Inhibitors of inosinic acid dehydrogenase. 2-Substituted inosinic acids.

A series of 2-substituted inosine monophosphate (IMP) and inosine derivatives were synthesized and tested for inhibitory activity against IMP dehydrogenase from Escherichia coli. All of the IMP analogues that possessed electron-withdrawing substituents on the phenyl ring of a benzylthio group placed at the 2-position of IMP showed strong inhibition, which was competitive with IMP. No evidence of hydrophobic interactions of the 2-substituent with the enzyme was observed.