Synthesis and initial in vitro evaluation of PSMA-targeting ligands with a modified aromatic moiety at the lysine ε-nitrogen atom

• Published in: Bioorganic & medicinal chemistry letters Vol. 71; pp. 128840 - 128846
• Main Authors: Zyk, Nikolai Y., Ber, Anton P., Nimenko, Ekaterina A., Shafikov, Radik R., Evteev, Sergei A., Petrov, Stanislav A., Uspenskaya, Anastasia A., Dashkova, Natalia S., Ivanenkov, Yan A., Skvortsov, Dmitry A., Beloglazkina, Elena K., Majouga, Alexander G., Machulkin, Aleksei E.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2022; Elsevier
• Subjects: Chemistry; Chemistry, Medicinal; Chemistry, Organic; Drug delivery; Life Sciences & Biomedicine; Ligands; Pharmacology & Pharmacy; Physical Sciences; Prostate cancer; Prostate-specific membrane antigen; Science & Technology; Sulfo-Cy5; DUPA; PyBOP; DIPEA; Drug delivery; DCL; TFA; DCM; Prostate-specific membrane antigen; 2-PMPA; HOBt; Ligands; HBTU; GCPII; DMF; Prostate cancer; NAAG; Sulfo-Cy5; 2-MPPA; TIPS; DESIGN; GLUTAMATE CARBOXYPEPTIDASE-II; INHIBITORS; MEMBRANE ANTIGEN PSMA; PRECLINICAL EVALUATION
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2022.128840

[Display omitted] We report an improved series of ligands targeting prostate specific membrane antigen (PSMA). The new compounds were designed by the introduction of changes in the structure of the aromatic fragment at ε-nitrogen atom of lysine that resulted in improved biological parameters. Some of them demonstrated high selectivity and nanomolar IC50 values. We synthesized and tested two conjugates with a fluorescent label Sulfo-Cy5 as an example of the use of the obtained PSMA inhibitors as a basis for the creation of diagnostic preparations.