Compounds
First Claim
Patent Images
1. A compound of formula (I):
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wherein;
R is —
C(O)Ar1, —
C(R4)(R5)Ar1, or Ar2;
Ar1 is naphthyl, quinolyl, isoquinolyl, indolyl, benzofuranyl or benzothienyl, each of which can be optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, halogen or trifluoromethyl, or Ar1 is phenyl optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, halogen, trifluoromethyl, amino, nitro, cyano, trifluoromethoxy, phenoxy, —
CH2N(R6)2, —
NHSO2CF3, C1-4alkylsulphonylamino, —
NHC(O)R6a, CO2R7 or —
C(O)NR8R8a;
R4 represents H or C1-4 alkyl;
R5 represents H or OH;
each R6 independently represents H or C1-4 alkyl;
R6a represents H, C1-6 alkyl, aryl or arC1-4alkyl, wherein the aryl group or aryl moiety in the aralkyl group is phenyl or pyridyl, each of which may be optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, C1-4 alkylcarbonylamino, halogen or trifluoromethyl;
R7 represents H or C1-4 alkyl;
R8 and R8a each independently represent H, C1-4 alkyl, phenyl or pyridyl;
Ar2 is acenaphthenyl, indanyl, iminodihydrobenzofuranyl or fluorenyl, each of which can be optionally substituted by one or more substituents selected from OH, C1-4 alkyl, C1-4 alkoxy, halogen, or trifluoromethyl;
R1 and R2 are independently H, C1-6 alkyl, C3-6 alkenyl, CH2C3-5 cycloalkyl or C3-6 cycloalkyl;
R3 represents H, X—
R9 or X—
Ar3;
X represents S(O)n, C(O)NR10, C(O)O, NH(CO)NR10, NH(CO)O or SO2NR10;
n is 0, 1 or 2;
R9 represents a methyl group optionally substituted by one or more substituents selected from CN, CO2H, C1-5 alkoxycarbonyl, 5-tetrazolyl, SO2NH2 or C(O)NR11R12, or R9 represents C2-6 alkyl or C3-6 alkenyl, each of which may be optionally substituted by one or more substituents selected from OH, CN, CO2H, C1-5 alkoxy, C1-5 alkoxycarbonyl, 5-tetrazolyl, azide, phthalimido, SO2NH2, C(O)NR11R12, NR13R14, NHC(O)R15 or NHSO2R16 where R11, R12, R13 and R14 each independently represent H or C1-4 alkyl, R15 represents C1-4 alkyl, C1-4 alkoxy, di(C1-4alkyl)amino, or alkoxyalkylene containing up to 6 carbon atoms, and R16 represents C1-4 alkyl or trifluoromethyl;
or, additionally, in the case where X represents C(O)NR10, NH(CO)NR10 or SO2NR10, R9 and R10 together with the nitrogen atom to which they are attached may form a 4- to 7-membered heterocyclic ring which may be optionally substituted by one or more OH groups;
R10 represents H, C1-6 alkyl or is linked to R9 as defined above; and
Ar3 is phenyl, pyridyl or pyridine N-oxide, each of which may be optionally substituted by one or more substituents selected from OH, NO2, NH2, NHSO2CF3, C1-4 alkoxy, bis-C1-4alkanesulphonylamino, C1-4alkylcarbonylamino or C1-4alkoxycarbonylamino;
or a pharmaceutically-acceptable salt or solvate thereof.
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Abstract
The invention provides pharmaceutically useful thieno[2,3-d]pyrimidinediones, processes for their production, pharmaceutical compositions containing them and methods of treatment involving their use.
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Citations
16 Claims
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1. A compound of formula (I):
-
wherein; R is —
C(O)Ar1, —
C(R4)(R5)Ar1, or Ar2;
Ar1 is naphthyl, quinolyl, isoquinolyl, indolyl, benzofuranyl or benzothienyl, each of which can be optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, halogen or trifluoromethyl, or Ar1 is phenyl optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, halogen, trifluoromethyl, amino, nitro, cyano, trifluoromethoxy, phenoxy, —
CH2N(R6)2, —
NHSO2CF3, C1-4alkylsulphonylamino, —
NHC(O)R6a, CO2R7 or —
C(O)NR8R8a;
R4 represents H or C1-4 alkyl;
R5 represents H or OH;
each R6 independently represents H or C1-4 alkyl;
R6a represents H, C1-6 alkyl, aryl or arC1-4alkyl, wherein the aryl group or aryl moiety in the aralkyl group is phenyl or pyridyl, each of which may be optionally substituted by one or more substituents selected from C1-4 alkyl, C1-4 alkoxy, C1-4 alkylcarbonylamino, halogen or trifluoromethyl;
R7 represents H or C1-4 alkyl;
R8 and R8a each independently represent H, C1-4 alkyl, phenyl or pyridyl;
Ar2 is acenaphthenyl, indanyl, iminodihydrobenzofuranyl or fluorenyl, each of which can be optionally substituted by one or more substituents selected from OH, C1-4 alkyl, C1-4 alkoxy, halogen, or trifluoromethyl;
R1 and R2 are independently H, C1-6 alkyl, C3-6 alkenyl, CH2C3-5 cycloalkyl or C3-6 cycloalkyl;
R3 represents H, X—
R9 or X—
Ar3;
X represents S(O)n, C(O)NR10, C(O)O, NH(CO)NR10, NH(CO)O or SO2NR10;
n is 0, 1 or 2;
R9 represents a methyl group optionally substituted by one or more substituents selected from CN, CO2H, C1-5 alkoxycarbonyl, 5-tetrazolyl, SO2NH2 or C(O)NR11R12, or R9 represents C2-6 alkyl or C3-6 alkenyl, each of which may be optionally substituted by one or more substituents selected from OH, CN, CO2H, C1-5 alkoxy, C1-5 alkoxycarbonyl, 5-tetrazolyl, azide, phthalimido, SO2NH2, C(O)NR11R12, NR13R14, NHC(O)R15 or NHSO2R16 where R11, R12, R13 and R14 each independently represent H or C1-4 alkyl, R15 represents C1-4 alkyl, C1-4 alkoxy, di(C1-4alkyl)amino, or alkoxyalkylene containing up to 6 carbon atoms, and R16 represents C1-4 alkyl or trifluoromethyl;
or, additionally, in the case where X represents C(O)NR10, NH(CO)NR10 or SO2NR10, R9 and R10 together with the nitrogen atom to which they are attached may form a 4- to 7-membered heterocyclic ring which may be optionally substituted by one or more OH groups;
R10 represents H, C1-6 alkyl or is linked to R9 as defined above; and
Ar3 is phenyl, pyridyl or pyridine N-oxide, each of which may be optionally substituted by one or more substituents selected from OH, NO2, NH2, NHSO2CF3, C1-4 alkoxy, bis-C1-4alkanesulphonylamino, C1-4alkylcarbonylamino or C1-4alkoxycarbonylamino;
or a pharmaceutically-acceptable salt or solvate thereof.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
6-(4-Methoxyphenylmethyl)-3-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-(4-Methoxyphenylmethyl)-3-methyl-1-(2-methyl-2-propenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1-(2-Methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-5-[(2-pyridinyl)thio]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 5-[(3-Hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, Methyl 4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]butanoate, 4-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]butanoic acid, Methyl 4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)sulfinyl]butanoate, Methyl 4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)sulfonyl]butanoate, 4-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)sulfonyl]butanoic acid, 6-Benzyl-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 3-Methyl-1-(1-methylethyl)-6-(phenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-[(1-Hydroxy-1-phenyl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, (±
)5-[(2-Hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,1,2,3,4-Tetrahydro-N-(2-hydroxyethyl)-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide, (3R)-1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbonyl}pyrrolidin-3-ol, 1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbonyl}piperidin-4-ol, (3R)-1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbonyl}piperidin-3-ol, 1,2,3,4-Tetrahydro-N-(2-hydroxyethyl)-3,N-dimethyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide, 2-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carboxamido}acetic acid, 3-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carboxamido}propanoic acid, 2-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carboxamido}acetamide, 1-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbonyl}pyrrolidine, 1,2,3,4-Tetrahydro-N-(2-hydroxyethyl)-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-sulfonamide, 5-[(3-Methoxyphenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione, 5-[(3-Hydroxyphenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione, 5-[(3-Hydroxyphenyl)sulfinyl]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione, 5-[(3-Hydroxyphenyl)sulfonyl]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-5-[(3-nitrophenyl)thio]thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 5-[(3-Aminophenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 5-{[3-{(Bis-methanesulfonyl)amino}phenyl]thio}-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 5-[(3-Methoxycarbonylaminophenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 5-[(3-Acetamidophenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-5-[(4-nitrophenyl)thio]thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 5-[(4-Aminophenyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-5-[(5-nitropyridin-2-yl)thio]thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 2-{[1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]thio}pyridine N-oxide, 5-[(3-Azidopropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno-[2,3-d]pyrimidine-2,4(1H,3H)-dione, 5-[(3-Aminopropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno [2,3-d]pyrimidin-5-yl)thio]propyl}acetamide, N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]propyl}-N′
,N′
-dimethylurea,N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]propyl}-methoxyacetamide, Methyl N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]propyl}carbamate, N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]propyl}methanesulfonamide, N-{3-[(1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)thio]propyl}trifluoromethanesulfonamide, 5-{[3-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)propyl]thio}-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, N-(2-Hydroxyethyl)-N′
-[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]urea,2-Hydroxyethyl [1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbamate, N-(2-Hydroxyethyl)-N-methyl-N′
-[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]urea,6-[(1-Hydroxy-1-(3-fluorophenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno-[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 6-[(3-Fluorophenyl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-(1H, 3H)-dione, 6-[(1-Hydroxy-1-(2-bromophenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-(2-methylphenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-(3-cyanophenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-(3-trifluoromethylphenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-(3-phenyloxyphenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-(1-naphthalenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-[(1-Hydroxy-1-(6-quinolinyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-[(1 -Hydroxy-1-(4-quinolinyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, (±
)6-[1-(Benzo[b]furan-2-yl)-1-hydroxymethyl]-3-methyl-1-(2-methylpropyl))thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,6-[(1-Hydroxy-1-(2-chloro-6-fluorophenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno-[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-phenyl)ethyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-[(1-Hydroxy-1-(4-trifluoromethylphenyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, (±
)6-(2,3-dihydro-1-hydroxy-1H-indenyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,6-[(1-Hydroxy-1-(2-quinolinyl))methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-(1-Hydroxy-1-[3-quinolinyl]methyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-(2-bromophenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-(2-methylphenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-(3-cyanophenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-(3-trifluoromethylphenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-(3-phenyloxyphenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(4-quinolinylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(6-quinolinylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 3-Methyl-1-(2-methylpropyl)-6-(2-quinolinylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, trifluoroacetic acid salt, 6-(2-Benzo[b]furanylmethyl)-3-methyl-1-(2-methylpropyl)-)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 6-(2-Chloro-6-fluorophenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-(1-Phenylethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 6-(4-Trifluoromethylphenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, (±
)6-(2,3-dihydro-1H-inden-1-yl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,6-(3-Imino-1,3-dihydro-benzo[c]furan-1-yl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 2-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl)methyl]benzamide, (±
)6-(1-Hydroxy-1-[1-naphthalenyl]methyl)-5-([3-hydroxypropyl]thio)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,3-Methyl-1-(2-methylpropyl)-6-(1-naphthalenylcarbonyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, (±
)-5-[(3-Hydroxybutyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,6-(3-Fluorophenyl)methyl-5-[(3-hydroxypropyl)thio]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 5-[(5-Amino-2-pyridinyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, Ethyl 1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-phenylmethyl-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate, 1,2,3,4-Tetrahydro-3,N,N-trimethyl-1-(2-methylpropyl)-6-phenylmethyl-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide, 6-[1-Hydroxy-(4-nitrophenyl)methyl]-3-methyl-1-(2-methylpropyl)thieno-[2,3-d]pyrimidin-2,4(1H, 3H)-dione, 6-(4-Nitrophenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidin-2,4(1H, 3H)-dione, 6-(4-Aminophenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione, 4-(3,4-Dimethoxyphenyl)-N-{4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl)methyl]phenyl}-butanamide, and 3-Acetamido-N-(4-[1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl)methyl]phenyl)benzamide.
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13. A process for the preparation of a compound of formula (I) as defined in claim 1 which comprises:
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(a) preparation of a compound of formula (I) wherein X is SO or SO2, by oxidation of a compound of formula (I) wherein X is S(O)n and n is 0 or 1;
or(b) preparation of a compound of formula (I) wherein X is S, by reacting a compound of general formula
wherein R, R1 and R2 are as defined in claim 1, with a compound of general formula (III), R17—
S—
S—
R17, wherein the groups R17 both represent R9 or Ar3 as defined in claim 1, or with a compound of general formula (IV), L—
S—
R17, wherein L represents a leaving group and R17 is as defined above;
or(c) preparation of a compound of formula (I) wherein R3 represents H, by reaction of a compound of general formula
wherein R18 and R19 each independently represent an alkyl or aryl group and R and R1 are as defined in claim 1, with a compound of general formula (VI), R2NH2, wherein R2 is as defined in claim 1;
or(d) preparation of a compound of formula (I) wherein X is C(═
O)NR10, by reacting a compound of general formula
wherein R, R1 and R2 are as defined in claim 1, with a compound of general formula
wherein R9 and R10 are as defined in claim 1;
or(e) preparation of a compound of formula (I) wherein X is NH(CO)NR10, by reacting a compound of general formula
wherein R, R1 and R2 are as defined in claim 1, with a compound of formula (VIII) as hereinbefore defined;
or(f) preparation of a compound of formula (I) wherein X is NH(CO)O, by reacting a compound of formula (IX) as defined above, with a compound of general formula (X), R9OH, wherein R9 is as defined in claim 1;
or(g) preparation of a compound of formula (I) wherein X is SO2NR10, by reacting a compound of general formula
wherein L1 represents a leaving group and R, R1 and R2 are as defined in claim 1, with a compound of formula (VIII) as defined above;
or(h) preparation of a compound of formula (I) wherein X is C(O)O, by reacting a compound of general formula
wherein R3 represents CO2R9 or CO2Ar3 and R, R1, R18 and R19 are as hereinbefore defined, with a compound of general formula (VI) as hereinbefore defined;
and optionally after (a), (b), (c), (d), (e), (f), (g) or (h) converting the compound of formula (I) obtained to a further compound of formula (I) and/or forming a pharmaceutically-acceptable salt or solvate thereof.
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14. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically-acceptable salt or solvate thereof, according to claim 1 in association with a pharmaceutically-acceptable adjuvant, diluent or carrier.
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15. A process for the preparation of a pharmaceutical composition as claimed in claim 14 which comprises mixing a compound of formula (I), or a pharmaceutically-acceptable salt or solvate thereof, according to as defined above with a pharmaceutically-acceptable adjuvant, diluent or carrier.
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16. A method of treating allograft rejection which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I), or a pharmaceutically-acceptable salt or solvate thereof, as claimed in claim 1.
Specification