Mycophenolic acid analogs with a modified metabolic profile

Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively metabolized into an inactive C7-glucuronide and removed from circulation. To circumvent the metabolic liability imposed by the C7-hydroxyl group, we have designed a series of hybrid MPA analogs based on the pharmacophores present in MPA and new generations of inosine monophosphate dehydrogenase (IMPDH) inhibitors. The synthesis of MPA analogs has been accomplished by an allylic substitution of a common lactone. Biological evaluations of these analogs and a preliminary structure–activity relationship (SAR) are presented.

Aiming to circumvent the metabolic liability imposed by mycophenolic acid (MPA), a series of MPA analogs have been designed by combining the structural elements of MPA and known IMPDH inhibitors.Figure optionsDownload as PowerPoint slide