Imidazo-pyrazine derivatives as potent CXCR3 antagonists.
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.
Du
Xiaohui
X
Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. xdu@amgen.com
Gustin
Darin J
DJ
Chen
Xiaoqi
X
Duquette
Jason
J
McGee
Lawrence R
LR
Wang
Zhulun
Z
Ebsworth
Karen
K
Henne
Kirk
K
Lemon
Bryan
B
Ma
Ji
J
Miao
Shichang
S
Sabalan
Emmanuel
E
Sullivan
Timothy J
TJ
Tonn
George
G
Collins
Tassie L
TL
Medina
Julio C
JC
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
D000893:Anti-Inflammatory Agents; D044482:Benzeneacetamides; D003499:Cyclic S-Oxides; D007093:Imidazoles; D011719:Pyrazines; D054367:Receptors, CXCR3