Du Xiaohui, Gustin Darin J, Chen Xiaoqi, Duquette Jason, McGee Lawrence R, Wang Zhulun, Ebsworth Karen, Henne Kirk, Lemon Bryan, Ma Ji, Miao Shichang, Sabalan Emmanuel, Sullivan Timothy J, Tonn George, Collins Tassie L, Medina Julio C
Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
Bioorg Med Chem Lett. 2009 Sep 1;19(17):5200-4. doi: 10.1016/j.bmcl.2009.07.021. Epub 2009 Jul 9.
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.
确定了一种提高具有稠合杂双环核心的CXCR3拮抗剂效力的通用方法。通过优化，发现了一系列咪唑并吡嗪衍生物，这些衍生物除了效力增加外，还具有改善的药代动力学性质。在小鼠肺部炎症模型中评估了先导化合物21的疗效。
