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Abstract: A series of novel aza vinyl sulfones were designed, synthesized in good yields and evaluated as antiplasmodial agents. Tested compounds did not show activity against papain or the Plasmodium falciparum cysteine protease falcipain-2. However, a number of the new compounds effectively inhibited the in vitro development of P. falciparum. Compounds containing a squaramide group were the most active, with IC50 values between 0.95 and 4.5μM, suggesting that these are potential lead compounds for the development of new antimalarial agents. [Copyright &y& Elsevier]

Abstract: The first structure–activity relationship study of vinyl sulfones as caspase-3 inhibitors is reported. A series of 12 vinyl sulfones was synthesized and evaluated for two downstream caspases (caspases-3 and -7). Dipeptidyl derivatives were significantly superior to their counterparts containing only Asp at P1, as caspase-3 inhibitors. Fmoc-Val-Asp-trans-CH;SO2Me was the most potent inhibitor of caspase-3 in the series, with a IC50 of 29 μM and a second-order rate constant of inactivation, k inact/K i, of 1.5 M−1 s−1. Computational studies suggest that the second amino acid occupies position S3 of the enzyme. In addition, Fmoc-Val-Asp-trans-CH;SO2Ph was inactive for caspase-7 for the tested concentrations. [ABSTRACT FROM AUTHOR]

Abstract: The first examples of low temperature N-oxy-3-aza Cope rearrangements, leading to functionalised allenes are described, where the Z-configuration of the enaminic double bond in the rearranging system proves critical. [Copyright &y& Elsevier]