Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50=5.29μM), coupled with a lack of cytotoxicity towards mammalian cells (TC50 >100μM).
Keywords: Michael acceptors; Microwave irradiation; Peptidomimetics; Pharmacokinetic parameters; Trypanosoma.
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