Design and synthesis of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. Part 3: In vitro evaluation of 1,3,4,5-Tetrahydro-benzo[c][1,6]- and [c][1,7]-naphthyridin-6-ones

Dana Ferraris, Rica Pargas Ficco, Thomas Pahutski, Susan Lautar, Shirley Huang, Jie Zhang, Vincent Kalish

Research output: Contribution to journalArticlepeer-review

Abstract

The 1,3,4,5-tetrahydro-benzo[c][1,6]- and [c][1,7]-napthyridin-6-ones are presented as a potent class of PARP-1 inhibitors. Derivatives of these partially saturated aza-5[H]-phenanthridin-6-ones were designed and synthesized with tertiary amines for salt formation, thus enhancing aqueous solubility, iv formulation and their potential use in acute ischemic injuries (i.e., myocardial ischemia and stroke). We found that partial saturation of the C-ring results in derivatives that are several times more potent than the aromatic C-ring derivatives. The general synthetic routes are presented herein as well as thorough in vitro potencies and SAR discussion for selected derivatives.

Original languageEnglish (US)
Pages (from-to)2513-2518
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number15
DOIs
StatePublished - Aug 4 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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