Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, United States.
Bioorg Med Chem Lett. 2012 May 1;22(9):3311-6. doi: 10.1016/j.bmcl.2012.03.007. Epub 2012 Mar 10.
We describe an isostere-driven approach to improve upon a previously-described series of capped dipeptide antagonists of CC Chemokine Receptor 2 (CCR2). Modification of the substitution around the isostere was combined with additional changes in a distal aromatic substituent to provide single-digit nanomolar antagonists of CCR2. These studies led to the identification of 18, a compound that was suitable for studies in murine models of CCR2 activity.
我们描述了一种基于等排体的方法，用于改进之前描述的一系列 CC 趋化因子受体 2 (CCR2) 的 capped 二肽拮抗剂。在等排体周围的取代基进行修饰的同时，在远端芳基取代基上进行额外的改变，提供了对 CCR2 的单位数纳米摩尔拮抗剂。这些研究导致了 18 的鉴定，这是一种适合于 CCR2 活性的小鼠模型研究的化合物。
