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Synthesis, in Vitro Evaluation and Cocrystal Structure of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate Dehydrogenase (CpIMPDH) Inhibitors
[Image: see text] 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...
| Autores principales: | , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2014
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281095/ https://www.ncbi.nlm.nih.gov/pubmed/25474504 http://dx.doi.org/10.1021/jm501527z |
| _version_ | 1782350937043501056 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Sun, Zhuming |
| collection | PubMed |
| description | [Image: see text] 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 (IC(50) = 1.5 μM) inhibitor of CpIMPDH. We report a SAR study for this compound series resulting in 8k (IC(50) = 20 ± 4 nM). In addition, an X-ray crystal structure of CpIMPDH·IMP·8k is also presented. |
| format | Online Article Text |
| id | pubmed-4281095 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2014 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-42810952015-12-04 Synthesis, in Vitro Evaluation and Cocrystal Structure of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate Dehydrogenase (CpIMPDH) Inhibitors 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. J Med Chem [Image: see text] 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 (IC(50) = 1.5 μM) inhibitor of CpIMPDH. We report a SAR study for this compound series resulting in 8k (IC(50) = 20 ± 4 nM). In addition, an X-ray crystal structure of CpIMPDH·IMP·8k is also presented. American Chemical Society 2014-12-04 2014-12-26 /pmc/articles/PMC4281095/ /pubmed/25474504 http://dx.doi.org/10.1021/jm501527z Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
| spellingShingle | 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. Synthesis, in Vitro Evaluation and Cocrystal Structure of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate Dehydrogenase (CpIMPDH) Inhibitors |
| 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 |
| title_full | Synthesis, in Vitro Evaluation
and Cocrystal Structure
of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate
Dehydrogenase (CpIMPDH) Inhibitors |
| title_fullStr | Synthesis, in Vitro Evaluation
and Cocrystal Structure
of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate
Dehydrogenase (CpIMPDH) Inhibitors |
| title_full_unstemmed | Synthesis, in Vitro Evaluation
and Cocrystal Structure
of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate
Dehydrogenase (CpIMPDH) Inhibitors |
| title_short | Synthesis, in Vitro Evaluation
and Cocrystal Structure
of 4-Oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum Inosine 5′-Monophosphate
Dehydrogenase (CpIMPDH) Inhibitors |
| title_sort | synthesis, in vitro evaluation
and cocrystal structure
of 4-oxo-[1]benzopyrano[4,3-c]pyrazole cryptosporidium parvum inosine 5′-monophosphate
dehydrogenase (cpimpdh) inhibitors |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281095/ https://www.ncbi.nlm.nih.gov/pubmed/25474504 http://dx.doi.org/10.1021/jm501527z |
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