2014
DOI: 10.1016/j.ejmech.2014.01.036
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Synthesis of febrifugine derivatives and development of an effective and safe tetrahydroquinazoline-type antimalarial

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Cited by 46 publications
(29 citation statements)
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“…The drugs HF, FF, 6F-FF, and Th-FF killed malaria parasites in the very first cycle of erythrocytic development, suggesting that the likely target for these inhibitors was cytoplasmic PfPRS and not apicoplastic PfPRS (Hoen et al, 2013). For each of the four tested inhibitors ( Figure 1A), dose-dependent inhibition followed sigmoidal curves with 50% effective concentration (EC 50 ) in the subnanomolar ranges of 1-190 nM ( Figure 1B), consistent with earlier reports (Derbyshire et al, 2012;Geary et al, 1983;Kikuchi et al, 2006Kikuchi et al, , 2014. The EC 50 values of HF were increased to 5 and 20 nM, respectively, in the presence of 53 and 203 L-Pro (RPMI media supplemented with higher L-Pro concentration) in the culture media, in line with a competitive inhibition mode of binding in context of the PRS natural substrate L-proline ( Figure 1B).…”
Section: Evaluation Of Prs-drug Binding and Inhibitionsupporting
confidence: 84%
“…The drugs HF, FF, 6F-FF, and Th-FF killed malaria parasites in the very first cycle of erythrocytic development, suggesting that the likely target for these inhibitors was cytoplasmic PfPRS and not apicoplastic PfPRS (Hoen et al, 2013). For each of the four tested inhibitors ( Figure 1A), dose-dependent inhibition followed sigmoidal curves with 50% effective concentration (EC 50 ) in the subnanomolar ranges of 1-190 nM ( Figure 1B), consistent with earlier reports (Derbyshire et al, 2012;Geary et al, 1983;Kikuchi et al, 2006Kikuchi et al, , 2014. The EC 50 values of HF were increased to 5 and 20 nM, respectively, in the presence of 53 and 203 L-Pro (RPMI media supplemented with higher L-Pro concentration) in the culture media, in line with a competitive inhibition mode of binding in context of the PRS natural substrate L-proline ( Figure 1B).…”
Section: Evaluation Of Prs-drug Binding and Inhibitionsupporting
confidence: 84%
“…Our investigation started with the reaction of N,Oacetal 5 a [19,20a] with phenylacetylene 6 a. First, wellknown catalysts SnCl 4 [17a,c] and Bi(OTf) 3 [18] were examined, and the results showed that catalytic amount of Bi(OTf) 3 could give the desired product 7 a in 9% yield, along with excellent diastereoselectivity (dr > 99:1) ( [11][12][13]. However, conducting the reaction at À 78°C to À 45°C led to lower yield of 42%, albeit still with high diastereoselectivity (dr > 99:1) ( Table 1, entry 14).…”
Section: Resultsmentioning
confidence: 99%
“…During the past 30 years, asymmetric synthesis of (+)-Febrifugine (1) or (+)-Halofuginone (3) has attracted wide attention and a number of powerful approaches have been reported. [12] Currently, almost all synthetic approaches started from chiral 3-hydroxy-2-substituted piperidine scaffold. During the past decade, we have made significant efforts to pursue the chiral building block 5-hydroxy-6-substituted piperidine lactam [13] and scalable synthesis of (+)-Halofuginone (3).…”
Section: Introductionmentioning
confidence: 99%
“…[11] Raltitrexed is ak nown anticancer treatment medication with possible ability to replace fluoropyrimidine drugs in treatments of colorectal cancer (CRC). [12] All these carry quinazoline framework.…”
Section: Introductionmentioning
confidence: 99%