Pyrido(3,2-d)pyrimidines useful for treating viral infections
First Claim
Patent Images
1. A pyrido(3,2-d)pyrimidine derivative represented by the structural formula (I):
1 Assignment
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Accused Products
Abstract
Pyrido(3,2-d)pyrimidine derivatives represented by the structural formula (I):
wherein:
- R4 is hydrogen, and
- R1, R2 and R3 together provide a specific substitution pattern,
pharmaceutical acceptable addition salts, stereochemical isomeric forms, N-oxides, solvates and pro-drugs thereof, are useful in the treatment of hepatitis C.
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Citations
17 Claims
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1. A pyrido(3,2-d)pyrimidine derivative represented by the structural formula (I):
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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2. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein
R2 is XR7 or is selected from the group consisting of N-morpholinyl, N-thiomorpholinyl, N-thiomorpholinyl dioxide, cyclopropyl, N-piperidinyl and N-pyrrolidinyl, wherein said N-pyrrolidinyl is optionally substituted with C1-4 alkylsulfonyl; -
X is selected from the group consisting of O, S, NR13 and CH2; and R7 is selected from the group consisting of C1-20 alkyl, C3-10 cycloalkyl, aryl, and aryl-C1-4 alkyl; wherein said C1-20 alkyl is substituted with one or more substituents independently selected from the group consisting of methylsulfonyl, carbamoyl, halogen and C1-4 alkoxy when X is NR13, or said C1-20 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of C1-4 alkoxy, and halo-C1-4 alkoxy when X is O; wherein said C3-10 cycloalkyl is substituted with one or more substituents independently selected from the group consisting of C1-20 alkyl and cyano when X is O, S, CH2 or NR13; wherein said aryl is optionally substituted with one or more halogen when X is O, S or CH2; or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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3. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein:
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R1 is selected from the group consisting of —
NH—
CHR5R6 and —
NH—
R8,R5 and R6 are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl and heterocyclyl selected from imidazol-2-yl and thien-2-yl, with the proviso that both R5 and R6 are not hydrogen, and wherein said aryl is substituted with one or more substituents selected from the group consisting of cyano, trifluoromethoxy, C1-4 alkyl, C1-4 alkoxy, di-C1-4 alkylamino, mono-C1-4 alkylamino, —
SO2NHR13, —
CON(R13)2, —
NR12COR10, —
SO2R13, —
NHSO2R13, and phenoxy, wherein said C1-4 alkyl is optionally substituted with —
SO2NHR13, andsaid aryl is optionally further substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, nitro and trifluoromethyl; wherein said C1-6 alkyl is substituted with one or more substituents selected from the group consisting of halogen, C1-4 alkoxy, aryl, —
P(O)(OR13)2, carbamoyl, and —
SO2NHR13; andR8 is selected from the group consisting of C3-10 cycloalkyl substituted at the carbon position adjacent to the N atom of —
NHR8 with arylwherein said aryl is optionally substituted with halogen;
phenyl; and
4-fluorophenyl,or a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof or a N-oxide thereof.
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4. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein:
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R3 is mono-substituted or disubstituted aryl, wherein at least one substituent of said aryl is independently selected from the group consisting of C1-6 alkyl, —
CONHR9, —
NR12COR10, —
NR12SO2R11, and —
SO2NHR14,wherein said C1-6 alkyl is substituted with one or more hydroxy and optionally further substituted with one or more halogen; and wherein a further substituent of said aryl is independently selected from the group consisting of halogen, amino, C1-4 alkylamino, hydroxy, cyano, C1-6 alkyl, C1-6 alkoxy, —
CONNR9, —
NR12COR10, —
NR12SO2R11, —
SO2NH2, and —
SO2NHR14,wherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and hydroxy; and each R10 is independently selected from the group consisting of C1-6 alkyl;
C1-6 alkoxy;
C3-10 cycloalkyl and amino,wherein said C1-6 alkyl is substituted with one or more substituents independently selected from the group consisting of amino, cyano, halogen, and hydroxy; wherein said C1-6 alkoxy is substituted with one or more substituents independently selected from the group consisting of amino, C1-4 alkylamino, cyano, di-C1-4 alkylamino, and halogen; wherein said C3-10 cycloalkyl is substituted with one or more substituents independently selected from the group consisting of cyano, amino, and hydroxy; and wherein said amino is optionally substituted with one or more substituents independently selected from the group consisting of C3-10 cycloalkyl and C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of amino, C1-4 alkylamino, cyano, di-C1-4 alkylamino, and halogen or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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5. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein
R2 is XR7; -
X is selected from the group consisting of O, S, and NR13 wherein R13 is H; and R7 is selected from the group consisting of C2-20 alkyl, C3-10 cycloalkyl, and aryl C1-4 alkyl that is benzyl when X is NR13; and R7 is C1-4 alkyl when X is O or S; or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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6. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein R2 is selected from the group consisting of ethoxy, isopropylamino, 2,2,2-trifluoroethylamino, 2,2-difluoroethylamino, methanesulfonylethylamino, cyclo-propylamino and cyclopropyl, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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7. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein R3 is a mono-substituted or disubstituted aryl that is a phenyl group, wherein at least one substituent of said phenyl group is located in para position with respect to the carbon atom to which R3 is bound, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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8. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein R3 is a mono-substituted or disubstituted aryl that is a phenyl group, wherein at least one substituent of said phenyl group is located in meta position with respect to the carbon atom to which R3 is bound, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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9. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein R3 is selected from the group consisting of phenyl, 4-fluorophenyl, 4-methylphenyl, 3-chloro-4-ethoxyphenyl, 3-ethoxy-4-fluorophenyl, 3-methyl-4-fluorophenyl, 3,4-dichlorophenyl and 3,4-methylenedioxy-phenyl, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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10. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein
R5 is hydrogen and R6 is selected from the group consisting of C3-10 cycloalkyl, heterocyclyl selected from imidazol-2-yl and thien-2-yl, and phenyl, wherein said phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, trifluoromethyl, trifluoromethoxy, C1-4 alkyl, C1-4 alkoxy, dimethylamino, diethylamino and phenoxy, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof. -
11. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein R1 is selected from the group consisting of 4-fluorobenzylamino, 2,2,2-trifluoroethylamino and 4-sulfamoylbenzylamino, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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12. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein
R5 is hydrogen and R6 is selected from the group consisting of C1-6 alkyl that is trifluoromethyl, aryl that is naphthyl, imidazol-2-yl and thien-2-yl, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof. -
13. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein R8 is selected from the group consisting of phenyl, pyridazinyl and pyrazolyl and wherein said R8 is optionally substituted with a substituent selected from the group consisting of halogen and methyl, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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14. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein:
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R1 is selected from the group consisting of 2,2,2-trifluoroethylamino, 4-fluorobenzylamino, 3,4-difluorobenzylamino, 2,6-difluoro-4-methoxybenzyl-amino, 4-chloro-2,6-difluorobenzylamino, 4-chloro-2-fluorobenzylamino, 2,4,6-trifluoro-benzylamino, 4-chloro-3-fluorobenzylamino, 2,4,4-trifluoro-benzylamino, 3-chloro-4-fluorobenzylamino, 2-chloro-4-fluorobenzylamino, 3-fluoro-4-trifluoromethyl-amino, 3,5-difluorobenzylamino, 3,4,5-trifluoro-benzylamino, 3-fluorobenzylamino, 3-chloro-2-fluorobenzylamino, 4 fluorophenylamino, phenylamino, 6-methyl-pyridazin-3-ylamino, pyridin-2-ylmethylamino, pyridin-3-ylmethylamino, 2-morpholin-4-ylethylamino, 2,2-difluoroethyl-amino, 2-methoxyethylamino, 4-sulfamoylbenzylamino, 1-(4 fluorophenyl)-cyclopropyl-amino, 2,4-difluorobenzylamino, 1-phenylethyl-amino, thiazol-2-ylmethylamino, oxazol-4-ylmethylamino, isoxazol-3-ylmethylamino, 4-(N-isopropylsulfamoylmethyl)benzylamino, phenethylamino, 4-methanesulfonyl-benzylamino, 4-pyrrolidin-1-yl-benzylamino, 4-(4-methylpiperazin-1-yl)benzylamino, (N,N-dimethylcarboxamido)-benzylamino, 4-[1,2,3]thiadiazol-4-ylbenzylamino, 2 fluoro-4-sulfamoylbenzylamino, 4-[1,3,4]-oxadiazol-2-ylmethylamino, thiazol-5-ylmethyl-amino 1-(4-sulfamoylphenyl)ethylamino, 4-([1,2,4](triazol-1-yl)benzylamino oxazol-2-ylmethylamino, 2-([1,2,4]-triazol-1-yl)ethylamino 1-(4-[1,2,4]triazol-1-yl-phenyl)-ethylamino, 2-(diethylphosphono)ethylamino, 2-sulfamoylethylamino, 2-carbamoylethylamino, 4-carbamoylbenzylamino, 4-(N,N-dimethylcarboxamido)-benzylamino, and 4-(N-methylmethanesulfonamido)-benzylamino; R2 is selected from the group consisting of tetrahydrofuran-3-yloxy, ethoxy, hydroxy, n-propionamido-amino, 2-methyl-2-hydroxy-propylamino, methoxy, 3-methanesulfonyl-pyrrolidin-1-yl, N-methanesulfonylethyl-N-methylamino, 1-isopropyl-piperidin-4-ylamino, ethylamino, pyridin-3-ylmethylamino, N-morpholin-4-ylethylamino, 2,2,2-trifluoroethylamino, 2-methoxyethylamino, isopropylamino, dimethylamino, diethylamino, cyclopentoxy, cyclobutoxy, propyl, methanesulfonylethylamino, 2,2-difluoroethylamino, cyclopropoxy, cyclopropyl-amino, 4-([1,2,4]triazol-1-yl)phenylamino, 3-fluorophenylamino, 2-methoxy-ethoxy, tetrahydro-furan-3-ylamino, oxetan-3-yloxy, 1-methylcyclopropoxy, 2-hydroxyethylamino, 1-cyano-cyclopropylamino, N-morpholinyl, N-thiomorpholinyl, N-thiomorpholinyl dioxide, cyclopropyl, N-piperidinyl and N-pyrrolidinyl, wherein said N-pyrrolidinyl is optionally substituted with C1-4 alkylsulfonyl; R3 is selected from the group consisting of optionally mono-substituted or disubstituted aryl, wherein each substituent of said aryl is independently selected from the group consisting of halogen, hydroxy, amino, C1-4 alkylamino, cyano, C1-6 alkyl, C1-6 alkoxy, —
CONHR9, —
NR12COR10, —
NR12SO2R11, —
SO2NH2, and —
SO2NHR14;wherein said C1-6 alkyl is optionally substituted with hydroxy; R9 is selected from the group consisting of hydrogen;
C3-10 cycloalkyl;
C1-6 alkyl;
C1-6 alkoxy; and
phenyl,wherein said C3-10 cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halogen, hydroxy, oxo, amino, C1-6 alkyl and C1-6 alkoxy; wherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of amino, alkylamino, cyano, di-C1-4 alkylamino, and halogen; and wherein said phenyl is optionally and independently substituted with one or more halogen; R10 and R11 are each independently selected from the group consisting of C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of amino, cyano, halogen, and hydroxy;
C1-6 alkoxy;
C3-10 cycloalkyl; and
aminowherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of amino, cyano, halogen, and hydroxy; wherein said C1-6 alkoxy is optionally substituted with one or more substituents independently selected from the group consisting of amino, C1-4 alkylamino, cyano, di-C1-4 alkylamino, and halogen; wherein said C3-10 cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of amino and hydroxy; wherein said amino is optionally substituted with one or more substituents independently selected from the group consisting of C3-10 cycloalkyl and C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of amino, C1-4 alkylamino, cyano, di-C1-4 alkylamino, and halogen; R12 is selected from the group consisting of hydrogen and C1-6 alkyl, wherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halogen and hydroxy; and R14 is C1-4 alkyl optionally substituted with one or more C1-4 alkoxy; or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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15. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein:
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R1 is selected from the group consisting of —
NH—
CHR5R6 and —
NH—
R8;R5 and R6 are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl and heterocyclyl selected from imidazol-2-yl and thien-2-yl, with the proviso that both R5 and R6 are not hydrogen, and wherein said aryl is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, trifluoromethyl, trifluoromethoxy, C1-4 alkyl optionally substituted with —
SO2NHR13, wherein R13 is C1-4 alkyl, C1-4 alkoxy, di-C1-4 alkylamino, mono-C1-4 alkylamino, —
SO2NHR13 wherein R13 is hydrogen, —
CON(R13)2 wherein R13 is hydrogen, —
SO2R13 wherein R13 is C1-4alkyl, —
NHSO2R13 wherein R13 is hydrogen, —
NHSO2R13 wherein R13 is C1-4 alkyl, and phenoxy;wherein said C1-6 alkyl is substituted with one or more substituents selected from the group consisting of halogen, C1-4 alkoxy, aryl, —
P(O)(OR13)2 wherein R13 is C1-6 alkyl, carbamoyl, —
SO2NHR13 wherein R13 is hydrogen and —
SO2NHR13 wherein R13 is C1-4 alkyl;R8 is selected from the group consisting of C3-10 cycloalkyl, heteroaryl selected from pyridazinyl and pyrazolyl and aryl wherein said heteroaryl or aryl is optionally substituted with one or more substituents selected from the group consisting of halogen and C1-4 alkyl and wherein said C3-10 cycloalkyl is optionally substituted at the carbon position adjacent to the N atom of —
NHR8 with aryl wherein said aryl is optionally substituted with halogen;R2 is selected from the group consisting of tetrahydrofuran-3-yloxy, ethoxy, hydroxy, n-propionamido-amino, 2-methyl-2-hydroxy-propylamino, methoxy, 3-methanesulfonyl-pyrrolidin-1-yl, N-methanesulfonylethyl-N-methylamino, 1-isopropyl-piperidin-4-ylamino, ethylamino, pyridin-3-ylmethylamino, N-morpholin-4-ylethylamino, 2,2,2-trifluoroethylamino, 2-methoxyethylamino, isopropylamino, dimethylamino, diethylamino, cyclopentoxy, cyclobutoxy, propyl, methanesulfonyl-ethylamino, 2,2-difluoroethylamino, cyclopropoxy, cyclopropylamino, 4-[1,2,4]triazol-1-yl-anilino, 3-fluoroanilino, 2-methoxy-ethoxy, tetrahydrofuran-3-ylamino, oxetan-3-yloxy, 1-methylcyclopropoxy, 2-hydroxy-ethylamino, 1-cyano-cyclopropylamino, N-morpholinyl, N-thiomorpholinyl, N-thiomorpholinyl dioxide, cyclopropyl, N-piperidinyl and N-pyrrolidinyl, wherein said N-pyrrolidinyl is optionally substituted with C1-4 alkylsulfonyl; and R3 is selected from the group consisting of optionally mono-substituted or disubstituted aryl, wherein each substituent of said aryl is independently selected from the group consisting of halogen, hydroxy amino, C1-4 alkylamino, cyano, C1-6 alkyl, C1-6 alkoxy, —
CONHR9, —
NR12COR10, —
NR12SO2R11, —
SO2NH2, and —
SO2NHR14; andwherein said C1-6 alkyl is optionally substituted with hydroxyl; R9 is selected from the group consisting of hydrogen, C3-10 cycloalkyl;
C1-6 alkyl;
C1-6 alkoxy; and
phenylwherein said C3-10 cycloalkyl is optionally substituted with one more substituents independently selected from the group consisting of cyano, halogen, hydroxy, oxo, amino, C1-6 alkyl and C1-6 alkoxy; wherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of amino, alkylamino, cyano, dialkylamino, and halogen;
C1-6 alkoxy; andwherein said phenyl is optionally and independently substituted with one or more halogen; R10 and R11 are each independently selected from the group consisting of C1-6 alkyl;
C1-6 alkoxy;
C3-10 cycloalkyl; and
aminowherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of amino, cyano, halogen, and hydroxy; wherein said C1-6 alkoxy is optionally substituted with one or more substituents independently selected from the group consisting of amino, C1-4 alkylamino, cyano, di-C1-4 alkylamino, and halogen; wherein said C3-10 cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of amino and hydroxy; and wherein said amino is optionally substituted with one or more substituents independently selected from the group consisting of C3-10 cycloalkyl and C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of amino, C1-4 alkylamino, cyano, di-C1-4 alkylamino, and halogen; R12 is selected from the group consisting of hydrogen and C1-6 alkyl, wherein said C1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halogen and hydroxy; and R14 is C1-4 alkyl optionally substituted with one or more substituents independently selected from the group consisting of C1-4 alkoxy; or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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16. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein:
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R1 is selected from the group consisting of —
NH—
CHR5R6 and —
NH—
R8;R5 and R6 are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-10 cycloalkyl, aryl and heterocyclyl selected from imidazol-2-yl and thien-2-yl, with the proviso that both R5 and R6 are not hydrogen, and wherein said aryl is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, nitro, cyano, trifluoromethyl, trifluoromethoxy, C1-4 alkyl optionally substituted with —
SO2NHR13, wherein R13 is C1-4 alkyl, C1-4 alkoxy, di-C1-4 alkylamino, mono-C1-4 alkylamino, —
SO2NHR13 wherein R13 is hydrogen, —
CO2NHR13 wherein R13 is hydrogen, —
SO2R13 wherein R13 is C1-4 alkyl, —
NHSO2R13 wherein R13 is hydrogen, —
NHSO2R13 wherein R13 is C1-4 alkyl, and phenoxy;wherein said C1-6 alkyl is substituted with one or more substituents selected from the group consisting of halogen, C1-4 alkoxy, aryl, —
P(O)(OR13)2 wherein R13 is C1-6 alkyl, carbamoyl, —
SO2NHR13 wherein R13 is hydrogen and —
SO2NHR13 wherein R13 is C1-4 alkyl;R8 is selected from the group consisting of C3-10 cycloalkyl, heteroaryl selected from pyridazinyl and pyrazolyl and aryl wherein said heteroaryl or aryl is optionally substituted with one or more substituents selected from the group consisting of halogen and C1-4 alkyl and wherein said C3-10 cycloalkyl is optionally substituted at the carbon position adjacent to the N atom of —
NHR8 with aryl wherein said aryl is optionally substituted with halogen;R2 is selected from the group consisting of tetrahydrofuran-3-yloxy, ethoxy, hydroxy, 2 carbamoylethylamino, 2-methyl-2-hydroxy-propylamino, methoxy, 3-methanesulfonyl-pyrrolidin-1-yl, N-methanesulfonylethyl-N-methylamino, 1-isopropylpiperidin-4-ylamino, ethylamino, pyridin-3-ylmethylamino, N-morpholin-4-ylethylamino, 2,2,2-trifluoroethylamino, 2-methoxyethylamino, isopropylamino, dimethylamino, diethylamino, cyclopentoxy, cyclobutoxy, propyl, methane-sulfonylethylamino, 2,2-difluoroethylamino, cyclopropoxy, cyclopropylamino, 4-[1,2,4]triazol-1-yl-anilino, 3-fluoroanilino, 2-methoxy-ethoxy, tetrahydrofuran-3-ylamino, oxetan-3-yloxy, 1-methylcyclopropoxy, 2-hydroxyethylamino, 1-cyano-cyclopropylamino, N-morpholinyl, N-thiomorpholinyl, N-thiomorpholinyl dioxide, cyclopropyl, N-piperidinyl and N-pyrrolidinyl, wherein said N-pyrrolidinyl is optionally substituted with C1-4 alkylsulfonyl; and R3 is selected from the group consisting of 4-fluorophenyl, 5-amino-pyrazin-2-yl, 4-(N-(2-dimethylaminoethyl)carbamoyl)phenyl, 3-chloro-4-fluorophenyl, 4-(N-cyclopropylcarbamoyl)phenyl, 3-(N-methylsulfonyl-amino)phenyl, 4-(cyclopropanecarboxamido)phenyl, 3-sulfamoyl-4-fluorophenyl, 4-(2-hydroxy-acetamido)-phenyl, 4-(2-amino-acetamido)phenyl, 4-[3-(2-morpholin-4-yl-ethyl)-ureido]phenyl, 4-(morpholine-4-carboxamido)phenyl, 4-(pyrrolidine-1-carboxamido)phenyl, 4-(3-cyclopropylureido)phenyl, 4-ureidophenyl, 4-[(4-hydroxy-2-oxo-pyrrolidin-1-yl)]phenyl, 1H-indazol-5-yl, 2-oxo-indol-5-yl, 2-cyclopropanecarboxamido-pyrimidin-5-yl, 3-(2-pyrrolidin-1-yl-ethanesulfonamido)phenyl, 3-(cyclopropanesulfonamido)-phenyl, 4-sulfamoylphenyl, 3-(dimethylaminesulfonamido)phenyl 3-sulfamoylphenyl, 4-(3-hydroxy-2-oxo-pyrrolidin-1-yl)phenyl, 2-fluoropyridin-5-yl, 4-(4-hydroxypyrrolidin-2-carboxamido)phenyl, 4-(pyrrolidin-2-carboxamido)phenyl, 4-(pyrrolidin-3-carboxamido)-3-fluoro-phenyl, 4-(pyrrolidin-3-carboxamido)phenyl, 4-(2-(pyrrolidin-1-yl)-ethoxycarbonyl-amino)-phenyl, 3-(4-(tert-butoxycarbonylamino)-piperidin-1-sulfonyl)-4-chloro-phenyl, 3-(N-(1 (tert-butoxycarbonyl)-pyrrolidin-3-yl)-sulfamoyl)-4-fluoro-phenyl, 4-(methoxycarbonylamino)-phenyl, 3-(N-(1-(tert-butoxycarbonyl)-piperidin-4-yl)-sulfamoyl)-4-chloro-phenyl, 3-(N-(1-(tert-butoxycarbonyl)-piperidin-4-yl)-sulfamoyl)-4-fluoro-phenyl, 4-[3-(2 pyrrolidin-1-yl-ethyl)ureido]phenyl, 4-(N-(2-hydroxy-1,1-dimethyl-ethyl)-carbamoyl)phenyl 4-(N-(2-(pyrrolidin-1-yl)-1,1-dimethyl-ethyl)carbamoyl)phenyl, 2-amino-thiazol-5-yl, 5-hydroxymethylfuran-2-yl, 4-(N-pyrrolidin-2-one)-phenyl, 4-carbamoyl-phenyl, 4-(N-1 cyano-1-cyclopropyl-carbamoyl)-phenyl, 4-(N-1 amino-1-cyclopropylcarbamoyl)-phenyl, 4-(N-1-hydroxy-1-cyclopropylcarboxamido)-phenyl, 3-(N-(2-hydroxyethyl)methylsulfonamido)-phenyl, 4-(N-(2-(morpholin-4-yl)-1,1-dimethyl-ethyl)carbamoyl)phenyl, 4-(2-oxo-pyrrolidin-1-yl)phenyl, 4-(2-amino-2-methylpropionamido)phenyl, 4-(N-cyclopropylcarbamoyl)phenyl, 4-(3-hydroxy-2-aminopropionamido)phenyl, 3-cyclopropanesulfonamido-4-fluoro-phenyl, 4-(2-amino-propionamido)-phenyl, 4-(3-hydroxy-2-amino-butyramido)phenyl, 3,5-dimethyl-isoxazol-4-yl, 1-methyl-1H-pyrazol-4-yl, 5-pyrrolidin-1-ylpyrazin-2-yl, 2-trifluoromethylpyridin-4-yl, 2-aminopyridin-4-yl, 4-hydroxyphenyl, 2-pyrrolidin-1-yl-thiazol-4-yl, 2-methoxypyridin-4-yl, 2-cyanopyridin-4-yl, 2-aminopyrimidin-5-yl, 3-cyanophenyl, 4-(1-methylpyrrolidine-3-carboxamido)-3-fluorophenyl, 4-(1-methylpyrrolidine-3-carboxamido)-phenyl, 3-cyclopropanesulfonamido-4-fluoro-phenyl, 1H-pyrazol-4-yl, 3-(N (1 isopropyl-piperidin-4-yl)sulfamoyl)-4-chlorophenyl, 3-(N-(2-pyrrolidin-1-yl-ethyl)sulfamoyl)-4-chlorophenyl, 3-(4-isopropyl-piperazin-1-sulfonyl)-4-chloro-phenyl 3-(N-pyrrolidin-3-yl-sulfamoyl)-4-chlorophenyl, 3-(N-(2-methoxyethyl)sulfamoyl)-4-chlorophenyl, 3-(N-piperidin-4-ylsulfamoyl)-4-chlorophenyl, pyridazin-4-yl, 4-cyanophenyl, 4-fluoro-3-(piperazin-1-sulfonyl)-phenyl, 4-fluoro-3-(4-tert-butoxycarbonyl-piperazin-1-sulfonyl)-phenyl, 4-isopropylamino-pyrazol-1-yl, [1,2,4]triazol-1-yl, imidazol-1-yl, imidazol-2-yl, 6-oxo-1,6-dihydro-pyridin-3-yl, 2-oxo-1,2-dihydro-pyridin-4-yl, 3-hydroxy-2-oxo-pyrrolidin-1-yl, and 4-chlorophenyl, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof.
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17. A pharmaceutical composition comprising:
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one or more pharmaceutically acceptable carriers, a pyrido(3,2-d)pyrimidine derivative according to claim 1, or a pharmaceutically acceptable addition salt or a stereochemical isomeric form thereof or a N-oxide thereof, and optionally one or more antiviral agents.
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2. A pyrido(3,2-d)pyrimidine derivative according to claim 1, wherein
Specification
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Current AssigneeGilead Sciences Inc.
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Original AssigneeGilead Sciences Inc.
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InventorsBondy, Steven S., Chou, Chien-hung, Watkins, William John, Chong, Lee S., Zhang, Jennifer R., Mishra, Ruchika
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Primary Examiner(s)Bernhardt, Emily
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Assistant Examiner(s)Jaisle, Cecilia M
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Application NumberUS11/963,723Publication NumberTime in Patent Office2,342 DaysField of Search544/279, 514/264.11US Class Current514/264.11CPC Class CodesA61P 31/12 AntiviralsA61P 31/14 for RNA virusesC07D 471/04 Ortho-condensed systems