Quinazolinedione derivatives as parp inhibitors
AssigneeJanssen Pharmaceutica NV
InventorsLudo Edmond Josephine Kennis, Josephus Carolus Mertens, Jacobus Alphonsus Josephus Van Dun, Maria Victorina Francisca Somers, Walter Boudewijn Leopold Wouters
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Abstract
The present invention provides compounds of formula (I), their use as PARP inhibitors as well as pharmaceutical compositions comprising said compounds of formula (I) wherein R1, L1, L2, X, Y and Z have defined meanings.
Claims20
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
- and when X is
- then Y is
- each Y is independently
- except when X is
- then Y is
- 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
- 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, 1-[3-[4-(4-fluorobenzoyl)-1-piperidinyl]propyl]-2,4-(1H, 3H)-quinazolinedione, 3-[2-[4-(4-chlorobenzoyl)-1-piperidinyl]ethyl]-2,4-(1H, 3H)-quinazolinedione and 3-[2-[4-[(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]ethyl]-2,4-(1H, 3H)-quinazolinedione are not included.
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A method for the treatment of a PARP mediated disorder using a therapeutically effective amount of a compound of formula (I)
- 3-[2-[4-[(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]ethyl]-2,4-(1H, 3H)-quinazolinedione
- the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof
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A combination of a compound with a chemotherapeutic agent wherein said compound 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
- and when X is
- then Y is
- each Y is independently
- except when X is
- then Y is
- 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
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Dependencies are inferred from the claim text.