DOI

An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC50 = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.

Язык оригиналаанглийский
Страницы (с-по)1916-1921
Число страниц6
ЖурналJournal of Enzyme Inhibition and Medicinal Chemistry
Том36
Номер выпуска1
DOI
СостояниеОпубликовано - 2021

    Предметные области Scopus

  • Поиск новых лекарств
  • Фармакология

ID: 85382835