Synthesis of isoquinolinone-based tricycles as novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors

  • Bioorg Med Chem Lett. 2014 Jun 15;24(12):2669-73. doi: 10.1016/j.bmcl.2014.04.061.
Jianyang Chen  1 ,  Haixia Peng  1 ,  Jinxue He  2 ,  Xiajuan Huan  2 ,  Zehong Miao  3 ,  Chunhao Yang  4
Affiliations
  • 1. Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
  • 2. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
  • 3. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. Electronic address: [email protected].
  • 4. Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. Electronic address: [email protected].
PMID: 24815508 DOI: 10.1016/j.bmcl.2014.04.061
Abstract

The isoquinolinone-based tricyclic compounds were designed and synthesized. Preliminary biological study of these compounds provided potent compounds 17a, 33b, 33c, 33d, and 33g with low nanomolar IC50s against PARP-1 enzyme.

Keywords
Antitumor; Isoquinolinone-based tricycles; PARP-1 inhibitors.