Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA.
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6519-23. doi: 10.1016/j.bmcl.2009.10.049. Epub 2009 Oct 26.
As part of our research effort to discover B-Raf kinase inhibitors, we prepared a series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3-(trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge-binding hydrogen bond. With basic amine residues appended to C-3 aryl residues, cellular activity and solubility were enhanced over previously described compounds of this class.
作为我们发现 B-Raf 激酶抑制剂的研究工作的一部分，我们合成了一系列 C-3 取代的 N-(3-(吡唑并[1,5-a]嘧啶-7-基)苯基)-3-(三氟甲基)苯甲酰胺。X 射线晶体学研究表明，其中一种效力更强的抑制剂（10n）与 B-Raf 激酶结合，而不形成铰链结合氢键。在 C-3 芳基残基上附加碱性胺基后，与该类别的先前描述的化合物相比，细胞活性和溶解度得到了提高。
