Sun Zhuming, Khan Jihan, Makowska-Grzyska Magdalena, Zhang Minjia, Cho Joon Hyung, Suebsuwong Chalada, Vo Pascal, Gollapalli Deviprasad R, Kim Youngchang, Joachimiak Andrzej, Hedstrom Lizbeth, Cuny Gregory D
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
J Med Chem. 2014 Dec 26;57(24):10544-50. doi: 10.1021/jm501527z. Epub 2014 Dec 4.
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.
隐孢子虫肌苷5'-单磷酸脱氢酶（CpIMPDH）已成为治疗隐孢子虫寄生虫的一个治疗靶点，因为它催化鸟嘌呤核苷酸生物合成中的关键步骤。一种4-氧代-[1]苯并吡喃并[4,3-c]吡唑衍生物被鉴定为CpIMPDH的中等强度抑制剂（IC50 = 1.5 μM）。我们报告了对该化合物系列的构效关系研究，结果得到了8k（IC50 = 20 ± 4 nM）。此外，还给出了CpIMPDH·IMP·8k的X射线晶体结构。
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