N-Alkyl Carbamoylimidazoles as Versatile Synthons for the Synthesis of Urea-Based PSMA Inhibitors

  • ACS Med Chem Lett. 2023 Jun 9;14(7):943-948. doi: 10.1021/acsmedchemlett.3c00087.
Narendar Reddy Gade  1 ,  Jatinder Kaur  1 ,  Atul Bhardwaj  1 ,  Edris Ebrahimi  1 ,  Jennifer Dufour  1 ,  Melinda Wuest  1 ,  Frank Wuest  1  2  3
Affiliations
  • 1. Department of Oncology, University of Alberta, Edmonton, Alberta T6G 1Z2, Canada.
  • 2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2H1, Canada.
  • 3. Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
PMID: 37465305 DOI: 10.1021/acsmedchemlett.3c00087
Abstract

We describe N-alkyl carbamoylimidazoles as readily available and highly versatile synthons for synthesizing urea-based prostate-specific membrane antigen (PSMA) inhibitors. Urea formation proceeded in high yields (>80%) at room temperature under aqueous conditions. All novel compounds were tested for their PSMA inhibitory potency in a cell-based radiometric binding assay. Compound 17 was identified as a novel high-affinity PSMA Inhibitor (IC50 = 0.013 μM) suitable for developing an 18F-labeled radioligand for PET imaging of PSMA in prostate Cancer.

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