Document Report Card

ID: ALA3351328

Journal: J Med Chem

Title: Synthesis, in vitro evaluation and cocrystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase (CpIMPDH) inhibitors.

Authors: Sun Z, Khan J, Makowska-Grzyska M, Zhang M, Cho JH, Suebsuwong C, Vo P, Gollapalli DR, Kim Y, Joachimiak A, Hedstrom L, Cuny GD.

Abstract: Cryptosporidium inosine 5'-monophosphate dehydrogenase (CpIMPDH) has emerged as a therapeutic target for treating Cryptosporidium parasites because it catalyzes a critical step in guanine nucleotide biosynthesis. A 4-oxo-[1]benzopyrano[4,3-c]pyrazole derivative was identified as a moderately potent (IC50 = 1.5 μM) inhibitor of CpIMPDH. We report a SAR study for this compound series resulting in 8k (IC50 = 20 ± 4 nM). In addition, an X-ray crystal structure of CpIMPDH·IMP·8k is also presented.

CiteXplore: 25474504

DOI: 10.1021/jm501527z