Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5‑Aminopyrazole-4-carboxamide Scaffold
5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known “bumped kinase inhibitor” to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum. Compounds with low nanomolar in...
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Veröffentlicht in: | ACS medicinal chemistry letters 2014-01, Vol.5 (1), p.40-44 |
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creator | Zhang, Zhongsheng Ojo, Kayode K Vidadala, RamaSubbaRao Huang, Wenlin Geiger, Jennifer A Scheele, Suzanne Choi, Ryan Reid, Molly C Keyloun, Katelyn R Rivas, Kasey Kallur Siddaramaiah, Latha Comess, Kenneth M Robinson, Kenneth P Merta, Philip J Kifle, Lemma Hol, Wim G. J Parsons, Marilyn Merritt, Ethan A Maly, Dustin J Verlinde, Christophe L. M. J Van Voorhis, Wesley C Fan, Erkang |
description | 5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known “bumped kinase inhibitor” to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum. Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be nontoxic to mammalian cells. |
doi_str_mv | 10.1021/ml400315s |
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The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be nontoxic to mammalian cells.</description><identifier>ISSN: 1948-5875</identifier><identifier>EISSN: 1948-5875</identifier><identifier>DOI: 10.1021/ml400315s</identifier><identifier>PMID: 24494061</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Letter</subject><ispartof>ACS medicinal chemistry letters, 2014-01, Vol.5 (1), p.40-44</ispartof><rights>Copyright © 2013 American Chemical Society</rights><rights>Copyright © 2013 American Chemical Society 2013 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a405t-2f34aa6693ab07e3e146f3ec8b388946702b2a41294abf58ae0b9a3f00b36f773</citedby><cites>FETCH-LOGICAL-a405t-2f34aa6693ab07e3e146f3ec8b388946702b2a41294abf58ae0b9a3f00b36f773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ml400315s$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ml400315s$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,2752,27053,27901,27902,53766,53768,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24494061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zhongsheng</creatorcontrib><creatorcontrib>Ojo, Kayode K</creatorcontrib><creatorcontrib>Vidadala, RamaSubbaRao</creatorcontrib><creatorcontrib>Huang, Wenlin</creatorcontrib><creatorcontrib>Geiger, Jennifer A</creatorcontrib><creatorcontrib>Scheele, Suzanne</creatorcontrib><creatorcontrib>Choi, Ryan</creatorcontrib><creatorcontrib>Reid, Molly C</creatorcontrib><creatorcontrib>Keyloun, Katelyn R</creatorcontrib><creatorcontrib>Rivas, Kasey</creatorcontrib><creatorcontrib>Kallur Siddaramaiah, Latha</creatorcontrib><creatorcontrib>Comess, Kenneth M</creatorcontrib><creatorcontrib>Robinson, Kenneth P</creatorcontrib><creatorcontrib>Merta, Philip J</creatorcontrib><creatorcontrib>Kifle, Lemma</creatorcontrib><creatorcontrib>Hol, Wim G. 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source | ACS Publications; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
subjects | Letter |
title | Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5‑Aminopyrazole-4-carboxamide Scaffold |
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