Structure-activity relationship studies of prostate-specific membrane antigen (PSMA) inhibitors derived from α-amino acid with (S)- or (R)-configuration at P1′ region

PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives

“…For example, Kim et al demonstrated the negative impacts on affinity towards PSMA when employing βand γ-amino acids compared to the α-amino acid counterparts [68]. Similar negative effects were observed by Kwon et al by inverting the configuration of the α-amino acid in the binding region of the moiety [69]. Other efforts related to the design of binding entities were based on sulfamides [70], carbamates [71,72], thioureas [64,73] and dimeric peptides [74,75].…”

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

“…It should be noted that the ( S )-configuration was chosen as comprehensive SAR studies have also demonstrated that the ( R )-configuration of the glutamate results in a severely reduced inhibitory activity. 30,32–34…”

“…It should be noted that the (S)-configuration was chosen as comprehensive SAR studies have also demonstrated that the (R)-configuration of the glutamate results in a severely reduced inhibitory activity. 30,[32][33][34] Initial attention focused on the synthesis of allyl glutamate 4, beginning with conversion of glutamate 6 to 2-nitrophenylsulfonyl (2-nosyl) N a -protected 8 in 72% yield using a selective mono 2-nitrobenzene-1-sulfonyl chloride protocol described by Wang et al (Scheme 3). 35 This strategy was implemented to Scheme 1 Formation of cyclized side products via condensation/ dehydration reported by Martin et al 21 Scheme 2 Retrosynthetic rationale to the design of cyclic PSMA inhibitor (1b).…”