Mehlmann John F, Crawley Matthew L, Lundquist Joseph T, Unwalla Ray J, Harnish Douglas C, Evans Mark J, Kim Callain Y, Wrobel Jay E, Mahaney Paige E
Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
Bioorg Med Chem Lett. 2009 Sep 15;19(18):5289-92. doi: 10.1016/j.bmcl.2009.07.148. Epub 2009 Aug 3.
Pyrrole[2,3-d]azepines have been identified as potent agonists of the farnesoid X receptor (FXR). Based on the planar X-ray crystal structure of WAY-362450 1 in the ligand binding domain and molecular modeling studies, non-planar reduced compounds were designed which led to agonists that exhibit high aqueous solubility and retain moderate in vitro potency.
吡咯并[2,3-d]氮杂卓已被确定为法尼醇X受体（FXR）的强效激动剂。基于配体结合域中WAY-362450 1的平面X射线晶体结构以及分子模拟研究，设计了非平面还原化合物，这些化合物产生了具有高水溶性且体外效力适中的激动剂。
