Copper-Mediated Radiosynthesis of [18F]Rucaparib

Org Lett. 2021 Sep 17;23(18):7290-7294. doi: 10.1021/acs.orglett.1c02770. Epub 2021 Aug 30.

Abstract

The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the 18F-isotopologue of rucaparib by applying a copper-mediated nucleophilic 18F-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-18F-labeling and affords [18F]rucaparib with an activity yield of 11% ± 3% (n = 3) and a molar activity (Am) up to 30 GBq/μmol. Preliminary in vitro studies are presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / chemistry*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / chemistry*
  • BRCA2 Protein / genetics
  • Copper / chemistry*
  • Female
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Molecular Structure
  • Poly(ADP-ribose) Polymerase Inhibitors / chemical synthesis*
  • Poly(ADP-ribose) Polymerase Inhibitors / chemistry

Substances

  • BRCA1 Protein
  • BRCA2 Protein
  • Indoles
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Copper
  • rucaparib