Almirall Research Center, Almirall Laboratories, Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain.
Bioorg Med Chem Lett. 2011 Nov 1;21(21):6253-7. doi: 10.1016/j.bmcl.2011.09.006. Epub 2011 Sep 10.
Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38α inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation.
晶体学结构信息被用于设计和合成一系列生物等排体衍生物，以替代先导系列 p38α 抑制剂中酰胺部分，该部分在人肝制剂中普遍不稳定。三唑衍生物 13 在大鼠中具有中等的生物利用度，并在炎症急性模型中表现出有效的体内活性。
