Efficient synthesis of a galectin inhibitor clinical candidate (TD139) using a Payne rearrangement/azidation reaction cascade

Org Biomol Chem. 2020 May 27;18(20):3903-3907. doi: 10.1039/d0ob00910e.

Abstract

Selective galectin inhibitors are valuable research tools and could also be used as drug candidates. In that context, TD139, a thiodigalactoside galectin-3 inhibitor, is currently being evaluated clinically for the treatment of idiopathic pulmonary fibrosis. Herein, we describe a new strategy for the preparation of TD139. Starting from inexpensive levoglucosan, we used a rarely employed reaction cascade: Payne rearrangement/azidation process leading to 3-azido-galactopyranose. The latter intermediate was efficiently converted into TD139 in a few simple and practical steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / antagonists & inhibitors*
  • Blood Proteins / metabolism
  • Carbohydrate Conformation
  • Crystallography, X-Ray
  • Galectins / antagonists & inhibitors*
  • Galectins / metabolism
  • Humans
  • Models, Molecular
  • Thiogalactosides / chemical synthesis
  • Thiogalactosides / chemistry
  • Thiogalactosides / pharmacology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Blood Proteins
  • Galectins
  • LGALS3 protein, human
  • Thiogalactosides
  • Triazoles
  • GB-0139