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.
Original language | English |
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Pages (from-to) | 1916-1921 |
Number of pages | 6 |
Journal | Journal of Enzyme Inhibition and Medicinal Chemistry |
Volume | 36 |
Issue number | 1 |
DOIs | |
State | Published - 2021 |
ID: 85382835