Synthesis, in Vitro Evaluation and Cocrystal Structure of 4‑Oxo-[1]benzopyrano[4,3‑<i>c</i>]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate Dehydrogenase (<i>Cp</i>IMPDH) Inhibitors

Cryptosporidium inosine 5′-monophosphate dehydrogenase (<i>Cp</i>IMPDH) 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-<i>c</i>]­pyrazole derivative was identified as a moderately potent (IC₅₀ = 1.5 μM) inhibitor of <i>Cp</i>IMPDH. We report a SAR study for this compound series resulting in <b>8k</b> (IC₅₀ = 20 ± 4 nM). In addition, an X-ray crystal structure of <i>Cp</i>IMPDH·IMP·<b>8k</b> is also presented