公开(公告)号：US20240060068A1

公开(公告)日：2024-02-22

申请号：US18256428

申请日：2021-12-10

Applicant: Francis G. FANG ,  Dai-Shik KIM ,  Hyeong Wook CHOI ,  Yoshinori TAKAHASHI ,  Kenji KIKUTA ,  Hikaru KAWASHIMA ,  Toshiki KUROKAWA ,  Tamaki HOSHIKAWA ,  Mingde SHAN ,  John WANG ,  Eisai R&D Management Co., Ltd.

Inventor： Francis G. Fang ,  Dae-Shik Kim ,  Hyeong Wook Choi ,  Yoshinori Takahashi ,  Kenji Kikuta ,  Hikaru Kawashima ,  Wataru Itano ,  Toshiki Kurokawa ,  Tamaki Hoshikawa ,  Mingde SHAN ,  John Wang

IPC: C12N15/113 ,  C07H21/04

CPC classification number: C12N15/113 ,  C07H21/04 ,  C12N2310/341 ,  C12N2310/3233 ,  C12N2310/315

Abstract: Gapmers or pharmaceutically acceptable salt of the gapmers and methods of making the gapmers are provided. The gapmers include a gap region that contains deoxyribonucleosides linked to each other by phosphorothioate bonds, a 5′ wing region positioned at the 5′ end of the gap region that contains morpholino monomers linked to each other by phosphorodiamidate bonds, and a 3′ wing region positioned at the 3′ end of the gap region that contains morpholino monomers linked to each other by phosphorodiamidate bonds. Antisense oligonucleotides are also provided. These antisense oligonucleotides are useful in the preparation of gapmers for inhibition of Tau mRNA transcription.

公开(公告)号：US11136335B2

公开(公告)日：2021-10-05

申请号：US16313196

申请日：2017-06-30

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

Inventor： Charles E. Chase ,  Hyeong-Wook Choi ,  Atsushi Endo ,  Francis G. Fang ,  Dae-Shik Kim

IPC: C07D493/22

Abstract: The invention provides methods for the synthesis of a halichondrin macrolides or analogs thereof through a cyclization reaction strategy. The strategy of the present invention involves subjecting an intermediate to Prins reaction conditions to afford a macrolide. The invention also provides compounds useful as intermediates in the synthesis of a halichondrin macrolides or analogs thereof and methods for preparing the same.

公开(公告)号：US10793581B2

公开(公告)日：2020-10-06

申请号：US16521691

申请日：2019-07-25

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

Inventor： Francis G. Fang ,  Hyeong-wook Choi ,  Silvio Campagna ,  Steven Mathieu

IPC: C07D493/22 ,  C07B57/00 ,  C07D313/00 ,  C07D493/08 ,  C07D493/18

Abstract: The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries.

公开(公告)号：US10676481B2

公开(公告)日：2020-06-09

申请号：US16076028

申请日：2017-02-10

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

Inventor： Phil S. Baran ,  Charles E. Chase ,  Francis G. Fang

IPC: C07D493/00 ,  C07D493/22

Abstract: The invention relates to methods and intermediates useful in the synthesis of eribulin.

公开(公告)号：USRE47797E1

公开(公告)日：2020-01-07

申请号：US15944480

申请日：2018-04-03

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

Inventor： Farid Benayoud ,  Trevor Lee Calkins ,  Charles E. Chase ,  William Christ ,  Bryan M. Lewis ,  Matthew Schnaderbeck ,  Marc Pesant ,  Brian Austad ,  Silvio Campagna ,  Yongbo Hu ,  Gordon Wilkie ,  Xiaojie Zhu ,  Francis G. Fang

IPC: C07D307/28 ,  C07F7/18 ,  C07C33/42 ,  C07D407/06 ,  C07D407/14 ,  C07D493/04 ,  C07D493/08 ,  C07D493/18 ,  C07D493/22 ,  C07D493/20 ,  C07D317/72 ,  C07H15/26 ,  A61K31/341 ,  C07D307/12 ,  C07D493/10 ,  C07D307/33

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

公开(公告)号：US10221189B2

公开(公告)日：2019-03-05

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

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：USRE46965E1

公开(公告)日：2018-07-24

申请号：US13924892

申请日：2013-06-24

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

Inventor： Brian Austad ,  Charles E. Chase ,  Francis G. Fang ,  Trevor Calkins ,  Bryan M. Lewis

IPC: C07D307/12 ,  C07F7/18 ,  C07D407/06 ,  C07D407/14 ,  C07D493/04 ,  C07D493/08 ,  C07D493/18 ,  C07D493/22 ,  C07D493/20 ,  C07D317/72 ,  C07H15/26 ,  C07C33/42 ,  A61K31/341 ,  C07D493/10 ,  C07D307/28 ,  C07D307/33

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: The present invention provides macrocyclic compounds, synthesis of the same and intermediates thereto. Such compounds, and compositions thereof, are useful for treating or preventing proliferative disorders Formula (F-4).

公开(公告)号：US09227942B2

公开(公告)日：2016-01-05

申请号：US14396261

申请日：2013-04-25

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

Inventor： Kazuhiro Yoshizawa ,  Masayuki Omori ,  Yuzo Watanabe ,  Mitsuo Nagai ,  Masabumi Takahashi ,  Francis G. Fang

IPC: C07D241/24

CPC classification number: C07D241/24

Abstract: 5-(Difluoromethyl)pyrazine-2-carboxylic acid, which is a raw material for the construction of 5-(difluoromethyl)pyrazine-2-carboxamide, which is a common partial structural motif of the compound having an Aβ production inhibitory action or a BACE1 inhibitory action, can be industrially advantageously produced by decarboxylating 5-[carboxy(difluoro)methyl]pyrazine-2-carboxylic acid, which is obtainable from 5-chloropyrazine-2-carboxylate.

Abstract translation: 5-（二氟甲基）吡嗪-2-甲酸，其是用于构建具有A＆bgr的化合物的常见部分结构基序的5-（二氟甲基）吡嗪-2-甲酰胺的原料。 产生抑制作用或BACE1抑制作用，可在工业上有利地由5-氯吡嗪-2-羧酸酯得到5- [羧基（二氟）甲基]吡嗪-2-羧酸脱羧产生。

公开(公告)号：US20150087836A1

公开(公告)日：2015-03-26

申请号：US14396261

申请日：2013-04-25

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

Inventor： Kazuhiro Yoshizawa ,  Masayuki Omori ,  Yuzo Watanabe ,  Mitsuo Nagai ,  Masabumi Takahashi ,  Francis G. Fang

IPC: C07D241/24

CPC classification number: C07D241/24

Abstract: 5-(Difluoromethyl)pyrazine-2-carboxilic acid, which is a raw material for the construction of 5-(difluoromethyl)pyrazine-2-carboxamide, which is a common partial structural motif of the compound having an A production inhibitory action or a BACE1 inhibitory action, can be industrially advantageously produced by decarboxylating 5-[carboxy(difluoro)methyl]pyrazine-2-carboxylic acid, which is obtainable from 5-chloropyrazine-2-carboxylate.

Abstract translation: 5-（二氟甲基）吡嗪-2-甲酸，其是用于构建5-（二氟甲基）吡嗪-2-甲酰胺的原料，其是具有A产生抑制作用的化合物的常见部分结构基序或 BACE1抑制作用可以在工业上有利地由5-氯吡嗪-2-羧酸酯可得5- [羧基（二氟）甲基]吡嗪-2-羧酸脱羧制得。

公开(公告)号：US08962857B2

公开(公告)日：2015-02-24

申请号：US14269659

申请日：2014-05-05

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

Inventor： Francis G. Fang ,  James E. Foy ,  Lynn Hawkins ,  Charles Lemelin ,  Andre LesCarbeau ,  Xiang Niu ,  Kuo-Ming Wu

IPC: C07D263/02

CPC classification number: C07D263/14 ,  C07C217/28 ,  C07C271/16 ,  C07F9/091 ,  C07F9/1411 ,  C07F9/2408

Abstract: The present invention provides methods for preparing TLR-4 receptor agonist E6020: and stereoisomers thereof, which compounds are useful as an immunological adjuvants when co-administered with antigens such as vaccines for bacterial and viral diseases. Also provided are synthetic intermediates.

Abstract translation: 本发明提供了制备TLR-4受体激动剂E6020及其立体异构体的方法，当与抗原如用于细菌和病毒疾病的疫苗共同施用时，该化合物可用作免疫佐剂。 还提供了合成中间体。