1048364-22-2Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of thiazoles targeting flavivirus envelope proteins
Mayhoub, Abdelrahman S.,Khaliq, Mansoora,Kuhn, Richard J.,Cushman, Mark
scheme or table, p. 1704 - 1714 (2011/05/05)
A series of third-generation analogues of methyl 4-(dibromomethyl)-2-(4- chlorophenyl)thiazole-5-carboxylate (1), which had the most potent antiviral activity among the first- and second-generation compounds, have been synthesized and tested against yellow fever virus using a cell-based assay. The compounds were designed with the objectives of improving metabolic stability, therapeutic index, and antiviral potency. The biological effects of C4 and C5 substitution were examined. The methylthio ester and the dihydroxypropylamide analogues had the best antiviral potencies and improved therapeutic indices and metabolic stabilities relative to the parent compound 1.
Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins
Li, Ze,Khaliq, Mansoora,Zhou, Zhigang,Post, Carol Beth,Kuhn, Richard J.,Cushman, Mark
experimental part, p. 4660 - 4671 (2009/07/11)
Flavivirus envelope proteins (E proteins) have been shown to play a pivotal role in virus assembly, morphogenesis, and infection of host cells. Inhibition of flavivirus infection of a host cell by means of a small molecule envelope protein antagonist is an attractive strategy for the development of antiviral agents. Virtual screening of the NCI chemical database using the dengue virus envelope protein structure revealed several hypothetical hit compounds. Bioassay results identified a class of thiazole compounds with antiviral potency in cell-based assays. Modification of these lead compounds led to a series of analogues with improved antiviral activity and decreased cytotoxicity. The most active compounds 11 and 36 were effective in the low micromolar concentration range in a cellular assay system.
