2-Amino-quinazolin-5-ones

{
  "publication_number": "US2007027150A1",
  "country": "US",
  "kind": "A1",
  "title": "2-Amino-quinazolin-5-ones",
  "abstract": "2-Amino-quinazolin-5-one compounds, stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the 2-amino-quinazolin-5-one compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the 2-amino-quinazolin-5-one compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cell proliferative diseases.",
  "claims": [
    "1. A compound having formula (I): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n is 0 or 1; wherein when n is 1, X is C, Y is at each position independently selected from CQ 1 and N, and Z is selected from CR 2 and N, and wherein when n is 0, X is C or N, Y is at each position independently selected from CQ 1, N, NQ 2, O, and S; wherein each Q 1 is independently selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, (4) substituted or unsubstituted C 2 -C 6 alkenyl, (5) substituted or unsubstituted C 2 -C 6 alkynyl, (6) substituted or unsubstituted C 3 -C 7 cycloalkyl, (7) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (8) substituted or unsubstituted aryl, (9) substituted or unsubstituted heteroaryl, (10) substituted or unsubstituted heterocyclyl, (11) substituted or unsubstituted amino, (12) - OR 3, - SR 3, or - N(R 3) 2, (13) - C(O)R 3, - CO 2 R 3, - C(O)N(R 3) 2, - S(O)R 3, - SO 2 R 3, or - SO 2 N(R 3) 2, (14) - OC(O)R 3, - N(R 3)C(O)R 3, or - N(R 3)SO 2 R 3, (15) - CN, and (16) - NO 2; wherein each Q 2 is independently selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C 1 -C 6 alkyl, (3) substituted or unsubstituted C 2 -C 6 alkenyl, (4) substituted or unsubstituted C 2 -C 6 alkynyl, (5) substituted or unsubstituted C 3 -C 7 cycloalkyl, (6) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, and (9) substituted or unsubstituted heterocyclyl; wherein R 1 is selected from the group consisting of (1) hydrogen, (2) halogen, (3) hydroxyl, (4) C 1 -C 6 alkoxy, (5) thiol, (6) C 1 -C 6 alkylthiol, (7) substituted or unsubstituted C 1 -C 6 alkyl, (8) amino, alkylamino, arylamino, or aralkyl amino, (9) substituted or unsubstituted aryl, (10) substituted or unsubstituted heteroaryl, and (11) substituted or unsubstituted heterocyclyl; wherein R 2 is selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, and (4) - OR 3, - SR 3, or - N(R 3) 2; wherein R 4 and R 5 are independently selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, (4) - OR 3, - SR 3, or - N(R 3) 2, and (5) - OC(O)R 3, - N(R 3)C(O)R 3, or - N(R 3)SO 2 R 3; wherein each R 3 is independently selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C 1 -C 6 alkyl, (3) substituted or unsubstituted C 2 -C 6 alkenyl, (4) substituted or unsubstituted C 2 -C 6 alkynyl, (5) substituted or unsubstituted C 3 -C 7 cycloalkyl, (6) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, (9) substituted or unsubstituted heterocyclyl, and (10) substituted or unsubstituted amino; and with the proviso that when R 1 is methyl, and R 4 and R 5 are hydrogen, then X, Y, Z, and n together do not form an unsubstituted phenyl or furan-2-yl ring, and with the proviso that when R 1, R 4, and R 5 are hydrogen, then X, Y, Z, and n together do not form a furan-2-yl, thien-2-yl, or phenyl ring wherein said ring is unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, amino, alkylamino, dialkylamino, hydroxyl, and halo. 2. A compound of claim 1, wherein R 1 is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl. 3. A compound of claim 2, wherein R 1 is methyl. 4. A compound of claim 1, wherein R 2 is hydrogen or fluoro. 5. A compound of claim 1, wherein R 4 is hydrogen. 6. A compound of claim 1, wherein R 5 is hydrogen. 7. A compound according to claim 1, wherein at least one of Q 1, Q 2, R 2, or R 3 is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, substituted or unsubstitued C 3 -C 7 cycloalkyl, and substituted or unsubstitued C 5 -C 7 cycloalkenyl. 8. A compound of claim 7, wherein said aryl, heterocyclyl, heteroaryl, C 3 -C 7 cycloalkyl, and C 5 -C 7 cycloalkenyl is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, imidazolyl, triazolyl, indolyl, oxadiazole, thiadiazole, furanyl, quinolinyl, isoquinolinyl, isoxazolyl, oxazolyl, thiazolyl, morpholino, piperidinyl, pyrrolidinyl, thienyl, cyclohexyl, cyclopentyl, cyclohexenyl, and cyclopentenyl. 9. A compound of claim 8, wherein one of Q 1 or Q 2 is selected from the group consisting of (2-hydroxy-ethylamino)-pyrazin-2-yl, 1-methyl-1H-pyrazol-4-yl, 2-(5-methyl-pyridin-2-yl)-phenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,4-dimethoxyphenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 2,6-dimethyl-pyridin-3-yl, 2-acetamidophenyl, 2-aminocarbonylphenyl, 2-amino-pyrimidin-5-yl, 2-chloro-4-methoxy-pyrimidin-5-yl, 2-chloro-5-fluoro-pyridin-3-yl, 2-chloro-phenyl, 2-chloro-pyridin-3-yl, 2-chloro-pyridin-3-yl, 2-chloro-pyridin-4-yl, 2-difluoro-3-methoxyphenyl, 2-ethyl-phenyl, 2-fluoro-3-methoxy-phenyl, 2-fluoro-3-methylphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-4-methyl-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-5-methylphenyl, 2-fluorophenyl, 2-fluoro-pyridin-3-yl, 2-hydroxymethyl-3-methoxyphenyl, 2-hydroxymethylphenyl, 2-methoxy-5-trifluoromethyl-phenyl, 2-methoxyphenyl, 2-methoxy-pyridin-3-yl, 2-methoxy-pyrimidin-4-yl, 2-methylphenyl, 2-methyl-pyridin-3-yl, 2-oxo-1,2-dihydro-pyridin-3-yl, 2-phenoxyphenyl, 2-trifluoromethoxyphenyl, 3,5-dimethyl-isoxazol-4-yl, 3,6-dimethyl-pyrazin-2-yl, 3-acetamidophenyl, 3-aminocarbonylphenyl, 3-bromo-phenyl, 3-chloro-pyrazin-2-yl, 3-cyanophenyl, 3-dimethylaminophenyl, 3-ethoxy-phenyl, 3-ethyl-4-methyl-phenyl, 3-ethynyl-phenyl, 3-fluoro-6-methoxy-pyridin-2-yl, 3-fluoro-6-methoxy-pyridin-2-yl, 3-fluorophenyl, 3-fluoro-pyrazin-2-yl, 3-methanesulfonamidophenyl, 3-methoxycarbonylphenyl, 3-methoxyphenyl, 3-methoxy-pyrazin-2-yl, 3-methyl-3H-imidazo[4,5-b]pyrazin-5-yl, 3-methylphenyl, 3-methyl-pyridin-2-yl, 3-trifluoromethoxyphenyl, 3-trifluoromethoxy-phenyl, 3-trifluoromethylphenyl, 4,5-dimethoxy-pyrimidin-2-yl, 4,5-dimethoxy-pyrimidin-2-yl, 4-amino-5-fluoro-pyrimidin-2-yl, 4-chloro-2,5-dimethoxy-phenyl, 4-chloro-2-fluoro-phenyl, 4-chloro-2-methoxy-5-methyl-phenyl, 4-chloro-pyridin-3-yl, 4-ethoxy-pyrimidin-5-yl, 4-ethyl-1H-pyrazol-3-yl, 4-fluorophenyl, 4-methoxy-5-methyl-pyrimidin-2-yl, 4-methoxy-5-methyl-pyrimidin-2-yl, 4-methoxy-5-methyl-pyrimidin-2-yl, 4-methoxy-pyridin-3-yl, 4-methoxy-pyrimidin-2-yl, 4-methoxy-pyrimidin-5-yl, 4-methyl-pyridin-2-yl, 4-methyl-pyridin-3-yl, 5,6-dimethoxy-pyrazin-2-yl, 5-acetyl-thiophen-2-yl, 5-amino-6-methoxy-3-methyl-pyrazin-2-yl, 5-amino-6-methoxy-pyrazin-2-yl, 5-chloro-4-methoxy-pyrimidin-2-yl, 5-chloro-6-methoxy-pyrazin-2-yl, 5-fluoro-2-methoxyphenyl, 5-fluoro-4-methoxy-pyrimidin-2-yl, 5-fluoro-6-methoxy-pyrazin-2-yl, 5-fluoro-pyridin-2-yl, 5-methoxy-pyridin-3-yl, 5-trifluoromethyl-pyrimidin-2-yl, 6-acetyl-pyridin-2-yl, 6-chloro-pyrazin-2-yl, 6-ethoxy-pyrazin-2-yl, 6-ethyl-pyridin-2-yl, 6-fluoro-pyridin-2-yl, 6-fluoro-pyridin-3-yl, 6-hydroxy-pyridin-2-yl, 6-methoxy-5-methyl-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-methoxy-pyridin-2-yl, 6-methoxy-pyridin-3-yl, 6-methylamino-pyrazin-2-yl, 6-methyl-pyridin-2-yl, and 6-trifluoromethyl-pyridin-2-yl. 10. A compound of claim 1, wherein R 3 is selected from the group consisting of methyl, ethyl, isopropyl, cyclopentyl, and cyclohexyl. 11. A compound of claim 1, wherein R 3 is selected from the group consisting of substituted and unsubstituted phenyl, substituted and unsubstituted thiazolyl, substituted and unsubstituted pyridyl, substituted and unsubstituted pyrazinyl, and substituted and unsubstituted pyrimidinyl. 12. A compound of claim 1, wherein R 3 is selected from the group consisting of 2-aminoethyl, 2-piperidinylethyl, 2-piperazinylethyl, 2-morpholinylethyl, and 2-(N-methylpiperazinyl)ethyl. 13. A compound of claim 1 having formula (Ia) wherein R 1, R 4, R 5, X, Y, Z, and n are previously defined. 14. A compound of claim 1 having formula II wherein W 1 and W 2 are independently N or CQ 1; wherein R 6 is selected from the group consisting of (1) substituted or unsubstituted C 3 -C 7 cycloalkyl, (2) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heteroaryl, and (5) substituted or unsubstituted heterocyclyl; wherein R 7 and R 8 are independently (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, (4) - OR 3, - SR 3, or - N(R 3) 2, and wherein Q 1, R 1, R 3, R 4, and R 5 are previously defined. 15. A compound of claim 14, wherein R 1 is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl. 16. A compound of claim 15, wherein R 1 is methyl. 17. A compound of claim 14, wherein R 4 is hydrogen. 18. A compound of claim 14, wherein R 5 is hydrogen. 19. A compound of claim 14, wherein W 1 is N. 20. A compound of claim 14, wherein W 2 is N. 21. A compound of claim 14, wherein W 1 and W 2 are CQ 1. 22. A compound of claim 21, wherein each Q 1 is hydrogen. 23. A compound of claim 14, wherein R 6 is selected from the group consisting of substituted aryl, substituted heterocyclyl, substituted heteroaryl, substituted C 3 -C 7 cycloalkyl, and substituted C 5 -C 7 cycloalkenyl, wherein said aryl, heterocyclyl, heteroaryl, C 3 -C 7 cycloalkyl, and C 5 -C 7 cycloalkenyl is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, imidazolyl, triazolyl, indolyl, oxadiazole, thiadiazole, furanyl, quinolinyl, isoquinolinyl, isoxazolyl, oxazolyl, thiazolyl, morpholino, piperidinyl, pyrrolidinyl, thienyl, cyclohexyl, cyclopentyl, cyclohexenyl, and cyclopentenyl. 24. A compound of claim 14, wherein R 6 is selected from the group consisting of (2-hydroxy-ethylamino)-pyrazin-2-yl, 1-methyl-1H-pyrazol-4-yl, 2-(5-methyl-pyridin-2-yl)-phenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,4-dimethoxyphenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 2,6-dimethyl-pyridin-3-yl, 2-acetamidophenyl, 2-aminocarbonylphenyl, 2-amino-pyrimidin-5-yl, 2-chloro-4-methoxy-pyrimidin-5-yl, 2-chloro-5-fluoro-pyridin-3-yl, 2-chloro-phenyl, 2-chloro-pyridin-3-yl, 2-chloro-pyridin-3-yl, 2-chloro-pyridin-4-yl, 2-difluoro-3-methoxyphenyl, 2-ethyl-phenyl, 2-fluoro-3-methoxy-phenyl, 2-fluoro-3-methylphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-4-methyl-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-5-methylphenyl, 2-fluorophenyl, 2-fluoro-pyridin-3-yl, 2-hydroxymethyl-3-methoxyphenyl, 2-hydroxymethylphenyl, 2-methoxy-5-trifluoromethyl-phenyl, 2-methoxyphenyl, 2-methoxy-pyridin-3-yl, 2-methoxy-pyrimidin-4-yl, 2-methylphenyl, 2-methyl-pyridin-3-yl, 2-oxo-1,2-dihydro-pyridin-3-yl, 2-phenoxyphenyl, 2-trifluoromethoxyphenyl, 3,5-dimethyl-isoxazol-4-yl, 3,6-dimethyl-pyrazin-2-yl, 3-acetamidophenyl, 3-aminocarbonylphenyl, 3-bromo-phenyl, 3-chloro-pyrazin-2-yl, 3-cyanophenyl, 3-dimethylaminophenyl, 3-ethoxy-phenyl, 3-ethyl-4-methyl-phenyl, 3-ethynyl-phenyl, 3-fluoro-6-methoxy-pyridin-2-yl, 3-fluoro-6-methoxy-pyridin-2-yl, 3-fluorophenyl, 3-fluoro-pyrazin-2-yl, 3-methanesulfonamidophenyl, 3-methoxycarbonylphenyl, 3-methoxyphenyl, 3-methoxy-pyrazin-2-yl, 3-methyl-3H-imidazo[4,5-b]pyrazin-5-yl, 3-methylphenyl, 3-methyl-pyridin-2-yl, 3-trifluoromethoxyphenyl, 3-trifluoromethoxy-phenyl, 3-trifluoromethylphenyl, 4,5-dimethoxy-pyrimidin-2-yl, 4,5-dimethoxy-pyrimidin-2-yl, 4-amino-5-fluoro-pyrimidin-2-yl, 4-chloro-2,5-dimethoxy-phenyl, 4-chloro-2-fluoro-phenyl, 4-chloro-2-methoxy-5-methyl-phenyl, 4-chloro-pyridin-3-yl, 4-ethoxy-pyrimidin-5-yl, 4-ethyl-1H-pyrazol-3-yl, 4-fluorophenyl, 4-methoxy-5-methyl-pyrimidin-2-yl, 4-methoxy-5-methyl-pyrimidin-2-yl, 4-methoxy-5-methyl-pyrimidin-2-yl, 4-methoxy-pyridin-3-yl, 4-methoxy-pyrimidin-2-yl, 4-methoxy-pyrimidin-5-yl, 4-methyl-pyridin-2-yl, 4-methyl-pyridin-3-yl, 5,6-dimethoxy-pyrazin-2-yl, 5-acetyl-thiophen-2-yl, 5-amino-6-methoxy-3-methyl-pyrazin-2-yl, 5-amino-6-methoxy-pyrazin-2-yl, 5-chloro-4-methoxy-pyrimidin-2-yl, 5-chloro-6-methoxy-pyrazin-2-yl, 5-fluoro-2-methoxyphenyl, 5-fluoro-4-methoxy-pyrimidin-2-yl, 5-fluoro-6-methoxy-pyrazin-2-yl, 5-fluoro-pyridin-2-yl, 5-methoxy-pyridin-3-yl, 5-trifluoromethyl-pyrimidin-2-yl, 6-acetyl-pyridin-2-yl, 6-chloro-pyrazin-2-yl, 6-ethoxy-pyrazin-2-yl, 6-ethyl-pyridin-2-yl, 6-fluoro-pyridin-2-yl, 6-fluoro-pyridin-3-yl, 6-hydroxy-pyridin-2-yl, 6-methoxy-5-methyl-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-methoxy-pyridin-2-yl, 6-methoxy-pyridin-3-yl, 6-methylamino-pyrazin-2-yl, 6-methyl-pyridin-2-yl, and 6-trifluoromethyl-pyridin-2-yl. 25. A compound of claim 14, wherein R 7 is hydrogen. 26. A compound of claim 14, wherein R 8 is hydrogen or fluoro. 27. A compound of claim 14 having formula (IIa) wherein R 1, R 4, R 5, R 6, R 7, R 8, W 1, and W 2 are previously defined. 28. A compound of claim 1 having formula III: or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n is 0 or 1, wherein when n is 1, X is C, Y is at each position independently selected from CQ 1 and N, and Z is selected from CR 2 and N, and wherein when n is 0, X is C or N, Y is at each position independently selected from CQ 1, N, NQ 2, O, and S; wherein Q 1 is selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, (4) substituted or unsubstituted C 2 -C 6 alkenyl, (5) substituted or unsubstituted C 2 -C 6 alkynyl, (6) substituted or unsubstituted C 3 -C 7 cycloalkyl, (7) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (8) substituted or unsubstituted aryl, (9) substituted or unsubstituted heteroaryl, (10) substituted or unsubstituted heterocyclyl, (11) substituted and unsubstituted amino, (12) - OR 3, - SR 3, or - N(R 3) 2, (13) - C(O)R 3, - CO 2 R 3, - C(O)N(R 3) 2, - S(O)R 3, - SO 2 R 3, or - SO 2 N(R 3) 2, (14) - OC(O)R 3, - N(R 3)C(O)R 3, or - N(R 3)SO 2 R 3, (15) - CN, and (16) - NO 2; wherein Q 2 is selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C 1 -C 6 alkyl, (3) substituted or unsubstituted C 2 -C 6 alkenyl, (4) substituted or unsubstituted C 2 -C 6 alkynyl, (5) substituted or unsubstituted C 3 -C 7 cycloalkyl, (6) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, and (9) substituted or unsubstituted heterocyclyl; wherein R 2 is selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 3 alkyl, (4) halo-substituted or unsubstituted - OCH 3, - SCH 3, or - NHCH 3, and wherein R 3 is at each position independently selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C 1 -C 6 alkyl, (3) substituted or unsubstituted C 2 -C 6 alkenyl, (4) substituted or unsubstituted C 2 -C 6 alkynyl, (5) substituted or unsubstituted C 3 -C 7 cycloalkyl, (6) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, (9) substituted or unsubstituted heterocyclyl, and (10) substituted and unsubstituted amino; with the proviso that when n is 1, X is C, Y is CQ 1, and Z is CR 2, Q 1, and R 2 are not both hydrogen, with the proviso that when n is 0, X is C, and Y adjacent to X is not O, and with a further proviso that the total molecular weight does not exceed 750 Daltons. 29. A compound of claim 1 having formula (IV) wherein R 9 and R 10 are independently Q 1, and R 1, R 4, R 5, Q 1, and Q 2 are previously defined. 30. A compound of claim 29 having formula (IVa) wherein R 9 and R 10 are independently Q 1, and R 1, R 4, R 5, Q 1, and Q 2 are previously defined. 31. A compound or stereoisomer, tautomer, or pharmaceutically acceptable salt thereof selected from Tables I and II. 32. A composition comprising a pharmaceutically acceptable carrier and a compound having formula (V) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein n is 0 or 1; wherein when n is 1, X is C, Y is at each position independently selected from CQ 1 and N, and Z is selected from CR 2 and N, and wherein when n is 0, X is C or N, Y is at each position independently selected from CQ 1, N, NQ 2, O, and S; wherein each Q 1 is independently selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, (4) substituted or unsubstituted C 2 -C 6 alkenyl, (5) substituted or unsubstituted C 2 -C 6 alkynyl, (6) substituted or unsubstituted C 3 -C 7 cycloalkyl, (7) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (8) substituted or unsubstituted aryl, (9) substituted or unsubstituted heteroaryl, (10) substituted or unsubstituted heterocyclyl, (11) substituted or unsubstituted amino, (12) - OR 3, - SR 3, or - N(R 3) 2, (13) - C(O)R 3, - CO 2 R 3, - C(O)N(R 3) 2, - S(O)R 3, - SO 2 R 3, or - SO 2 N(R 3) 2, (14) - OC(O)R 3, - N(R 3)C(O)R 3, or - N(R 3)SO 2 R 3, (15) - CN, and (16) - NO 2; wherein each Q 2 is independently selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C 1 -C 6 alkyl, (3) substituted or unsubstituted C 2 -C 6 alkenyl, (4) substituted or unsubstituted C 2 -C 6 alkynyl, (5) substituted or unsubstituted C 3 -C 7 cycloalkyl, (6) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, and (9) substituted or unsubstituted heterocyclyl; wherein R 1 is selected from the group consisting of (1) hydrogen, (2) halogen, (3) hydroxyl, (4) C 1 -C 6 alkoxy, (5) thiol, (6) C 1 -C 6 alkylthiol, (7) substituted or unsubstituted C 1 -C 6 alkyl, (8) amino, alkylamino, arylamino, or aralkylamino, (9) substituted or unsubstituted aryl, (10) substituted or unsubstituted heteroaryl, and (11) substituted or unsubstituted heterocyclyl; wherein R 2 is selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, and (4) - OR 3, - SR 3, or - N(R 3) 2; wherein R 4 and R 5 are independently selected from the group consisting of (1) hydrogen, (2) halogen, (3) substituted or unsubstituted C 1 -C 6 alkyl, (4) - OR 3, - SR 3, or - N(R 3) 2, and (5) - OC(O)R 3, - N(R 3)C(O)R 3, or - N(R 3)SO 2 R 3; wherein each R 3 is independently selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C 1 -C 6 alkyl, (3) substituted or unsubstituted C 2 -C 6 alkenyl, (4) substituted or unsubstituted C 2 -C 6 alkynyl, (5) substituted or unsubstituted C 3 -C 7 cycloalkyl, (6) substituted or unsubstituted C 5 -C 7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, (9) substituted or unsubstituted heterocyclyl, and (10) substituted or unsubstituted amino. 33. The composition of claim 32, further comprising at least one additional agent selected from the group consisting of irinotecan, topotecan, gemcitabine, imatinib, trastuzumab, 5-fluorouracil, leucovorin, carboplatin, cisplatin, taxanes, tezacitabine, cyclophosphamide, vinca alkaloids, geftinib, vatalanib, sunitinib, sorafenib, erlotinib, dexrazoxane, anthracyclines, and rituximab. 34. A method for treating a condition by modulating HSP90 activity comprising administering to a human or animal subject in need of such treatment an effective amount of a composition of claim 32. 35. The method of claim 34, wherein the condition is cancer."
  ],
  "description_excerpt": "The present invention relates to new 2-amino-quinazolin-5-one compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; to compositions containing 2-amino-quinazolin-5-one compounds and a pharmaceutical acceptable carrier; and to the uses of the compounds and compositions, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cell proliferative diseases.\n\nHeat shock or stress dramatically increases cellular production of several classes of highly conserved chaperone proteins, commonly known as heat-shock proteins (HSPs). These chaperones, including the members of the HSP60, HSP70 and HSP90 families, are ATP-dependent molecules that facilitate/ensure proper client protein (e.g. protein that requires interaction with the chaperones for its activity and stability) folding, prevent non-specific aggregations, and maintain active protein conformations.\n\nThe HSP90 family, comprised of HSP90 α and β, Grp94 and TRAP-1, is one of the most abundant cellular proteins, accounting for 1-2% of total proteins in a mammalian cell under normal conditions. HSP90 is unique among cellular chaperones in that it is not required for general co-translational protein folding, but instead is dedicated to a subset of signaling molecules that are frequently mutated or over-expressed in cancer cells. Many of these client proteins, including the mutated p53, Bcr-Abl, Raf-1, Akt, ErbB2, and steroid receptors etc, are well-known and established cancer drug targets.",
  "cpc": [
    "C07D 401/14",
    "A61P 35/00",
    "A61P 43/00",
    "C07D 239/84",
    "C07D 239/94",
    "C07D 401/04",
    "C07D 401/10",
    "C07D 401/12",
    "C07D 403/04",
    "C07D 403/10",
    "C07D 403/12",
    "C07D 409/10",
    "C07D 413/10",
    "C07D 417/10",
    "C07D 417/12",
    "C07D 417/14"
  ],
  "ipc": [
    "A61K 31/517",
    "A61K 31/5377",
    "C07D 403/02",
    "C07D 413/02"
  ],
  "inventors": [
    "Cornelia Bellamacina",
    "Abran Costales",
    "Brandon Doughan",
    "Susan Fong",
    "Zhenhai Gao",
    "Thomas Hendrickson",
    "Barry Levine",
    "Xiaodong Lin",
    "Timothy Machajewski",
    "Christopher McBride",
    "William Antonios-McCrea",
    "Maureen McKenna",
    "Kris Mendenhall",
    "Alice Rico",
    "Cynthia Shafer",
    "X. Wang",
    "Yi Xia",
    "Yasheen Zhou"
  ],
  "filing_date": "2006-04-14",
  "publication_date": "2007-02-01",
  "priority_date": "2005-04-14",
  "application_number": "US-40437206-A",
  "family_id": "37110373",
  "cited_by_count": 9
}