Sabat Mark, Vanrens John C, Clark Michael P, Brugel Todd A, Maier Jennifer, Bookland Roger G, Laufersweiler Matthew J, Laughlin Steven K, Golebiowski Adam, De Biswanath, Hsieh Lily C, Walter Richard L, Mekel Marlene J, Janusz Michael J
Procter and Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA.
Bioorg Med Chem Lett. 2006 Aug 15;16(16):4360-5. doi: 10.1016/j.bmcl.2006.05.050. Epub 2006 Jun 5.
A series of C-2, C-8, and N-9 trisubstituted purine based inhibitors of TNF-alpha production are described. The most potent analogs showed low nanomolar activity against LPS-induced TNF-alpha production in a THP-1 cell based assay. The SAR of the series was optimized with the aid of X-ray co-crystal structures of these inhibitors bound with mutated p38 (mp38).
描述了一系列基于C-2、C-8和N-9三取代嘌呤的肿瘤坏死因子-α（TNF-α）产生抑制剂。在基于THP-1细胞的试验中，最有效的类似物对脂多糖（LPS）诱导的TNF-α产生显示出低纳摩尔活性。借助这些抑制剂与突变型p38（mp38）结合的X射线共晶体结构，对该系列的构效关系进行了优化。
