Neuropilins are the co-receptors of the VEGF receptors, implicated in angiogenesis and lymphangiogenesis. Due to their expression on endothelial, tumor and immune cells, and so to their role in angiogenesis, lymphangiogenesis and in the activation of the immune system, thay have become relevant oncology target. Thus, in this article, we report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1. The preparation of NRPa-308 proved challenging because of the orthogonality of the amide and sulphonamide bonds formation. Nevertheless, we succeeded a gram scale synthesis, according to an expeditious three steps route, without intermediate purification. This latter point is of utmost interest in reducing the ecologic impact and production costs in the perspective of further scale-up processes. This synthesis enables to obtain a pure and chemically stable compound.
NRPa-308 has shown biological effects in triple negative breast cancer (MDA-MB231) and is currently tested in the Clear Cell Renal cell carcinoma.
Brachet, E., Dumond, A., Liu, W. Q., Fabre, M., Selkti, M., Raynaud, F., Hermine, O., Benhida, R., Belmont, P., Garbay, C., Lepelletier, Y., Ronco, C., Pagès, G., Demange, L. (2019). Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent. Bioorganic & medicinal chemistry letters, 29(24), 126710.