Quinazolinedione derivatives as PARP inhibitors

摘要

Disclosed is a compound of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein each X is independently N or CH and when X is CH then Y is N each Y is independently N or CH and when X is CH then Y is N L1 is a direct bond or a bivalent radical selected from -C1-6alkanediyl-; L2 is a direct bond or a bivalent radical selected from carbonyl, -C1-6alkanediyl-, -(Hydroxy) C1-6alkanediyl-, -C(O)-C1-6alkanediyl- or-C1-6alkanediyl-C(O)-; R1 is hydrogen or hydroxy; Z is hydrogen or a radical selected from (a-1) (a-2) (a-3) (a-4) (a-5) as shown in specification wherein each R2 is independently selected from hydrogen, halo or C1-6alkyl; with the proviso that the quinazolinedione moiety is attached to the rest of the molecule on the -NH-moiety in the 1-position in which case the hydrogen atom is replaced; and with the proviso that 1-[1-[(2S)-2-[(2R)-3,4-dihydro-2H-1-benzopyran-2-yl]-2-hydroxyethyl]-4-piperidinyl]-2,4 (1H, 3H)-quinazolinedione, 1-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4-(1H, 3H)quinazolinedione, and 1-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]-2,4-(1H, 3H)quinazolinedione are not included.