RU2489437C2 - Промежуточные соединения и способы синтеза аналогов галихондрина в - Google Patents
Промежуточные соединения и способы синтеза аналогов галихондрина в Download PDFInfo
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- RU2489437C2 RU2489437C2 RU2010117520/04A RU2010117520A RU2489437C2 RU 2489437 C2 RU2489437 C2 RU 2489437C2 RU 2010117520/04 A RU2010117520/04 A RU 2010117520/04A RU 2010117520 A RU2010117520 A RU 2010117520A RU 2489437 C2 RU2489437 C2 RU 2489437C2
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- Prior art keywords
- compound
- alkyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract 80
- 238000000034 method Methods 0.000 title claims abstract 46
- 230000015572 biosynthetic process Effects 0.000 title abstract 3
- 238000003786 synthesis reaction Methods 0.000 title abstract 3
- FXNFULJVOQMBCW-VZBLNRDYSA-N halichondrin b Chemical class O([C@@H]1[C@@H](C)[C@@H]2O[C@@H]3C[C@@]4(O[C@H]5[C@@H](C)C[C@@]6(C[C@@H]([C@@H]7O[C@@H](C[C@@H]7O6)[C@@H](O)C[C@@H](O)CO)C)O[C@H]5C4)O[C@@H]3C[C@@H]2O[C@H]1C[C@@H]1C(=C)[C@H](C)C[C@@H](O1)CC[C@H]1C(=C)C[C@@H](O1)CC1)C(=O)C[C@H](O2)CC[C@H]3[C@H]2[C@H](O2)[C@@H]4O[C@@H]5C[C@@]21O[C@@H]5[C@@H]4O3 FXNFULJVOQMBCW-VZBLNRDYSA-N 0.000 title abstract 2
- 125000006239 protecting group Chemical group 0.000 claims abstract 52
- 239000000203 mixture Substances 0.000 claims abstract 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 19
- 125000005843 halogen group Chemical group 0.000 claims abstract 8
- 150000003839 salts Chemical class 0.000 claims abstract 6
- 238000002425 crystallisation Methods 0.000 claims abstract 4
- 125000004122 cyclic group Chemical group 0.000 claims 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 18
- -1 triethylsilyl Chemical group 0.000 claims 15
- 150000005676 cyclic carbonates Chemical class 0.000 claims 11
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 9
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 9
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 claims 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 5
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 5
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 5
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims 5
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 5
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 125000003118 aryl group Chemical group 0.000 claims 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 230000008025 crystallization Effects 0.000 claims 3
- PWAPCRSSMCLZHG-UHFFFAOYSA-N cyclopentylidene Chemical group [C]1CCCC1 PWAPCRSSMCLZHG-UHFFFAOYSA-N 0.000 claims 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- 230000029936 alkylation Effects 0.000 claims 2
- 238000005804 alkylation reaction Methods 0.000 claims 2
- 239000012296 anti-solvent Substances 0.000 claims 2
- 239000000010 aprotic solvent Substances 0.000 claims 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims 2
- 239000002798 polar solvent Substances 0.000 claims 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims 1
- FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 claims 1
- 150000001350 alkyl halides Chemical class 0.000 claims 1
- 239000006184 cosolvent Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 0 C[C@](CC(CC1)OC2(C*)C1OC(CCC(OC)=O)C2)C#N Chemical compound C[C@](CC(CC1)OC2(C*)C1OC(CCC(OC)=O)C2)C#N 0.000 description 3
- OTVBRNAYANIQFA-DYCFOQDWSA-N CCC12OC(C[C@@H](C)C#N)CCC1OC(CCCO)C2 Chemical compound CCC12OC(C[C@@H](C)C#N)CCC1OC(CCCO)C2 OTVBRNAYANIQFA-DYCFOQDWSA-N 0.000 description 1
- IKBOKNUXODLFIO-QMWYMAEDSA-N C[C@H](CC(CC1)OC(CO)(C2)C1OC2/C=C/C(OC)=O)C#N Chemical compound C[C@H](CC(CC1)OC(CO)(C2)C1OC2/C=C/C(OC)=O)C#N IKBOKNUXODLFIO-QMWYMAEDSA-N 0.000 description 1
- NLJHXBUSKQNGEM-UWJCENJNSA-N C[C@H](CC(CC1)OC2(CO)C1OC(CCC(OC)=O)C2)C#N Chemical compound C[C@H](CC(CC1)OC2(CO)C1OC(CCC(OC)=O)C2)C#N NLJHXBUSKQNGEM-UWJCENJNSA-N 0.000 description 1
- DHRWKMUNZUXHIB-DNEFCUBASA-N C[C@H](C[C@@H](CC1)OC(CI)(C2)C1OC2[C@@H]1OC2(CCCCC2)OC1)C#N Chemical compound C[C@H](C[C@@H](CC1)OC(CI)(C2)C1OC2[C@@H]1OC2(CCCCC2)OC1)C#N DHRWKMUNZUXHIB-DNEFCUBASA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—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
- 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
- C07D307/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- 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
- C07D307/28—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- 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
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Furan Compounds (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99762507P | 2007-10-03 | 2007-10-03 | |
| US60/997,625 | 2007-10-03 | ||
| PCT/US2008/078762 WO2009046308A1 (en) | 2007-10-03 | 2008-10-03 | Intermediates and methods for the synthesis of halichondrin b analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2010117520A RU2010117520A (ru) | 2011-11-10 |
| RU2489437C2 true RU2489437C2 (ru) | 2013-08-10 |
Family
ID=40019255
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2010117520/04A RU2489437C2 (ru) | 2007-10-03 | 2008-10-03 | Промежуточные соединения и способы синтеза аналогов галихондрина в |
Country Status (11)
| Country | Link |
|---|---|
| US (6) | US8093410B2 (OSRAM) |
| EP (2) | EP2578576B9 (OSRAM) |
| JP (1) | JP5735277B2 (OSRAM) |
| CN (3) | CN108948039B (OSRAM) |
| BR (1) | BRPI0817909B1 (OSRAM) |
| CA (1) | CA2701534C (OSRAM) |
| IL (1) | IL204791A (OSRAM) |
| MX (1) | MX2010003599A (OSRAM) |
| RU (1) | RU2489437C2 (OSRAM) |
| SG (1) | SG10201811715YA (OSRAM) |
| WO (1) | WO2009046308A1 (OSRAM) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2676486C1 (ru) * | 2013-12-06 | 2018-12-29 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Способы, предназначенные для синтеза аналогов галихондрина b |
| US10221189B2 (en) | 2013-11-04 | 2019-03-05 | Eisai R&D Management Co., Ltd. | Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin B |
| US10676481B2 (en) | 2016-02-12 | 2020-06-09 | Eisai R&D Management Co., Ltd. | Intermediates in the synthesis of eribulin and related methods of synthesis |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2682878B2 (ja) | 1989-11-27 | 1997-11-26 | 上村工業株式会社 | シールド付き電気めっき装置 |
| DK1087960T3 (da) | 1998-06-17 | 2011-06-14 | Eisai R&D Man Co Ltd | Makrocykliske analoger og fremgangsmåder til deres anvendelse og fremstilling |
| US7982060B2 (en) | 2004-06-03 | 2011-07-19 | Eisai R&D Management Co., Ltd. | Intermediates for the preparation of analogs of Halichondrin B |
| WO2009046308A1 (en) | 2007-10-03 | 2009-04-09 | Eisai R & D Management Co., Ltd. | Intermediates and methods for the synthesis of halichondrin b analogs |
| SG189739A1 (en) | 2008-04-04 | 2013-05-31 | Eisai R&D Man Co Ltd | Halichondrin b analogs |
| DE102009012660A1 (de) * | 2009-03-13 | 2010-09-16 | H.C. Starck Clevios Gmbh | Polymerbeschichtungen mit verbesserter Temperaturstabilität |
| MY160203A (en) | 2009-03-30 | 2017-02-28 | Eisai R&D Man Co Ltd | Liposome composition |
| EP2528914B1 (en) | 2010-01-26 | 2014-06-11 | Eisai R&D Management Co., Ltd. | Furo[3,2-b]pyrane derivatives useful in the synthesis of halichondrin b analogs |
| CN102225921B (zh) * | 2011-04-26 | 2013-04-24 | 中国人民解放军第二军医大学 | 一种环戊烷聚酮类化合物simplextone A及其用途 |
| WO2012147900A1 (en) | 2011-04-28 | 2012-11-01 | Eisai R&D Management Co., Ltd. | Microreactor process for halichondrin b analog synthesis |
| EP2928464A1 (en) | 2012-12-04 | 2015-10-14 | Eisai R&D Management Co., Ltd. | Use of eribulin in the treatment of breast cancer |
| KR102265952B1 (ko) | 2013-06-26 | 2021-06-16 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 암 치료 병용요법으로서 에리불린 및 렌바티닙의 용도 |
| SG11201609777SA (en) | 2014-05-28 | 2016-12-29 | Eisai R&D Man Co Ltd | Use of eribulin in the treatment of cancer |
| EP3160970A4 (en) | 2014-06-30 | 2017-12-27 | President and Fellows of Harvard College | Synthesis of halichondrin analogs and uses thereof |
| US10208058B2 (en) | 2014-09-09 | 2019-02-19 | Cipla Limited | Process for the preparation of macrocyclic ketone analogs of halichondrin B or pharmaceutically acceptable salts and intermediates thereof |
| CA2978226C (en) | 2015-03-04 | 2025-02-18 | Eisai R&D Management Co., Ltd. | COMBINATION OF A PD-1 ANTAGONIST AND A VEGFR/FGFR/RET TYROSINE KINASE INHIBITOR TO TREAT CANCER |
| EP3265122B1 (en) | 2015-03-04 | 2022-05-04 | Merck Sharp & Dohme Corp. | Combination of pembrolizumab and eribulin for treating triple-negative breast 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 |
| RU2739034C2 (ru) | 2015-05-07 | 2020-12-21 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Реакции макроциклизации и промежуточное соединение и другие фрагменты, полезные в синтезе макролидов галихондринов |
| SMT202100416T1 (it) | 2016-03-02 | 2021-09-14 | Eisai R&D Man Co Ltd | Coniugati anticorpo-farmaco a base di eribulina e metodi di uso |
| JP7015237B2 (ja) | 2016-04-28 | 2022-02-02 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍の成長を抑制する方法 |
| CN114805322B (zh) * | 2016-06-30 | 2025-05-30 | 卫材R&D管理有限公司 | 可用于合成软海绵素大环内酯类及其类似物的普林斯反应和中间体 |
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| US11643418B2 (en) | 2013-11-04 | 2023-05-09 | Eisai R&D Management Co., Ltd. | Macrocyclization reactions and intermediates and other fragments useful in the synthesis of analogs of halichondrin B |
| RU2676486C1 (ru) * | 2013-12-06 | 2018-12-29 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Способы, предназначенные для синтеза аналогов галихондрина b |
| US10676481B2 (en) | 2016-02-12 | 2020-06-09 | Eisai R&D Management Co., Ltd. | Intermediates in the synthesis of eribulin and related methods of synthesis |
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