title: Discovery of novel and potent aryl diamines as leukotriene A4 hydrolase inhibitors.
abstract: The synthesis and biological evaluation of a series of aryl diamines as inhibitors of LTA(4)-h inhibitors are described. The optimization which led to the identification of the optimal para-substitution on the diphenyl ether moiety and diamine spacer is discussed. The resulting compounds such as 3l have excellent enzyme and cellular potency as well as desirable pharmacokinetic properties.
authors.affiliation: Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA.
authors.forename: Seock-Kyu
authors.initials: SK
authors.lastname: Khim
authors.forename: John
authors.initials: J
authors.lastname: Bauman
authors.forename: Jarred
authors.initials: J
authors.lastname: Evans
authors.forename: Beverly
authors.initials: B
authors.lastname: Freeman
authors.forename: Beverly
authors.initials: B
authors.lastname: King
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirkland
authors.forename: Monica
authors.initials: M
authors.lastname: Kochanny
authors.forename: Dao
authors.initials: D
authors.lastname: Lentz
authors.forename: Amy
authors.initials: A
authors.lastname: Liang
authors.forename: Lisa
authors.initials: L
authors.lastname: Mendoza
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.forename: Jih-Lie
authors.initials: JL
authors.lastname: Tseng
authors.forename: Robert G
authors.initials: RG
authors.lastname: Wei
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Limei
authors.initials: L
authors.lastname: Yu
authors.forename: John
authors.initials: J
authors.lastname: Parkinson
authors.forename: William J
authors.initials: WJ
authors.lastname: Guilford
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry; D004285:Dogs; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D003959:Diamines; D004791:Enzyme Inhibitors; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase