Rapamycin analogs with reduced systemic exposure

The synthesis and biological activities of rapamycin (I) analogs modified at the C-40 position are reported. Emphasis placed on compounds that potentially have an improved safety profile on account of their shorter in vivo half-life when compared with rapamycin.

The synthesis and biological activities of highly efficacious rapamycin analogs 3 and 6 in various autoimmune disease models are reported. A shorter plasma half-life of 3 and 6, compared to rapamycin, was measured in rats, and a reduced t1/2 of 3 versus rapamycin was verified in patients.Figure optionsDownload as PowerPoint slide