Discovery of protein–protein binding disruptors using multi-component condensations small molecules

A series of small molecule compounds interfering with the binding process of VEGF and NRP1 has been identified and further optimized. Full synthetic details as well as SAR are reported which demonstrate that expeditious MCC-based syntheses may lead to valuable molecules addressing challenging targets such as protein–protein interactions. Preliminary functional assay data confirm that these compounds may be further developed toward drug candidates.

Graphical abstractThe synthesis of the compound 53 (IC50 ELISA = 2 μM) and analogues is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide