Dihydropyridophthalazinone inhibitors of poly(ADP-ribose)polymerase (PARP) for use in treatment of diseases associated with a PTEN deficiency

A method of treating a disease associated with a PTEN deficiency ameliorated by the inhibition of PARP, wherein the disease associated with a PTEN deficiency is eudometrial carcinoma, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula (II):

• wherein:
• Y is an aryl or heteroaryl group optionally substituted. with 1, 2, or 3 R6;
• Z is an aryl group optionally substituted with 1, 2, or 3 R6;
• A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and aloxyalkyl, wherein C1-C6alkyl, C3-C8- cycloalkyl, alkoxy, and alkoxyalkyl are optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, and C3C8cycloalkyl, wherein B is not OH;
• R6 is selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, C3-C8heterocycloalkyl, C2-C6alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, C3-C8cycloalkylalkyl, haloalkoxy, haloalkyl, hydroxyalkylene, oxo, heteroaryl, heteroarylalkoxy, heteroaryloxy, heteroarylthio, heteroarylalkylthio, heterocycloalkoxy, C3-C8heterocycloalkylthio, heterocyclooxy, heterocyclothio, NRARB, (NRARB)C1-C6alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• R2 is selected from the group consisting of hydrogen, Br, Cl, I, and F;
• RA and RB are independently selected from the group consisting of hydrogen, C1-C6alkyl, C3-C8cycloalkyl, and alkylcarbonyl;
• or RA and RB taken together with the atom to which they are attached form a 3-10 membered heterocycle ring optionally having one to three heteroatoms or hetro functionalities seleted from the group consisting of —O—, —NH, —N(C1-C6alkyl)-, —NCO(C1-C6alkyl)-, —NCO(C3-C8cycloalkyl)- —N(aryl)-, —N(aryl-C1-C6alkyl-)-, —N(substitited-aryl-C1C6alkyl-)-, —N(heteroaryl)-, —N(heteroaryl -C1-C6alkyl-)-, —N(substituted-heteroaryl-C1-C6alkyl-)-, and —S— or S(O)q-, wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 1, 2, 3, or 4 substitnents independently selected from C2-C10-alkenyl, C1-C10-alkoxy, C1-C10alkyl, C1-C10-alkoxycarbonyl, C1-C10 alkyl, C1-C10-alkylcarbonyl, C1-C10-alkylcarbonyloxy, C1-C10-alkylthio, C1-C10-alkylthio-C1C10-alkyl, C2-C10-alkynyl, carboxy, cyano, formyl, C1C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, C1-C10-hydroxyalkylene, mercapto, nitro, —NRARB, and —(NRARB)carbonyl;
• or
• a single isomer, stereoisomer, or enantiomer, or mixture thereof, optionally as a salt solvate, chemically protected form or prodrug thereof.

A method of treating a disease associated with a PTEN deficiency ameliorated by the inhibition of PARP, wherein the disease associated with a PTEN deficiency is endometrial carcinoma, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound selected from the group consisting of:

• 8,9-diphenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phtalazin-3(7H)-one,
• 8,9bis(4-methylamino)methyl)phenyl-8,9-dihydro-2H-pyrido [4,3,2-de]phtalazin-3(7H)-one,
• 8,9-di(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-di(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-di(pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-isopropyl-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((methylamino)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((dimethylamino)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((methylamino)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4((methylamino)methyl)phenyl)-9-phenyl-8,9-dihydro-2H- pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bi(3-((methylamino)methyl)phenyl)-8,9-dihydo)-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-4-(hydroxymethyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bis(3-(4-(isobutyrylpiperazine-1-carbonyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]pthalazin-3(7H)-one,
• 9-(piperidin-3-yl)-8-(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(piperidin-4-yl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bis(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8(4-((methylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-(hydromethyl)phenyl)-9-(4-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 8(4((dimethylamino)methyl)phenyl)-9-(4-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8,9-dihydro-2H-pyrdio[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido [4,3,2-de]pthalazin-3(7H)-one,
• 9(3-(4-(cyclopropanecarbonyl)piprazine-1-carbonyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido [4,3,2-de]phthhalazin-3(7H)-one,
• 9-(3-((dimethylamino)methyl)phenyl)-8phenyl-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 8-(3-((methylamino)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-(morpholinomethyl)phenyl)-9-phenyl-8,9-dihydro 2H pyrido[4,3,2 de]phthalazin 3(7H) one,
• 8-(4-(hydroxymethyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]pthalazin-3(7H)-one,
• 9(3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-(4-((dimethylamino(methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-8-(4-(hydroxymethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthatalin-3(7H)-one,
• 9-(4-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8-(4-((methylamino)methyl)phemyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H-one,
• 9-(3-((dimethylamino)methyl)phenyl)-8-(pyridin,4-yl)-8,9-dihyro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((methylamino)methyl(phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((dimethylamimo)methyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one;
• 9-(3-(hydroxymethyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one;
• 9-(4-((methylamino)methyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((dimethylaminio)methyl)phenyl)-8-(pyridin-3-yl)-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((methylamino)methyl)phenyl)-8-(pyridin-3-yl)-8,9-dihydro -2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((dimethylamino)methyl)phenyl)-8-(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((methylamino)methyl)phenyl)-8-(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-(hydroxymethyl)phenyl)-8-(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((dimethylamino)methyl)phenyl)-8-(pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((methylamino)methyl)phenyl)-8-(pyridin-2-yl)-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-(hydroxymethyl)phenyl)-8-(pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((dimethylamino)methyl)phenyl)-8-(pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((methylamino)methyl)phenyl)-8-(pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-9-phenyl-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3((dimethylamino)methyl)phenyl)-5-fluoro-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoru-9-(3-((methylamino)methyl)phenyl)-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((dimethylamino)methyl)phenyl)-5-fluoro-8-(pyridin-4-yl)- 8,9-dihydro -2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-8,9-diphenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-((dimethylamino)methyl)phenyl)-5-fluoro-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-one,
• 5-fluoro-9-(4-((methylamino)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-one,
• 9-(3-((dimethylamino)methyl)phenyl)-5-fluoro-8-phenyl-8,9-dihydro-2H-pyiido[4,3,2-de]phthalazin-one,
• 8-(4-((dimethylamino)methyl)phenyl)-5-fluoro-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-one,
• 5-fluoro-9-(3-((methylamino)methyl)phenyl)-8-phenyl-,8,9-dihydro-2H-pyrido[4,3,2de]phthalazin-one,
• 5-fluoro-8-(4-((methylamino)methyl)phenyl)-9-phenyl-8,9-dihydro -2H-pyrido[4,3,2-de]phthalazin-one,
• 7-methyl-8,9- diphenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 7-ethyl-8,9-diphenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-9-(1-methyl-1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-isopropyl-1H-imidazol-5-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-methyl-1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H) one,
• 8-phenyl-9-(thiazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(furan-3-yl)-8,9-dihydro-2H-pyrido[4,3,2de]phthalazin 3(7H)-one,
• 8-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrdo[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(4-(piperazin-1-ylmethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalzin-3(7H)-one,
• 8-(1-methyl-1H-imidazol-2-yl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-methyl-1H--imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bis(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-ethyl-1H-imidazol-2-2yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-phenyl-9-(1-propyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-methyl-1H-imidazol-5-yl)8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phathalazin-3(7H)-one,
• 9-(3-((diethylamino)methyl)phenyl)-8-(4-((diethylamino)methyl)phenyl)8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((4-methylpiperazin-1-yl) methyl)phenyl)-8-phenyl-8,9-dihydro-2H -pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(pyridin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(piperidin-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(pyridin-2-yl))-8,9-dihydro-2H-pryido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4((4-methylpiperazin-1-yl)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bis(4-flurophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8(4-fluorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bis(3-((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(3-((cyclopropylamino)methyl)phenyl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(3-((dimethylamino)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(3-(morpholinomethyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin3(7H)-one,
• 8-(4-(azetidin-1-ylmethyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-methyl-1H-1,2,4-triazol-5-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-methyl-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-(1,4,5-trimethy 1-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,3-triazol-4-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-8-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-chlorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-methyl-1H-imidazol-2-yl)-8-(4-(trifluoromethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-(thiazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-ethyl-1H-imidazol-2-yl)-8-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one
• 8-(4-((4-ethyl-3-methylpiperazin-1-yl)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(4-(piperazin-1-ylmethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(4-((3-methylpiperazin-1-yl)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(4-(pyrrolidin-1-ylmethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-Fluorophenyl)-9-(4-methyl-4H-1,2,4-triazol-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-(1-methyl-1H-imidazo[4,5-c]pyridin-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-chloro-9-(1-methyl-1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-5-fluoro-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8,9-bis(4-((dimethylamino)methyl)phenyl)-5-fluoro-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-5-fluoro-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((3,4-dimethylpiperazin-1-methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((3,5-dimethylpiperazin-1-yl)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-phenyl-8-(4-(pyrrolidin-1-ylmethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(1-methyl-1H-imidazol-2-yl)-8-(4-(pyrrolidin-1-ylmethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(quinolin-6-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one;
• 8-(4-((dimethylamino)methyl)phenyl)-9-p-tolyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-chlorophenyl)-8-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(4-methoxyphenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((diethylamino)methyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((diethylamino)methyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-chlorophenyl)-8-(4-((diethylamino)methyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-9-(4-fluorophenyl)-8-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(4-ethylphenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(4-isopropylphenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((dimethylamino)methyl)phenyl)-9-(4-(trifluoromethyl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-((diethylamino)methyl)phenyl)-9-p-tolyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(4-(1-methylpyrrolidin-2-yl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(4-(pyrrolidin-2-yl)phenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 8-(4-fluorophenyl)-9-methyl-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-8-(1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• 9-(4-fluorophenyl)-9-hydroxy-8-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-one,
• 8-(4-(azetidin-1-ylmethyl)phenyl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one, and
• 5-fluora-8-(1-methyl-1H-imidazol-2-yl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one;
• or a pharmaceutically acceptable salt, solvate or prodrug thereof.

A method of treating a disease associated with a PTEN deficiency ameliorated by the inhibition of PARP, wherein the disease associated with a PTEN deficiency is endometrial carcinoma, comprising administering to a subject in need of treatment a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula (I):

• wherein
• Y and Z are each independently selected from the group consisting of:
• a) an aryl group optionally substituted with 1, 2, or 3 R6;
• b) a heteroaryl group optionally substituted with 1, 2, or 3 R5;
• and
• c) a substituent independently selected from the group hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocyloalkylalkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NRARB)alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, NRARBalkylene, and (NRARB)carbonyl;
• A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cyclcoalkyl, alkoxy, and alkoxyalkyl, wherein C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl are independently optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, and C3-C8cycloalkyl, wherein B is not OH;
• RA and RB an independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, and alkylcarbonyl;
• or RA and RB taken together with the atom to which they are attached form a 3-10 membered heterocycle ring optionally having one to three heteroatoms or hetero functionalities selected from the group consisting of —O—, —NH, —N(C1-C6-alkyl)-, —NCO(C1-C6alkyl)-, —N(aryl)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, and —S— or S(O)q—,
• wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C2-C10-alkenyl, C1-C10-alkoxy, C1C10-alkoxy-C1-C 10-alkyl, C1-C10-alkoxycarbonyl, C1-C10-alkyl, C1-C10alkylcarbonyl, C1-C10-alkylcarbonyloxy, C1-C10-alkylthio, C1-C10-alkylthio-C1-C10-alkyl, C2-C10-alkynyl, carboxy, cyano , formyl, C1C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, Cl-C10-hydroxyalkylene, mercapto, nitro, —NRARB, and (NRARB)carbonyl;
• R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl, hydroxyalkylene, and (NRARB)alkylene;
• and each R6 is selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, C3-C8heterocycloalkyl, C2-C6alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, C3-C8cycloalkylalkyl, haloalkoxy, haloalkyl, hydroxyalkylene, oxo, heteroaryl, heteroarylalkoxy, heteroaryloxy, heteroarylthio, heteroarylalkylthio, heterocycloalkoxy, C3-C8heterocycloalkylthio, heterocyclooxy, heterocyclothio, NR ARB, (NRARB)C1-C6alkylene, (NRA,RB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• or a single isomer, stereoiosomer, or enantiomer, or mixture thereof;
• or a pharmaceutically acceptable salt pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug, and a pharmaceutically acceptable carrier, excipient, binder or diluent thereof.

A method of treating a cancer associated with a PTEN deficiency, wherein the cancer associated with a PTEN deficiency endometrial carcinoma, wherein said endometrial carcinoma is deficient in Homologous Recombination (HR) dependent DNA double strand break (DSD) repair pathway, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula (I);

• wherein:
• Y and Z are each independently selected from the group consisting of:
• a) an aryl group optionally substituted with 1, 2, or 3 R6;
• b) a heteroaryl group optionally substituted with 1, 2, or 3 R6;
• and
• c) a substituent independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarboaylalkyl, alkyl, alkalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocycloalkylalkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NRARB)alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkenyl, akkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, NRARBalkylene, and (NRARB)carbonyl;
• A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl, wherein C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl are independently optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, and C3-C8cycloalkyl, wherein B is not OH;
• RA and RB are independently selected from the group of hydrogen, alkyl, cycloalkyl, and alkylcarbonyl;
• or RA and RB taken together with the atom to which they are attached form a 3-10 membered heterocycle ring optionally having one to three heteroatoms or hetero functionalities selected from the group consisting of —O—, —NH, —N(C1-C6-alkyl)-, —NCO(C1-C6-alkyl)-, —N(aryl)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, and —S— or S(O)q-,
• wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C2-C10-alkenyl, C1-C10-alkoxy, C1-C10-alkoxy-C1-C10alkyl, C1-C10alkoxycarbonyl, C1-C10-alkyl, C1-C10-alkylcarbonyl, C1-C10-alkycarbonyloxy, C1-C10-alkylthio, C1-C10-alkyl, C2-C10-alkynyl, carboxy, cyano, formyl, C1-C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, C1-C10-hydroxyalkylene, mercapto, nitro, —NRARB, and (NRARB)carbonyl;
• R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl, hydroxyalkylene, and (NRARB)alkylene;
• and each R6 is selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, C3-C8heterocycloalkyl, C2-C6alkenyl, alkoxy, alkoxyalkyl, alkexycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, C3-C8cycloalkylalkyl, haloalkoxy, halolkyl, hydroxyalkylene, oxo, heteroaryl, heteroarylalkoxy, heteroaryloxy, heteroarylthio, heteroarylalkylthio, heterocycloalkoxy. C3-C8heterocycloalkylthio, heterocyclooxy, heterecyclothio, NHARB, (NRARB)C1-C6alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene or a single isomer, stereoisomer, or enantiomer, or mixture thereof, optionally as a salt, solvate, chemically protected form or prodrug thereof.

A method of treating a disease associated with a PTEN deficiency, wherein the disease associated with a PTEN deficiency is endometrial carcinoma, wherein said endometrial carcinoma is associated with an abrogated or reduced ability to control the phosphoinositide 3-kinase signaling pathway comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula (I):

• wherein:
• Y and Z arc each independently selected from the group consisting of:
• a) an aryl group optionally substituted with 1, 2, or 3 R6;
• b) a heteroaryl group optionally substituted with 1, 2, or 3 R6;
• and
• c) a substituent independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocycloalkylalkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NHARB)alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, NRARBalkylene, and (NRARB)carbonyl;
• A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl, wherein C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl are independently optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, and C3-C8cycloalkyl, wherein B is not OH;
• RA and RB are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, and alkylcabbonyl, or RA and RB taken together with the atom to which they are attached form a 3-10 membered heterocycle ring optionally having one to three heteroatoms or hetero functionalities selected from the group consisting of —O—, —NH, —N(C1-C6-alkyl)-, —NCO(C1C6-alkyl)-, —N(aryl)- —N(aryl-C1-C6-alkly-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, and —S— or S(O)q-, wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C2-C10-alkenyl, C1-C10-alkoxy, C1-C10alkoxy-C1-C10-alkyl, C1-C10-alkoxycarbonyl, C1-C10-alkyl, C1-C10-alkylcarbonyl, C1-C10-alkylcarbonyloxy, C1-C10-alkylthio, C1-C10-alkylthio-C1-C10-alkyl, C2-C10-alkynyl, carboxy, cyano, formyl, C1-C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, C1-C10- hydroxyalkylene, mercapto, nitro, —NRARB and (NRARB)carbonyl;
• R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl, hydroxyalkylene and (NRARB)alkylene;
• and each R6 is selected from the group consisting of CH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, C3-C8heterocycloalkyl, C2-C,6alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, C3-C8cycloalkylalkyl, haloalkoxy, haloalkyl, hydroxyalkylene, oxo, heteroaryl, heteroarylalkoxy, heteroaryloxy, heteroarylthio, heteroarylalkylthio, heterocycloalkoxy, C3-C8heterocycloalkylthio, heterocyclooxy, heterocyclothio, NRARB, (NRARB)C1-C6alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• or a single isomer, stereoisomer, or enantiomer, or mixture thereof, optionally as a salt, solvate, chemically protected form or prodrug thereof.

A method of treating a disease associated with a PTEN deficiency, wherein the disease associated with a PTEN deficiency is endometrial carcinoma, wherein said endometrial carcinoma is due to abnormal regulation of centromere stability comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula. (I):

• wherein:
• Y and Z are each independently selected from the group consisting of:
• a) an aryl group optionally substituted with 1, 2, or 3 R6;
• b) a heteroaryl group optionally substituted with 1, 2, or 3 R6;
• and
• c) a substituent independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxyearbonylalkyl, alkyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocycloalkylakyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NRARB)alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• R1,R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkenyl, alkomy, aloxycarbonyl, alkyl, cycloalkyl, alknyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, NRARBalkylene, and (NRARB)carbonyl;
• A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl, wherein C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl are independently optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, CI, F, I, C1-C6alkyl, and C3-C8cycloalkyl, wherein B is not OH;
• RA and RB are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, and alkylcarbonyl;
• or RA and RB taken together with the atom to which they are attached form a 3-10 membered heterocycle ring optionally having one to three heteroatoms or hetero functionalities selected from the group consisting of —O—, —NH, —N(C1-C6-alkyl)-, —NCO(C1-C6-alkyl)-, —N(aryl)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-)-, —N(heteroaryl)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, and —S— or S(O)q-, wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C2-C10alkenyl, C1-C10alkoxy, C1-C10-alkoxy-C1-C10-alkyl, C1-C10-alkoxycarbonyl, C1-C10-alkyl, C1-C10-alkylcarbonyl, C1-C10-alkylcarbonyloxy, C1-C10-alkylthio, C1-C10-alkylthio-C1-C10alkyl, C2-C10-alkynyl, carboxy, cyano, fomyl, C1-C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, C1-C10-hydroxyalkylene, mercapto, nitro, —NRARB, and (NRARB)carbonyl;
• R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl, hydroxyalkylene, and (NRARB)alkylene;
• and each R6 is selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, C3-C8heterocycloalkyl, C2-C6alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, C3-C8cycloalkylalkyl, haloalkoxy, haloalkyl, hydroxyalkylene, oxo, heteroaryl, heteroarylalkoxy, heteroaryloxy, heteroarylthio, heteroarylthio, heterocycloalkoxy, C3-C8heterocycloalkylthio, heterocyclooxy, heterocyclothio, NRARB, (NRARB)C1-C6alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;
• or a single isomer, stereoisomer, or enantiomer, or mixture thereof, optionally as a salt, solvate, chemically protected form or prodrug thereof.

A method of treating a disease associated with a PTEN deficiency ameliorated by the inhibition of PARP, wherein the disease associated with a PTEN deficiency is endometrial carcinoma, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound selected from the group consisting of:

• (8S,9R)-5-fluoro-9-(1-methyl-1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[1,3,2de]phthalazin-3(7H)-one,
• (8R,9S)-5-fluoro-9-(1-methyl-1H-imidazol-2-yl)-8-phenyl-8,9-dihydro-2H-pyrido[1,3,2de]phthalazin-3(7H)-one,
• (8S,9R)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthatazn-3(7H)-one,
• (8S,9S)-5-fluoro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8-phenyl-,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8R,9S)-8-(4-fluorophenyl)-9-(1-methyl-1H-imidzol-2-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8S,9R)-8-(4-fluorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H-pyrido-[4,3,2-de]phthalazin-3-(7H)-one,
• (8R,9S)-5-fluoro-8-(1-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido [4,3,2-de]phthalazin-3(7H)-one,
• (8R,9S)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H -pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8S,9S)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-imidazol-2-yl)-8,9-dihydro-2H -pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8R,9S)-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8S,9R)-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8R,9S)-8-(4-((dimethylamino)methyl)phenyl)-5-fluoro-9-(1-triazol-5-yl)-8,9-dihydro-H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8S,9R)-8-(4-((dimethylamino)methyl)phenyl)-5-fluoro-9- (1-methyl-1H-1,2,4-triazol-5-yl)8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one,
• (8R,9S)-8-(4-(azetidin-1-ylmethyl)phenyl)-9-(4-fluorophenyl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one, and
• (8S,9R)-8-(4-(azetidin-1-ylmethyl)phenyl)-9-4-fluorophenyl)-8,9-dihydro-2H-pyridoi[4,3,2-de]phthalazin-3(7H)-one, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

A method of treating astrocytoma;

• endometroid serous adenocarcinoma, endometroid clear cell adenocarcinoma, endometroid adenosquamous carcinoma, or mixed histology;
• and small cell comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula (I):
• wherein:
• Y and Z are each independently selected from the group consisting of:
• a) an aryl group optionally substituted with 1, 2, or 3 R6;
• b) a heteroaryl group optionally substituted with 1, 2, or 3 R6;
• and
• c) a substituent independently selected from the group consisting of hydrogen, alkonyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocycloalkylalkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NRARB)alkylene, (NRARB)carbonyl, (NRARB)carbonaylkylene, (NRARB)sulfonyl, and (NRARBsulfonylalkylene;
• R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkenyl, alkoxy, aloxycarbonyl, alkyl, cycloalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, NRARBalkylene, and (NRARB)carbonyl;
• A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl, wherein C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl are independently optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, and C3-C8cycloalkyl, wherein B is not OH;
• RA and RB are indepepdently selected from the group consisting of hydrogen, alkyl, cycloalkyl, and alkylcarbonyl;
• or RA and RB taken together with the atom to which they are attached from a 3-10 membered heterocycle ring optionally haviug one to three heteroatoms or hetero functionalities seleted from the group consisting of —O—, —NH, —N(C1-C6alkyl)-, —NCO(C1-C6-alkyl)-, —N(arly)-, —N(aryl-C1-C6-alkyl-)-, —(substituted-aryl-C1C6alkyl-)-, —N(heteroaryl)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, and —S— or S(O)q-,
• wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 0, 1, 2, 3, or 4 substituents independently selected from C2-C10alkenyl, C1-C10-alkoxy, C1-C10-alkoxy-C1-C10-alkyl, C1-C10-alkoxycarbonyl, C1-C10-alkyl, C1-C10-alkylcarbonyl, C1-C10-alkylthio, C1-C10alkylthio-C1-C10alkyl, C2-C10-alkynyl, carboxy, cyano, formyl, C1-C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, C1-C10-hydroxyalkylene, mercapto, nitro, —NRARB, and (NRARB)carbonyl;
• R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl, hydroxyalkylene, and (NRARB)alkylene:
• and
• each R6 is selected from the group consisting of OR, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, C3-C8hetercoyeloalkyl, C2-C6alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, C3-C8cycloalkylakyl, haloalkoxy, haloalkyl, hydroxyalkylene, oxo, hetetoaryl, heteroarylalkoxy, heteroaryloxy, heteroaryl thio, heteroarylalkylthio, heterocycloalkoxy, C3-C8heterocycloalkylthio, heterocyclooxy, heterocyclothio, NRARB, (NRARB)C1-C6alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonyalkylene;
• or
• a single isomer, stereoisomer, or enantionier, or mixture thereof, optionally as a salt, solvate, chemically protected form or prodrug thereof.