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US 7,803,795 B2Granted
Phthalazine derivatives as parp inhibitors
AssigneeJanssen Pharmaceutica NV
InventorsLaurence Anne Mevellec, Ludo 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, R2 L1, L2, X, Y, Q and Z have defined meanings.
Claims8
A compound of formula (I),
- the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein
- n is 0, 1, 2 or 3;
- Q is —C(═O)—;
- each X is independently —N< or —CH<;
- and when X is —CH< then Y is —N<, or —NH— and when X is —N< then Y is —CH═ or —CH2-;
- L1 is a direct bond or a bivalent radical selected from —C1-6alkanediyl-NH—, —NH— or —NH—C1-6alkanediyl-NH—;
- L2 is a direct bond or a bivalent radical selected from —C1-6alkanediyl-, —C2-6alkenediyl-, carbonyl or —C1-6alkanediyl-substituted with one substituent selected from hydroxy or aryl;
- R1 is hydrogen, nitro, halo or amino;
- R2 is hydrogen, C1-6alkyl or arylC1-6alkyl;
- the central
- moiety may also be bridged with an ethylene bridge;
- Z is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, aryloxy, amino, cyano, arylC1-6alkylamino or benzthiazolyl(C1-6alkyl)amino or
- a ring system selected from
- wherein R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy or trihalomethyl;
- aryl is phenyl, or phenyl substituted with one or two substituents each independently selected from halo, C1-6alkyl or C1-6alkyloxy;
- with the proviso that when Q is C(═O)— and X is —N< and Y is —CH< or —CH2 and L1 is a direct bond and L2 is a direct bond, or the bivalent radical —C1-6alkanediyl- or —C1-6alkanediyl-substituted with hydroxy and R1 is hydrogen and R2 is hydrogen or C1-6alkyl then Z is other than hydrogen, hydroxy or C1-6alkyl.
13 more elements
A compound selected from the group consisting of:
A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound of formula (I)
- the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein
- n is 0, 1, 2 or 3;
- Q is —C(═O)—;
- each X is independently —N< or —CH<;
- and when X is —CH< then Y is —N<, or —NH—;
- and when X is —N< then Y is —CH═ or —CH2-;
- L1 is a direct bond or a bivalent radical selected from —C1-6alkanediyl-NH—, —NH— or —NH—C1-6alkanediyl-NH—;
- L2 is a direct bond or a bivalent radical selected from —C1-6alkanediyl-, —C2-6alkenediyl-, carbonyl or —C1-6alkanediyl-substituted with one substituent selected from hydroxy or aryl;
- R1 is hydrogen, nitro, halo or amino;
- R2 is hydrogen, C1-6alkyl or arylC1-6alkyl;
- the central
- moiety may also be bridged with an ethylene bridge;
- Z is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, aryloxy, amino, cyano, arylC1-6alkylamino or benzthiazolyl(C1-6alkyl)amino or
- a ring system selected from
- wherein R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy or trihalomethyl;
- aryl is phenyl, or phenyl substituted with one or two substituents each independently selected from halo, C1-6alkyl or C1-6alkyloxy.
13 more elements
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
- n is 0, 1, 2 or 3;
- Q is —C(═O)—;
- each X is independently —N< or —CH<;
- and when X is —CH< then Y is —N<, or NH—;
- and when X is —N< then Y is —CH═ or —CH2-;
- L1 is a direct bond or a bivalent radical selected from —C1-6alkanediyl-NH—, —NH— or —NH—C1-6alkanediyl-NH—;
- L2 is a direct bond or a bivalent radical selected from —C1-6alkanediyl-, —C2-6alkenediyl-, carbonyl or —C1-6alkanediyl-substituted with one substituent selected from hydroxy or aryl;
- R1 is hydrogen, nitro, halo or amino;
- R2 is hydrogen, C1-6alkyl or arylC1-6alkyl;
- the central
- moiety may also be bridged with an ethylene bridge;
- Z is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, aryloxy, amino, cyano, arylC1-6alkylamino or benzthiazolyl(C1-6alkyl)amino or
- a ring system selected from
- wherein R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy or trihalomethyl;
- and
- aryl is phenyl, or phenyl substituted with one or two substituents each independently selected from halo, C1-6alkyl or C1-6alkyloxy.
14 more elements
Dependencies are inferred from the claim text.