Synthesis and development of seven-membered constrained cyclic urea based PSMA inhibitors via RCM

Abstract

Prostate-specific membrane antigen (PSMA) biomarkers have been recognized as a viable tool for diagnosing prostate cancer (PCa). Herein, we focus on the development of cyclic PSMA inhibitors adopting a urea-based scaffold. This details the use of intramolecular ring-closing metathesis (RCM) on a N,N-diallyl urea substrate to directly afford 7-membered cyclic urea derivatives. The synthesis of 7-membered cyclic ureas has confirmed that our constructs weakly recognise PSMA, the key enzyme in PCa, in addition to offering a direct RCM synthetic method to afford 7-memebred cyclic ureas.