7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors

Bioorg Med Chem. 2014 Feb 1;22(3):1089-103. doi: 10.1016/j.bmc.2013.12.031. Epub 2013 Dec 22.


7-Azaindole-1-carboxamides were designed as a new class of PARP-1 inhibitors. The compounds displayed a variable pattern of target inhibition profile that, in part, paralleled the antiproliferative activity in cell lines characterized by homologous recombination defects. A selected compound (1l; ST7710AA1) showed significant in vitro target inhibition and capability to substantially bypass the multidrug resistance mediated by Pgp. In antitumor activity studies against the MX1 human breast carcinoma growth in nude mice, the compound exhibited an effect similar to that of Olaparib in terms of tumor volume inhibition when used at a lower dose than the reference compound. Treatment was well tolerated, as no deaths or significant weight losses were observed among the treated animals.

Keywords: 7-Azaindoles; Antitumor; Molecular modelling; PARP inhibitors; Synthesis.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • HeLa Cells / drug effects
  • Homologous Recombination
  • Humans
  • Indoles / chemistry
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • 7-azaindole dimer
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Enzyme Inhibitors
  • Indoles
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1