1H-Imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors: Separation of desired cellular activity from undesired tissue accumulation through optimization of basic nitrogen pka

Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pka of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pka 6–8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen.

Based on the theoretical understanding of the in vivo lysosomotropism, by manipulating the pka of the cathepsin S inhibitors, a set of compounds with pka 6–8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen.Figure optionsDownload as PowerPoint slide