title: Expeditious synthesis and biological evaluation of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines as potential antimalarials.
abstract: A small set of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines was prepared possessing a flexible tether between the exocyclic nitrogen bonded to C-6 of the 1,2-dihydro-1,3,5-triazine-4,6-diamine heterocycle and the distal aryl ring. Three zones were varied in this series of compounds, namely the nature of the substituent(s) on C-2; the nature of the substituent(s) on the distal aryl ring; as well as the nature and length of the flexible tether between the rings. The compound showing the best antimalarial activity (cycloguanil-resistant FCR-3 Plasmodium falciparum IC50=0.99 μM) was N6-(3-(4-chlorophenoxy)propyl)-2-(furan-2-yl)-1,2-dihydro-1,3,5-triazine-4,6-diamine hydrochloride.
authors.affiliation: Discovery Chemistry, CSIR Biosciences, Private Bag X2, Modderfontein 1645, Johannesburg, South Africa. david.gravestock@gmail.com
authors.forename: David
authors.initials: D
authors.lastname: Gravestock
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Rousseau
authors.forename: Anna C U
authors.initials: AC
authors.lastname: Lourens
authors.forename: Simon S
authors.initials: SS
authors.lastname: Moleele
authors.forename: Robyn L
authors.initials: RL
authors.lastname: van Zyl
authors.forename: Paul A
authors.initials: PA
authors.lastname: Steenkamp
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; C560934:N6-(3-(4-chlorophenoxy)propyl)-2-(furan-2-yl)-1,2-dihydro-1,3,5-triazine-4,6-diamine; D014227:Triazines