Synthesis and biological evaluation of 2,3-diaryl isoquinolinone derivatives as anti-breast cancer agents targeting ERα and VEGFR-2

  • Bioorg Med Chem Lett. 2014 May 1;24(9):2129-33. doi: 10.1016/j.bmcl.2014.03.042.
Zhichao Tang  1 ,  Shaoxiong Niu  1 ,  Fei Liu  1 ,  Kejing Lao  1 ,  Jingshan Miao  2 ,  Jinzi Ji  2 ,  Xiang Wang  2 ,  Ming Yan  2 ,  Luyong Zhang  2 ,  Qidong You  1 ,  Hong Xiao  3 ,  Hua Xiang  4
Affiliations
  • 1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 2. New Drug Screening Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 3. Nanjing Brain Hospital Affiliated to Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, PR China. Electronic address: [email protected].
  • 4. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: [email protected].
PMID: 24721727 DOI: 10.1016/j.bmcl.2014.03.042
Abstract

The Estrogen receptor α is recognized as important pharmaceutical target for breast Cancer therapy, and vascular endothelial growth factor receptors (VEGFRs) play important roles in tumor angiogenesis including breast Cancer. A series of 2,3-diaryl isoquinolinone derivatives were designed and synthesized targeting both Estrogen receptor α (ERα) and VEGFR-2. Bioactivity evaluation showed that compounds 7c, 7d and 7f exhibited significant anti-proliferative and anti-angiogenesis activities via ERα and VEGFR-2 dependent mechanisms.

Keywords
2,3-Diaryl isoquinolinone derivatives; Anti-breast cancer; ERα; Synthesis; VEGFR-2.