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

Autor:	Jihan Khan, Deviprasad R. Gollapalli, Joon Hyung Cho, Andrzej Joachimiak, Lizbeth Hedstrom, Chalada Suebsuwong, Pascal Vo, Zhuming Sun, Magdalena Makowska-Grzyska, Minjia Zhang, Youngchang Kim, Gregory D. Cuny
Rok vydání:	2014
Předmět:	Models Molecular Brief Article Guanine Stereochemistry Dehydrogenase Pyrazole In Vitro Techniques Crystallography X-Ray 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship IMP Dehydrogenase IMP dehydrogenase Coumarins Drug Discovery medicine Structure–activity relationship Inosine-5′-monophosphate dehydrogenase Enzyme Inhibitors Inosine 030304 developmental biology Cryptosporidium parvum 0303 health sciences biology Molecular Structure 010405 organic chemistry biology.organism_classification 3. Good health 0104 chemical sciences chemistry Biochemistry biology.protein Molecular Medicine Pyrazoles Acetanilides medicine.drug
Zdroj:	Journal of Medicinal Chemistry
ISSN:	1520-4804
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87b3cf9e26ae89053f15f2e5f266a659 https://pubmed.ncbi.nlm.nih.gov/25474504 Zobrazit plný text záznamu