Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Evaluation of Tricyclic Derivatives Containing a Non-Aromatic Amide as Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors

  • Park, Chun-Ho (Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co.) ;
  • Chun, Kwang-Woo (Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co.) ;
  • Choi, Jong-Hee (Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co.) ;
  • Ji, Wan-Keun (Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co.) ;
  • Kim, Hyun-Young (Department of Neurology, Hanyang University College of Medicine) ;
  • Kim, Seung-Hyun (Department of Neurology, Hanyang University College of Medicine) ;
  • Han, Gyoon-Hee (Department of Biotechnology, Yonsei University) ;
  • Kim, Myung-Hwa (Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co.)
  • Received : 2011.02.24
  • Accepted : 2011.03.31
  • Published : 2011.05.20
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Abstract

A series of potent tricyclic derivatives with a non-aromatic amide as potent PARP-1 inhibitors were successfully synthesized and their PARP-1 inhibitory activity was evaluated. Among the derivatives, 2-(1-propylpiperidin-4-yloxy)-7,8,9,10-tetrahydrophenanthridin-6(5H)-one 23c displayed potent activity in a PARP-1 enzymatic assay and cell-based assay ($IC_{50}$ = 0.142 ${\mu}M$, $ED_{50}$ = 0.90 ${\mu}M$) with good water solubility. Further, molecular modeling studies confirmed the obtained biological results.

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References

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