Trans-Fluorine Effect in Cyclopropane: Diastereoselective Synthesis of Fluorocyclopropyl Cabozantinib Analogs

Janis Veliks (Coresponding Author), Melita Videja, Artis Kinens, Raitis Bobrovs, Martins Priede, Janis Kuka

Research output: Contribution to journalArticlepeer-review

Abstract

Investigation of the trans-fluorine effect on the hydrolysis rate of diethyl 2-fluorocyclopropane-1,1-dicarboxylate provides synthetic access to both diastereomers of the fluorocyclopropyl analog of cabozantinib, a c-Met and VEGFR-2 inhibitor used as a first-line treatment for thyroid cancer and as a second-line treatment for renal cell carcinoma. Despite some known potent examples, there are only a few drug molecules that contain fluorocyclopropane moieties. Herein, we present a case study in which the monofluoro analog of a known cyclopropane-containing drug molecule displays an improved in vitro profile compared to the parent nonfluorinated structure. The fluorocyclopropane moiety may offer valuable fine-tuning options for lead optimization in drug discovery.

Original languageEnglish
Pages (from-to)2146-2150
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume11
Issue number11
DOIs
Publication statusPublished - 12 Nov 2020

Keywords

  • anticancer
  • c-Met kinase inhibitors
  • cabozantinib
  • fluorocyclopropane
  • VEGFR-2 kinase inhibitors

Field of Science

  • 3.1 Basic medicine
  • 1.4 Chemical sciences

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

Fingerprint Dive into the research topics of 'Trans-Fluorine Effect in Cyclopropane: Diastereoselective Synthesis of Fluorocyclopropyl Cabozantinib Analogs'. Together they form a unique fingerprint.

Cite this