Novel Inhibitors Of Inosine Monophosphate Dehydrogenase (Impdh)

Treatment of mycophenolic alcohol 2 with methylenebis(phosphonic dichloride) afforded the desired bis(phosphonate) S and its disubstituted analogue 9. Both compounds were found to be potent inhibitors of IMPDH. Also, a simple monophosphate analogue 7 showed potent activity. Thus, metabolically stable phosphonate derivatives 13-16 were prepared and as expected were found to be potent inhibitors of IMPDH. These results indicate that phosphonate analogues of MPA may be of therapeutic interest.