| Literature DB >> 27793566 |
Huagang Lu1, John Rogowskyj1, Wenquan Yu1, Anu Venkatesh2, Noshena Khan1, Shigeki Nakagawa2, Nicolas Goossens2, Anna P Koh2, Takaaki Higashi2, Ganesh Gunasekaran3, Myron E Schwarz3, Spiros P Hiotis4, Xiaodong Xu1, William Kinney1, Yujin Hoshida2, Timothy Block1, Andrea Cuconati5, Yanming Du6.
Abstract
Based on our previous identification of a disubstituted aminothiazole termed HBF-0079 with promising selective toxicity for HCC-derived cell lines versus non-HCC liver lines, a series of tri-substituted aminothiazole derivatives were prepared and evaluated. This work resulted in the discovery of isopropyl 4-(pyrazin-2-yl)-2-(pyrimidin-2-ylamino)thiazole-5-carboxylate, 14, which displayed EC50 value of 0.11μM and more than 450times of selectivity, and its methyl carbonate prodrug 24 with improved solubility in organic solvents. Furthermore, 14, was shown to reduce the proliferation of several liver cancer cells derived directly from patients.Entities:
Keywords: Hepatocellular carcinoma (HCC); Prodrug; Substituted aminothiazole
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Year: 2016 PMID： 27793566 PMCID： PMC6317351 DOI： 10.1016/j.bmcl.2016.10.015
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.940