en) 2014-06-30 2020-02-11 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses thereof
EP3191479B1 (en) 2014-09-09 2020-04-08 Cipla Limited "process for the preparation of macrocyclic ketone analogs of halichondrin b or pharmaceutically acceptable salts and intermediates thereof"
WO2016140717A1 (en) 2015-03-04 2016-09-09 Merck Sharp & Dohme Corp. Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer
SG11201706872SA (en) 2015-03-04 2017-09-28 Merck Sharp & Dohme Combination of a pd-1 antagonist and eribulin for treating cancer
US10344038B2 (en) 2015-04-30 2019-07-09 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
RU2020141025A (ru) * 2015-05-07 2020-12-28 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Реакции макроциклизации и промежуточные соединения и другие фрагменты, полезные в синтезе макролидов галихондринов
KR101777634B1 (ko) 2016-01-18 2017-09-12 연성정밀화학(주) 3-((2s,5s)-4-메틸렌-5-(3-옥소프로필)테트라히드로퓨란-2-일)프로판올 유도체의 제조방법 및 이를 위한 중간체
SG11201806133UA (en) 2016-02-12 2018-08-30 Eisai R&D Man Co Ltd Intermediates in the synthesis of eribulin and related methods of synthesis
CN114191563A (zh) 2016-03-02 2022-03-18 卫材研究发展管理有限公司 基于艾日布林的抗体-药物偶联物和使用方法
EP3449921B1 (en) 2016-04-28 2023-05-31 Eisai R&D Management Co., Ltd. Eribulin for inhibiting tumor growth
KR20190009326A (ko) * 2016-05-26 2019-01-28 닥터 레디스 레보러터리즈 리미티드 에리불린 및 그의 중간체의 제조방법
SG11201811671XA (en) * 2016-06-30 2019-01-30 Eisai R&D Man Co Ltd Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof
SG11201902974PA (en) 2016-10-14 2019-05-30 Merck Sharp & Dohme Combination of a pd-1 antagonist and eribulin for treating urothelial cancer
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
BR112019010494A2 (pt) 2016-11-23 2019-09-17 Dr Reddys Laboratories Ltd processo para a preparação de eribulina e intermediários do mesmo
US10865212B2 (en) 2017-01-02 2020-12-15 Yonsung Fine Chemical Co.. Ltd. Intermediate for preparing eribulin mesylate and process for preparing the same
KR101880939B1 (ko) * 2017-01-02 2018-08-17 연성정밀화학(주) 에리불린 메실산염의 제조 중간체 및 그의 제조방법
MX2019011982A (es) * 2017-04-05 2019-11-08 Harvard College Compuesto macrociclico y sus usos.
US9938288B1 (en) 2017-04-05 2018-04-10 President And Fellows Of Harvard College Macrocyclic compound and uses thereof
CN108948064B (zh) * 2017-05-17 2021-02-02 上海时莱生物技术有限公司 一种艾日布林中间体及其制备方法
US11498892B2 (en) 2017-07-06 2022-11-15 President And Fellows Of Harvard College Fe/Cu-mediated ketone synthesis
MX2020000142A (es) 2017-07-06 2020-07-22 Harvard College Sintesis de halicondrinas.
US20190046513A1 (en) 2017-08-10 2019-02-14 Huya Bioscience International, Llc Combination therapies of hdac inhibitors and tubulin inhibitors
CN111328328B (zh) * 2017-11-09 2023-05-23 研成精密化学株式会社 用于制备甲磺酸艾日布林的中间体及其制备方法
US11407762B2 (en) 2017-11-15 2022-08-09 President And Fellows Of Harvard College Macrocyclic compounds and uses thereof
EP3713565A1 (en) 2017-11-20 2020-09-30 Basilea Pharmaceutica International AG Pharmaceutical combinations for use in the treatment of neoplastic diseases
WO2019102490A1 (en) 2017-11-21 2019-05-31 Natco Pharma Limited Intermediates for the preparation of eribulin thereof
CN107973804B (zh) * 2017-11-29 2020-07-03 戊言医药科技（上海）有限公司 艾瑞布林中间体的合成方法
JP7469226B2 (ja) 2018-01-03 2024-04-16 エーザイ・アール・アンド・ディー・マネジメント株式会社 ハリコンドリンマクロライドとそのアナログの合成に有用なプリンス反応及び化合物
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
WO2020008382A1 (en) * 2018-07-04 2020-01-09 Dr. Reddy’S Laboratories Limited Process for preparation of eribulin and intermediates thereof
CN111285894B (zh) * 2018-12-10 2021-03-05 北京天一绿甫医药科技有限公司 用于制备软海绵素类化合物的中间体及其制备方法
CN111454277A (zh) * 2019-01-21 2020-07-28 上海茂晟康慧科技有限公司 一种艾日布林中间体er806047的合成方法
CN116159601B (zh) * 2019-03-15 2024-07-23 博瑞生物医药（苏州）股份有限公司 艾日布林中间体及其制备方法
US11447499B2 (en) 2019-06-14 2022-09-20 Rk Pharma Inc. Process for the preparation of eribulin mesylate intermediate
JP7574232B2 (ja) 2019-06-21 2024-10-28 カウンスィル オブ サイエンティフィック アンド インダストリアル リサーチ ホモプロパルギルアルコールを調製するための化学酵素的プロセス
US12036204B2 (en) 2019-07-26 2024-07-16 Eisai R&D Management Co., Ltd. Pharmaceutical composition for treating tumor
US11083705B2 (en) 2019-07-26 2021-08-10 Eisai R&D Management Co., Ltd. Pharmaceutical composition for treating tumor
CN112409302A (zh) * 2019-08-22 2021-02-26 上海茂晟康慧科技有限公司 一种艾日布林中间体er806060的合成方法
CN113024589A (zh) * 2019-12-09 2021-06-25 南通诺泰生物医药技术有限公司 艾日布林及其中间体的制备方法
CN113024576B (zh) * 2019-12-09 2024-03-29 南通诺泰生物医药技术有限公司 艾日布林及其中间体的制备方法
CN113121555B (zh) * 2020-01-16 2024-03-08 南通诺泰生物医药技术有限公司 通过微通道反应器制备艾日布林中间体的方法
CN113135876B (zh) * 2020-01-16 2024-05-17 南通诺泰生物医药技术有限公司 艾日布林及其中间体的制备方法
CN113549101A (zh) * 2020-04-26 2021-10-26 博瑞生物医药（苏州）股份有限公司 艾日布林及其中间体的制备方法
CA3098164A1 (en) * 2020-11-05 2022-05-05 Eurofins Cdmo Alphora Inc. Process for preparation of advanced intermediate for eribulin synthesys
IL279168B (en) * 2020-12-02 2022-04-01 Finetech Pharmaceutical Ltd A process for the preparation of eribulin
CN114213449A (zh) * 2021-12-28 2022-03-22 南京格亚医药科技有限公司 一种甲磺酸艾日布林关键中间体异构体的制备方法
CN114409617A (zh) * 2021-12-28 2022-04-29 南京格亚医药科技有限公司 一种甲磺酸艾日布林关键中间体异构体的制备方法
WO2023157015A1 (en) * 2022-02-17 2023-08-24 Natco Pharma Limited An improved process for the preparation of eribulin intermediates

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5436238A (en) 1992-03-12 1995-07-25 President And Fellows Of Harvard College Halichondrins and related compounds
US5338865A (en) 1992-03-12 1994-08-16 President And Fellows Of Harvard College Synthesis of halichondrin B and norhalichondrin B
GB9206244D0 (en) 1992-03-23 1992-05-06 Pharma Mar Sa Cytotoxic compound from a marine sponge
TW255880B (hr) * 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
US6653341B1 (en) * 1998-06-17 2003-11-25 Eisai Co., Ltd. Methods and compositions for use in treating cancer
HU227912B1 (en) 1998-06-17 2012-05-29 Eisai R & D Man Co Halichondrin analogs and methods of their use and preparation
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
CA2567984C (en) 2004-06-03 2014-05-20 Eisai Co., Ltd. Intermediates for the preparation of analogs of halichondrin b
US20060045846A1 (en) 2004-08-30 2006-03-02 Horstmann Thomas E Reagents and methods for labeling terminal olefins
EP1831697A4 (en) 2004-12-09 2011-01-26 Eisai R&D Man Co Ltd SCREENING OF TUBULIN ISOTYPE IN CANCER THERAPY USING ANALOGUES OF HALICHONDRIN B
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
EP2578576B9 (en) 2007-10-03 2016-09-14 Eisai R&D Management Co., Ltd. Intermediates for the synthesis of halichondrin B analogs
JP5134686B2 (ja) 2007-11-16 2013-01-30 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アナログ合成のための新規な中間体及び前記中間体に用いるための新規な脱スルホニル化反応
BRPI0911269A2 (pt) 2008-04-04 2015-09-29 Eisai R&D Man Co Ltd análogos de halicondrina b
SG182612A1 (en) 2010-01-26 2012-08-30 Eisai R&D Man Co Ltd Furo [3, 2 -b] pyrane derivatives useful in the synthesis of halichondrin b analogs
WO2012147900A1 (en) 2011-04-28 2012-11-01 Eisai R&D Management Co., Ltd. Microreactor process for halichondrin b analog synthesis
US9181152B2 (en) 2011-11-30 2015-11-10 Alphora Research Inc. Process for preparation of (3R)-2,4-di-leaving group-3-methylbut-1-ene
WO2013142999A1 (en) 2012-03-30 2013-10-03 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein
MX2015007185A (es) 2012-12-04 2017-09-05 Eisai R&D Man Co Ltd Uso de eribulina en el tratamiento de cancer de pecho.
AU2014286880B2 (en) 2013-07-03 2017-12-14 Sandoz Ag Synthetic process for preparation of macrocyclic C1-keto analogs of Halichondrin B and intermediates useful therein including intermediates containing -SO2-(p-TOLYL) groups
JP6625533B2 (ja) 2013-11-04 2019-12-25 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
RU2676486C1 (ru) * 2013-12-06 2018-12-29 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Способы, предназначенные для синтеза аналогов галихондрина b
EP3113775A4 (en) 2014-03-03 2017-08-23 Eisai R&D Management Co., Ltd. Use of eribulin and mtor inhibitors as combination therapy for the treatment of cancer
US10238630B2 (en) 2014-05-28 2019-03-26 Eisai R&D Management Co., Ltd. Use of eribulin and poly (ADP ribose) polymerase (PARP) inhibitors as combination therapy for the treatment of cancer
CN106413705A (zh) 2014-05-28 2017-02-15 卫材R&D管理有限公司 艾日布林在治疗癌症中的用途
SG11201706872SA (en) 2015-03-04 2017-09-28 Merck Sharp & Dohme Combination of a pd-1 antagonist and eribulin for treating cancer
RU2020141025A (ru) 2015-05-07 2020-12-28 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Реакции макроциклизации и промежуточные соединения и другие фрагменты, полезные в синтезе макролидов галихондринов
SG11201806133UA (en) 2016-02-12 2018-08-30 Eisai R&D Man Co Ltd Intermediates in the synthesis of eribulin and related methods of synthesis
SG11201811671XA (en) 2016-06-30 2019-01-30 Eisai R&D Man Co Ltd Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof

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