Eisai R&d Management Co., Ltd.

Otsuka Pharmaceutical Company, Limited

Epizyme, Inc.

Hyeong-wook Choi

Francis Gerard Fang

Dae-Shik Kim

Frank Fang

Charles E Chase

Jaemoon Lee

Steven Mathieu

Atsushi Endo

Ming-Hong Hao

Kuan-Chun Huang

Xingfeng Bao

Wanjun Zheng

Yimin Jiang

Jing Li

Bryan Matthew Lewis

Hong Du

Silvio A Campagna

Robert Yu

Daniel Custar

Xiaojie Zhu

Maarten Postema

Kevin Wayne Kuntz

Arani Chanda

Kristen Sanders

Mingde Shan

Robert T Yu

Provided herein are methods for the treatment of bladder cancer.

Methods for the treatment of bladder cancer

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.

Macrocyclization reactions and intermediates and other fragments useful in the synthesis of analogs of halichondrin B

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.

Prins reaction and compounds useful in the synthesis of halichondrin macrolides and analogs thereof

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

EP4 antagonists

Provided herein are compounds useful for the treatment of cancer.

Compounds for the treatment of cancer

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.

Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof

The present invention relates to methods and intermediates for synthesizing 2'-deoxy-2&#x2032;,2&#x2032;-difluorotetrahydrouridine compounds.

Synthetic route to 2'-deoxy-2&#x2032;,2&#x2032;-difluorotetrahydrouridines

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.

The invention provides methods for the synthesis of a halichondrin macrolides 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), catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic macrolide. The invention also provides compounds useful as intermediates in the synthesis of a halichondrin macrolides and methods for preparing the same.

Macrocyclization reactions and intermediates and other fragments useful in the synthesis of halichondrin macrolides

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.

Growing community of inventors

Andover, MA, United States of America

Hyeong-wook Choi