Synthesis, in Vitro Evaluation and Cocrystal Structure of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate Dehydrogenase (CpIMPDH) Inhibitors
نویسندگان
چکیده
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.
منابع مشابه
Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity
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عنوان ژورنال:
دوره 57 شماره
صفحات -
تاریخ انتشار 2014