Vale, NunoMatos, JoanaGut, JiriNogueira, Fatimado Rosario, VirgilioRosenthal, Philip J.Moreira, RuiGomes, Paula2015-12-302015-12-302008BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - Vol. 18, n. 14 (2008), p. 4150-41530960-894Xhttp://hdl.handle.net/10451/21672The synthesis of imidazolidin-4-one derivatives of primaquine containing the five-membered ring at the C-terminus of a dipeptide backbone coupled to the parent drug is described. These peptidomimetic derivatives were active against a chloroquine-resistant Plasmodium falciparum strain and inhibited the development of the sporogonic cycle of Plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. The novel imidazolidin-4-ones are extremely stable, both in human plasma and in pH 7.4 buffer, as a result of N-1-acylation. Thus, 'internal' imidazolidin-4-ones derived from dipeptidyl 8-aminoquinolines represent a new entry in antimalarial structure-activity relationships. (c) 2008 Elsevier Ltd. All rights reserved.application/pdfengChemistry, MedicinalChemistry, Organicjournal articlehttp://dx.doi.org/10.1016/j.bmcl.2008.05.076