Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
J Med Chem. 2012 Jun 14;55(11):5337-49. doi: 10.1021/jm3002982. Epub 2012 May 18.
Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.
原肌球蛋白相关激酶 A（TrkA）被认为是癌症和疼痛治疗开发的有前途的靶点。在这项研究中，我们通过基于结构的设计策略设计并合成了一系列新型的基于 7-氮吲哚的 Trk 激酶抑制剂。通过改变 7-氮吲哚骨架 3 位和 5 位的官能团，我们研究了构效关系（SAR）图谱，并鉴定了一系列有效的 Trk 抑制剂。代表性衍生物在细胞增殖和细胞凋亡测定中表现出良好的活性。此外，这些抑制剂表现出显著的抗血管生成活性。
