公开(公告)号：US20230151022A1

公开(公告)日：2023-05-18

申请号：US18089971

申请日：2022-12-28

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

Inventor： Hyeong-Wook CHOI ,  Francis G. FANG

IPC: C07D493/22 ,  C07D307/28 ,  C07D493/04 ,  C07D407/06 ,  C07D407/14

CPC classification number: C07D493/22 ,  C07D307/28 ,  C07D493/04 ,  C07D407/06 ,  C07D407/14

Abstract: The invention provides methods utilizing Prins reaction in the preparation of compounds that may be useful as intermediates in the synthesis of halichondrin macrolides and analogs thereof. The invention also provides compounds that may be useful as intermediates in the synthesis of a halichondrin macrolides and methods for preparing the same.

公开(公告)号：US20220195437A1

公开(公告)日：2022-06-23

申请号：US17643807

申请日：2021-12-10

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

Inventor： Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Francis G. FANG ,  Yoshinori TAKAHASHI ,  Kenji KIKUTA ,  Hikaru YOSHIMURA ,  Wataru ITANO ,  Toshiki KUROKAWA ,  Ryo DAIRIKI ,  Zhi ZHOU ,  Mingde SHAN

IPC: C12N15/113 ,  A61K31/712 ,  A61P25/28

Abstract: Antisense oligonucleotides are provided. These antisense oligonucleotides are useful in the preparation of gapmers for inhibition of Tau mRNA transcription. Inhibition of Tau mRNA transcription may result in decrease of amounts of Tau protein in a subject, allowing treatment of diseases and disorders related to expression of Tau, including Alzheimer's disease and primary tauopathies.

公开(公告)号：US20150175620A1

公开(公告)日：2015-06-25

申请号：US14577417

申请日：2014-12-19

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

Inventor： Atsushi ENDO ,  Charles E. CHASE ,  Francis G. FANG

IPC: C07D493/04 ,  C07D307/38

CPC classification number: C07F7/1804 ,  C07D307/12 ,  C07D307/38 ,  C07D405/06 ,  C07D405/12 ,  C07D407/06 ,  C07D493/04 ,  Y02P20/55

Abstract: In general, the invention features compounds useful for the synthesis of analogs of halichondrin B, such as eribulin or pharmaceutically acceptable salts thereof, e.g., eribulin mesylate. Exemplary compounds are of formula (I), (II), or (III):

Abstract translation: 通常，本发明的特征在于可用于合成软骨素B的类似物的化合物，例如胡椒素或其药学上可接受的盐，例如甲磺酸埃布林。 示例性化合物具有式（I），（II）或（III）：

公开(公告)号：US20140221635A1

公开(公告)日：2014-08-07

申请号：US14250086

申请日：2014-04-10

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

Inventor： Francis G. FANG ,  Bryan M. LEWIS ,  Matthew SCHNADERBECK

IPC: C07D493/20 ,  C07D493/10 ,  C07H15/26 ,  C07D317/72

CPC classification number: C07F7/1804 ,  A61K31/341 ,  C07C33/423 ,  C07D307/12 ,  C07D307/28 ,  C07D307/33 ,  C07D317/72 ,  C07D407/06 ,  C07D407/14 ,  C07D493/04 ,  C07D493/08 ,  C07D493/10 ,  C07D493/18 ,  C07D493/20 ,  C07D493/22 ,  C07F7/188 ,  C07H15/26 ,  Y02P20/55

Abstract: Intermediates and methods of their use in the synthesis of anslogs of halichondrin B are provided.

Abstract translation: 提供了中间体及其在软骨素B的合成中的应用。

公开(公告)号：US20220112207A1

公开(公告)日：2022-04-14

申请号：US17421922

申请日：2020-01-09

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

Inventor： Francis G. FANG ,  Branko MITASEV ,  Jiong YANG

IPC: C07D491/147 ,  C07D403/06 ,  C07D487/04 ,  C07D405/14 ,  C07C311/18 ,  C07D307/33

Abstract: A method for the synthesis of diazabicyclo[6.2.0]decane compounds is provided. The synthesis proceeds by stereoselective synthesis of a chiral lactone followed by azetidine formation via a series of chemoselective reactions. Bicyclization results with the formation of diazobicyclo[6.2.0]decane related compounds.

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：US20180162885A1

公开(公告)日：2018-06-14

申请号：US15840109

申请日：2017-12-13

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

Inventor： Atsushi ENDO ,  Charles E. CHASE ,  Francis G. FANG

IPC: C07F7/18 ,  C07D307/38 ,  C07D407/06 ,  C07D493/04 ,  C07D405/12 ,  C07D307/12 ,  C07D405/06

CPC classification number: C07F7/1804 ,  C07D307/12 ,  C07D307/38 ,  C07D405/06 ,  C07D405/12 ,  C07D407/06 ,  C07D493/04 ,  Y02P20/55

Abstract: In general, the invention features compounds useful for the synthesis of analogs of halichondrin B, such as eribulin or pharmaceutically acceptable salts thereof, e.g., eribulin mesylate. Exemplary compounds are of formula (I), (II), or (III):

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：US20150225415A1

公开(公告)日：2015-08-13

申请号：US14624033

申请日：2015-02-17

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

Inventor： Charles E. CHASE ,  Atsushi ENDO ,  Francis G. FANG ,  Jing LI

IPC: C07D493/20 ,  C07D493/18 ,  C07D493/08 ,  C07D307/28 ,  C07D307/33

CPC classification number: C07D493/20 ,  C07D307/20 ,  C07D307/26 ,  C07D307/28 ,  C07D307/33 ,  C07D309/16 ,  C07D405/06 ,  C07D405/14 ,  C07D493/04 ,  C07D493/08 ,  C07D493/18 ,  C07D493/22 ,  Y02P20/55

Abstract: Methods of synthesizing intermediates useful for the synthesis of halichondrin B analogs are described.

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.