title: Discovery of a potent, orally bioavailable pyrimidine VLA-4 antagonist effective in a sheep asthma model.
abstract: A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model.
authors.affiliation: Elan Pharmaceuticals, Inc., S. San Francisco, CA 94080, USA. semko@sbcglobal.net
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Semko
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.forename: Darren B
authors.initials: DB
authors.lastname: Dressen
authors.forename: Mark L
authors.initials: ML
authors.lastname: Dreyer
authors.forename: Whitney
authors.initials: W
authors.lastname: Dunn
authors.forename: Francine S
authors.initials: FS
authors.lastname: Farouz
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Freedman
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Holsztynska
authors.forename: Michael
authors.initials: M
authors.lastname: Jefferies
authors.forename: Andrei W
authors.initials: AW
authors.lastname: Konradi
authors.forename: Anna
authors.initials: A
authors.lastname: Liao
authors.forename: Judevin
authors.initials: J
authors.lastname: Lugar
authors.forename: Linda
authors.initials: L
authors.lastname: Mutter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pleiss
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Quinn
authors.forename: Thomas
authors.initials: T
authors.lastname: Thompson
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Thorsett
authors.forename: Christopher
authors.initials: C
authors.lastname: Vandevert
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Xu
authors.forename: Ted A
authors.initials: TA
authors.lastname: Yednock
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001682:Biological Availability; D004195:Disease Models, Animal; D055808:Drug Discovery; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012756:Sheep
chemical_list: D039041:Integrin alpha4beta1; D011743:Pyrimidines