title: Imidazo-pyrazine derivatives as potent CXCR3 antagonists.
abstract: A general way of improving the potency of CXCR3 antagonists with fused hetero-bicyclic cores was identified. Optimization efforts led to the discovery of a series of imidazo-pyrazine derivatives with improved pharmacokinetic properties in addition to increased potency. The efficacy of the lead compound 21 is evaluated in a mouse lung inflammation model.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. xdu@amgen.com
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Du
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Gustin
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Chen
authors.forename: Jason
authors.initials: J
authors.lastname: Duquette
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: McGee
authors.forename: Zhulun
authors.initials: Z
authors.lastname: Wang
authors.forename: Karen
authors.initials: K
authors.lastname: Ebsworth
authors.forename: Kirk
authors.initials: K
authors.lastname: Henne
authors.forename: Bryan
authors.initials: B
authors.lastname: Lemon
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Shichang
authors.initials: S
authors.lastname: Miao
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sabalan
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sullivan
authors.forename: George
authors.initials: G
authors.lastname: Tonn
authors.forename: Tassie L
authors.initials: TL
authors.lastname: Collins
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D044482:Benzeneacetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003499:Cyclic S-Oxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008968:Molecular Conformation; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D044482:Benzeneacetamides; D003499:Cyclic S-Oxides; D007093:Imidazoles; D011719:Pyrazines; D054367:Receptors, CXCR3