On the way to selective PARP-2 inhibitors. Design, synthesis, and prelimionary evaluation of a series of isoquinolinone derivatives

Pellicciari R., Camaioni E., Costantino G., Formentini L., Sabbatini P., Venturoni F., ...Daha Fazla

CHEMMEDCHEM, cilt.3, sa.6, ss.914-923, 2008 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 3 Sayı: 6
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1002/cmdc.200800010
  • Dergi Adı: CHEMMEDCHEM
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.914-923
  • Anahtar Kelimeler: isoquinolinones, medicinal chemistry, molecular docking, PARP-2 inhibitors, poly(ADP-ribosyl)ation, POLY(ADP-RIBOSE) POLYMERASE, CEREBRAL-ISCHEMIA, POTENT, SYNTHETASE, DISCOVERY, MOLECULE, DOCKING, MODEL
  • Gazi Üniversitesi Adresli: Evet

Özet

PARP-1 and PARP-2 are members of the family of poly(ADP-ribose)polymeroses, which are involved in the maintenance of genomic integrity under conditions of genotoxic stimuli. The different roles of the two isoforms under pathophysiological conditions have not yet been fully clarified, and this is partially due to the lack of selective inhibitors. We report herein the synthesis and preliminary pharmacological evaluation of a large series of isoquinolinone derivatives as PARP-1/PARP-2 inhibitors. Among them, we identified the 5-benzoyloxyisoquinolin-1(2H)-one derivative as the most selective PARP-2 inhibitor reported so for, with a PARP-2/PARP-1 selectivity index greater than 60.