Synthesis of azole nucleoside 5'-monophosphate mimics (P1Ms) and their inhibitory properties of IMP dehydrogenases.

IMPDH inhibitors have potential antimicrobial, anticancer and immunomodulatory effects. Nucleoside inhibitors of IMPDH exert their inhibitory effects via nucleoside 5′‐MPs. Conversion of nucleoside analogs to NMPs by cellular nucleoside kinases is not assured, and usually is inefficient. In order to bypass cellular phosphorylation, a series of azole nucleoside 5′‐MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C. albicans IMP dehydrogenises. P1Ms 8, 16, 25, 28 and 29 demonstrated substantial IMPDH inhibition with Ki values in low micromolar range. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.