title: Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase.
abstract: The synthesis and biological evaluation of a series of N-alkyl glycine amide analogs as LTA(4)-h inhibitors and the importance of the introduction of a benzoic acid group to the potency and pharmacokinetic parameters of our analogs are described. The lead compound in the series, 4q, has excellent potency and oral bioavailability.
authors.affiliation: Department of Medicinal Chemistry, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.forename: John
authors.initials: J
authors.lastname: Bauman
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Davey
authors.forename: Seock-Kyu
authors.initials: SK
authors.lastname: Khim
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: Amy
authors.initials: A
authors.lastname: Liang
authors.forename: Dao
authors.initials: D
authors.lastname: Lentz
authors.forename: Karen
authors.initials: K
authors.lastname: May
authors.forename: Lisa
authors.initials: L
authors.lastname: Mendoza
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.forename: Victor
authors.initials: V
authors.lastname: Selchau
authors.forename: Sabine
authors.initials: S
authors.lastname: Schlyer
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: John
authors.initials: J
authors.lastname: Parkinson
authors.forename: William J
authors.initials: WJ
authors.lastname: Guilford
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019817:Benzoic Acid / Q000737:chemistry; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D004987:Ethers; D005998:Glycine / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical
chemical_list: D000577:Amides; D000588:Amines; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D004987:Ethers; D019817:Benzoic Acid; D004851:Epoxide Hydrolases; D005998:Glycine; C043134:leukotriene A4 hydrolase