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
Hauptverfasser: 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
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container_end_page 44
container_issue 1
container_start_page 40
container_title ACS medicinal chemistry letters
container_volume 5
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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1948-5875
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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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