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

Narendar Reddy Gade; Jatinder Kaur; Atul Bhardwaj; Edris Ebrahimi; Jennifer Dufour; Melinda Wuest; Frank Wuest

doi:10.1021/acsmedchemlett.3c00087

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. eCollection 2023 Jul 13.

Authors

Narendar Reddy Gade¹, Jatinder Kaur¹, Atul Bhardwaj¹, Edris Ebrahimi¹, Jennifer Dufour¹, Melinda Wuest¹, 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
PMCID: PMC10351058 (available on 2024-07-13)
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.