title: Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine.
abstract: With an aim to identify a dispiro-1,2,4-trioxolane with high oral activity and good physicochemical properties, 27 derivatives of an achiral piperidine trioxolane were synthesized; most were potent antimalarial peroxides with IC(50)s ranging from 0.20 to 7.0 ng/mL. The oral efficacies of two of these were superior to artesunate and comparable to artemether. The attractive chemical simplicity of these compounds is balanced only by an apparent metabolic susceptibility.
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Maniyan
authors.initials: M
authors.lastname: Padmanilayam
authors.forename: Bernard
authors.initials: B
authors.lastname: Scorneaux
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Dong
authors.forename: Jacques
authors.initials: J
authors.lastname: Chollet
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Susan A
authors.initials: SA
authors.lastname: Charman
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Creek
authors.forename: William N
authors.initials: WN
authors.lastname: Charman
authors.forename: Josefina Santo
authors.initials: JS
authors.lastname: Tomas
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Vennerstrom
mesh_terms: D000588:Amines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008862:Microsomes, Liver / Q000502:physiology; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014508:Urea / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000588:Amines; D000962:Antimalarials; D010880:Piperidines; D013449:Sulfonamides; D014508:Urea