Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide (MAD) have beenprepared as potential inhibitors of IMP dehydrogenase. A coupling of the mycophenolic (hydroxymethyl)phosphonate 6 with the phosphitylated adenosine analogue 11 followed by oxidation and deprotection affordedthe phosphophosphonate 8. A similar coupling between adenosine (hydroxymethyl)phosphonate 10 andphosphitylated mycophenolic alcohol 5 gave the corresponding phosphophosphonate 13. Both 8 and 13 (Ki= 20−87 nM) were found to be the most potent cofactor type inhibitors of IMP dehydrogenase.
