Discovery and bioactivity of 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl) morpholine derivatives as novel PI3K inhibitors

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):339-42. doi: 10.1016/j.bmcl.2011.11.003.
Jia Wang  1 ,  Xiang Wang ,  Yanhong Chen ,  Simeng Chen ,  Guang Chen ,  Linjiang Tong ,  Linghua Meng ,  Yuyuan Xie ,  Jian Ding ,  Chunhao Yang
Affiliations
  • 1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China.
PMID: 22130133 DOI: 10.1016/j.bmcl.2011.11.003
Abstract

PI3K is a promising therapeutic target for Cancer. With PI-103 as the lead compound, we designed and synthesized 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl)morpholine derivatives. 9, 10a, 10d, 10e had the IC(50) against PI3Kα comparable with PI-103. All of the compounds showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several Cancer cell lines.