2024-03-28T11:12:24Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1785732021-12-27T16:13:18Zcom_10261_64com_10261_1col_10261_317
2019-03-26T12:30:04Z
urn:hdl:10261/178573
Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei
Pham, ThanhTruc
Walden, Madeline
Butler, Christopher
Díaz-González, Rosario
Pérez-Moreno, Guiomar
Ceballos-Pérez, Gloria
Gómez-Pérez, Veronica
García-Hernández, Raquel
Zecca, Henry
Krakoff, Emma
Kopec, Brian
Ichire, Ogar
Mackenzie, Caden
Pitot, Marika
Ruiz-Pérez, Luis Miguel
Gamarro, Francisco
González-Pacanowska, D.
Navarro, M.
Dounay, Amy B.
Ministerio de Economía, Industria y Competitividad (España)
Ministerio de Economía, Industria y Competitividad (España)
Ministerio de Economía, Industria y Competitividad (España)
Instituto de Salud Carlos III
Trypanosomiasis
HAT
Trypanosoma brucei
Quinazolinone
Hit-to-lead
In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.
2019-03-26T12:30:04Z
2019-03-26T12:30:04Z
2017-08-15
artículo
Bioorganic and Medicinal Chemistry Letters
0960-894X
http://hdl.handle.net/10261/178573
10.1016/j.bmcl.2017.07.032
1464-3405
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100010198
28729055
eng
https://www.ncbi.nlm.nih.gov/pubmed/28729055
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-79957-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68042-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-71444-P
closedAccess
Elsevier