公开(公告)号：US20210347779A1

公开(公告)日：2021-11-11

申请号：US17141557

申请日：2021-01-05

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Wanjun ZHENG ,  Xiaojie ZHU ,  Hong DU ,  Maarten POSTEMA ,  Yimin JIANG ,  Jing LI ,  Robert YU ,  Hyeong-Wook CHOI ,  Jaemoon LEE ,  Francis G. FANG ,  Daniel CUSTAR

IPC: C07D487/04 ,  C07D519/00 ,  A61P35/00

Abstract: We provide compounds given by Formula I, which is shown in FIG. 3, or pharmaceutically acceptable salts thereof, as well as formulations thereof and methods of use of those compounds and formulations for treatment of cancer.

公开(公告)号：US20190144463A1

公开(公告)日：2019-05-16

申请号：US16246999

申请日：2019-01-14

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Francis G. FANG ,  Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Charles E. CHASE ,  Jaemoon LEE

IPC: C07D493/22 ,  C07F7/18 ,  C07D493/14 ,  C07D407/14 ,  C07D307/28 ,  C07D407/06

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

公开(公告)号：US20210188867A1

公开(公告)日：2021-06-24

申请号：US17188819

申请日：2021-03-01

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Francis G. FANG ,  Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Charles E. CHASE ,  Jaemoon LEE

IPC: C07D493/22 ,  C07F7/18 ,  C07D407/14 ,  C07D307/28 ,  C07D407/06 ,  C07D493/14

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

公开(公告)号：US20160264594A1

公开(公告)日：2016-09-15

申请号：US15033970

申请日：2014-11-04

Applicant: Francis G. FANG ,  Eisai R&D Management Co., Ltd.

Inventor： Francis G. FANG ,  Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Charles E. CHASE ,  Jaemoon LEE

IPC: C07D493/22 ,  C07D307/28 ,  C07D493/14 ,  C07F7/18 ,  C07D407/06

CPC classification number: C07D493/22 ,  C07D307/28 ,  C07D407/06 ,  C07D407/14 ,  C07D493/14 ,  C07F7/1804

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Abstract translation: 本发明提供了通过大环化策略合成干燥蛋白或其药学上可接受的盐（例如甲磺酸艾美林）的方法。 本发明的大环化策略涉及使非大环中间体进行碳 - 碳键形成反应（例如，烯化反应（例如，Homer-Wadsworth-Emmons烯化），Dieckmann反应，催化闭环烯烃复分解， 或Nozaki-Hiyama-Kishi反应），得到大环中间体。 本发明还提供了用作合成干扰素或其药学上可接受的盐的中间体的化合物及其制备方法。

公开(公告)号：US20200223864A1

公开(公告)日：2020-07-16

申请号：US16833923

申请日：2020-03-30

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Francis G. FANG ,  Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Charles E. CHASE ,  Jaemoon LEE

IPC: C07D493/22 ,  C07F7/18 ,  C07D407/14 ,  C07D307/28 ,  C07D407/06 ,  C07D493/14

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

公开(公告)号：US20180002342A1

公开(公告)日：2018-01-04

申请号：US15707412

申请日：2017-09-18

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Francis G. FANG ,  Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Charles E. CHASE ,  Jaemoon LEE

IPC: C07D493/22 ,  C07D407/14 ,  C07D307/28 ,  C07D407/06 ,  C07F7/18 ,  C07D493/14

CPC classification number: C07D493/22 ,  C07D307/28 ,  C07D407/06 ,  C07D407/14 ,  C07D493/14 ,  C07F7/1804

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.