title: Synthesis and biological evaluation of new imidazo[1,2-a]pyridine derivatives designed as mefloquine analogues.
abstract: This paper describes the synthesis and the in vitro antimalarial profile of two new imidazo[1,2-a]pyridine derivatives 4HCl and 13HCl, structurally proposed as mefloquine (1) analogues, by exploring bioisosterism and molecular simplification tools. The synthetic route employed to access the title compounds used, as starting material, the previously described ethyl 2-methylimidazo[1,2-aJpyridine-3-carboxylate derivative (5). These novel heterocyclic derivatives 4HCl and 13HCl presented modest antimalarial activity against the W-2 and D-6 clones of Plasmodium falciparum as well as inhibitors of in vitro heme polymerization compared to mefloquine.
authors.affiliation: Laboratório de Avaliação e Sintese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, RJ, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Lima
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Avery
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Helio M
authors.initials: HM
authors.lastname: de Alves
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002999:Clone Cells; D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007536:Isomerism; D015767:Mefloquine / Q000031:analogs & derivatives*; D008968:Molecular Conformation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D007093:Imidazoles; D011725:Pyridines; C029899:imidazole; D015767:Mefloquine