Design, Synthesis, and Biological Evaluation of 2‑Hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 Antagonist and Its Comparison to Available Small Molecular PD-L1 Inhibitors

In search of a potent small molecular PD-L1 inhibitor,
we designed
and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile
moiety. Ligand’s performance was tested in vitro and compared
side-by-side with a known PD-L1 antagonist with a proven bioactivity
BMS1166. Subsequently, we modified both compounds to allow 18F labeling that could be used for PET imaging. Radiolabeling, which
is used in drug development and diagnosis, was applied to investigate
the properties of those ligands and test them against tissue sections
with diverse expression levels of PD-L1. We confirmed biological activity
toward hPD-L1 for this inhibitor, comparable with BMS1166, while holding
enhanced pharmacological properties.