Borzilleri Robert M, Cai Zhen-Wei, Ellis Christopher, Fargnoli Joseph, Fura Aberra, Gerhardt Tracy, Goyal Bindu, Hunt John T, Mortillo Steven, Qian Ligang, Tokarski John, Vyas Viral, Wautlet Barri, Zheng Xioping, Bhide Rajeev S
Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Bioorg Med Chem Lett. 2005 Mar 1;15(5):1429-33. doi: 10.1016/j.bmcl.2004.12.079.
A versatile synthesis of the suitably functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus is described. SAR at the C-5 and C-6 positions of the 4-(3-hydroxy-4-methylphenylamino)pyrrolo[2,1-f][1,2,4]triazine template led to compounds with good in vitro potency against VEGFR-2 kinase. Glucuronidation of the phenol group is mitigated by incorporation of a basic amino group on the C-6 side chain of the pyrrolotriazine nucleus.
本文描述了一种对功能适当化的吡咯并[2,1-f][1,2,4]三嗪核进行的通用合成方法。在4-(3-羟基-4-甲基苯基氨基)吡咯并[2,1-f][1,2,4]三嗪模板的C-5和C-6位进行的构效关系研究得到了对VEGFR-2激酶具有良好体外活性的化合物。通过在吡咯并三嗪核的C-6侧链上引入碱性氨基，可减轻酚羟基的葡萄糖醛酸化。
