title: Synthesis of azole nucleoside 5'-monophosphate mimics (P1Ms) and their inhibitory properties of IMP dehydrogenases.
abstract: 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.
authors.affiliation: Biota, Inc., Carlsbad, California 92008, USA. g.wang@biota-inc.com
authors.forename: Guangyi
authors.initials: G
authors.lastname: Wang
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Sakthivel
authors.forename: Vasanthakumar
authors.initials: V
authors.lastname: Rajappan
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bruice
authors.forename: Kathleen
authors.initials: K
authors.lastname: Tucker
authors.forename: Patrick
authors.initials: P
authors.lastname: Fagan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Brooks
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hurd
authors.forename: Janet M
authors.initials: JM
authors.lastname: Leeds
authors.forename: P Dan
authors.initials: PD
authors.lastname: Cook
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D009711:Nucleotides; D007168:IMP Dehydrogenase