Medicinal Chemistry, Sanofi-Aventis, 13 Quai Jules Guesde, 94300 Vitry-sur-Seine, France.
Chem Biol Drug Des. 2010 Aug;76(2):100-6. doi: 10.1111/j.1747-0285.2010.00991.x. Epub 2010 Jun 9.
From an azaindole lead, identified in high throughput screen, a series of potent bis-azaindole inhibitors of IGF1-R have been synthesized using rational drug design and SAR based on a in silico binding mode hypothesis. Although the resulting compounds produced the expected improved potency, the model was not validated by the co-crystallization experiments with IGF1-R.
从高通量筛选中确定的氮茚先导化合物出发，通过合理药物设计和基于体内结合模式假说的 SAR 研究，合成了一系列有效的双氮茚 IGF1-R 抑制剂。尽管所得化合物产生了预期的改善的活性，但该模型未通过与 IGF1-R 的共结晶实验进行验证。
