title: SAR of 2-amino and 2,4-diamino pyrimidines with in vivo efficacy against Trypanosoma brucei.
abstract: A series of 2,4-diaminopyrimidines was investigated and compounds were found to have in vivo efficacy against Trypanosoma brucei in an acute mouse model. However, in vitro permeability data suggested the 2,4-diaminopyrimidenes would have poor permeability through the blood brain barrier. Consequently a series of 4-desamino analogs were synthesized and found to have improved in vitro permeability.
authors.affiliation: SCYNEXIS Inc., PO Box 12878, Research Triangle Park, NC 27709-2878, USA. joe.perales@scynexis.com
authors.forename: Joe B
authors.initials: JB
authors.lastname: Perales
authors.forename: Jennifer
authors.initials: J
authors.lastname: Freeman
authors.forename: Cyrus J
authors.initials: CJ
authors.lastname: Bacchi
authors.forename: Tana
authors.initials: T
authors.lastname: Bowling
authors.forename: Robert
authors.initials: R
authors.lastname: Don
authors.forename: Eric
authors.initials: E
authors.lastname: Gaukel
authors.forename: Luke
authors.initials: L
authors.lastname: Mercer
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Moore
authors.forename: Bakela
authors.initials: B
authors.lastname: Nare
authors.forename: Tien M
authors.initials: TM
authors.lastname: Nguyen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Noe
authors.forename: Ryan
authors.initials: R
authors.lastname: Randolph
authors.forename: Cindy
authors.initials: C
authors.lastname: Rewerts
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wring
authors.forename: Nigel
authors.initials: N
authors.lastname: Yarlett
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jacobs
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D001812:Blood-Brain Barrier; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D010539:Permeability; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D000588:Amines; D011743:Pyrimidines; D014344:Trypanocidal Agents