CA2339664A1 - Thieno{2,3,-d}pyrimidinedione derivatives and their use as immunosuppressants - Google Patents
Thieno{2,3,-d}pyrimidinedione derivatives and their use as immunosuppressants Download PDFInfo
- Publication number
- CA2339664A1 CA2339664A1 CA002339664A CA2339664A CA2339664A1 CA 2339664 A1 CA2339664 A1 CA 2339664A1 CA 002339664 A CA002339664 A CA 002339664A CA 2339664 A CA2339664 A CA 2339664A CA 2339664 A1 CA2339664 A1 CA 2339664A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- dione
- pyrimidine
- methylpropyl
- thieno
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229960003444 immunosuppressant agent Drugs 0.000 title 1
- 239000003018 immunosuppressive agent Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 48
- JGOOQALRLGHKIY-UHFFFAOYSA-N 1h-thieno[2,3-d]pyrimidine-2,4-dione Chemical class O=C1NC(=O)NC2=C1C=CS2 JGOOQALRLGHKIY-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 228
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 91
- -1 amino, nitro, cyano, trifluoromethoxy, phenoxy Chemical group 0.000 claims description 69
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 61
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 29
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 12
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229910052717 sulfur Chemical group 0.000 claims description 5
- JCNVVNANFIZEMZ-UHFFFAOYSA-N 6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3)=O)C(C)C)=NC2=C1 JCNVVNANFIZEMZ-UHFFFAOYSA-N 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
- 208000027771 Obstructive airways disease Diseases 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 230000001506 immunosuppresive effect Effects 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 235000010269 sulphur dioxide Nutrition 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- AMUJWWSZSRTUKN-UHFFFAOYSA-N 5-(3-hydroxypropoxy)-3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound OCCCOC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 AMUJWWSZSRTUKN-UHFFFAOYSA-N 0.000 claims description 3
- ARZUNQNWVZXAOQ-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=NC2=CC=CC=C2N1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O ARZUNQNWVZXAOQ-UHFFFAOYSA-N 0.000 claims description 3
- 206010062016 Immunosuppression Diseases 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 230000002441 reversible effect Effects 0.000 claims description 3
- 239000004291 sulphur dioxide Substances 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- IJOFJRNWCALZKL-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)-5-pyrrolidin-1-ylsulfonylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1CCCN1S(=O)(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 IJOFJRNWCALZKL-UHFFFAOYSA-N 0.000 claims description 2
- WBAKOAPFWILXJX-UHFFFAOYSA-N 3-methyl-6-(1-methylbenzimidazole-2-carbonyl)-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(=O)C=3SC=4N(C(N(C)C(=O)C=4C=3SC(C)C)=O)CC(C)C)=NC2=C1 WBAKOAPFWILXJX-UHFFFAOYSA-N 0.000 claims description 2
- BHJLMTLHXPSAQR-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=NC2=C1 BHJLMTLHXPSAQR-UHFFFAOYSA-N 0.000 claims description 2
- BBYYQONNCAAMKA-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)C(C)C)=NC2=C1 BBYYQONNCAAMKA-UHFFFAOYSA-N 0.000 claims description 2
- KJDSEKFFXGDYOD-UHFFFAOYSA-N 5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(pyridine-3-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound OCCCSC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(=O)C1=CC=CN=C1 KJDSEKFFXGDYOD-UHFFFAOYSA-N 0.000 claims description 2
- MQCHNBJYTPUQRP-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CN2C3=CC=CC=C3N=C2)=C1SC1=CC=CS1 MQCHNBJYTPUQRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 14
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 2
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims 1
- JYHUMIJWSGSAPL-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanyl-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound CC(C)SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 JYHUMIJWSGSAPL-UHFFFAOYSA-N 0.000 claims 1
- FVELFONZJZPXTG-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-[(3-oxo-1,2-benzothiazol-2-yl)methyl]-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound S1C2=CC=CC=C2C(=O)N1CC(S1)=C(SC(C)C)C2=C1N(CC(C)C)C(=O)N(C)C2=O FVELFONZJZPXTG-UHFFFAOYSA-N 0.000 claims 1
- DSQHABJZILXDLV-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3SC(C)C)=O)CC(C)C)=NC2=C1 DSQHABJZILXDLV-UHFFFAOYSA-N 0.000 claims 1
- NWMHICYOEMTIFL-OAHLLOKOSA-N 5-[(3r)-3-hydroxypyrrolidin-1-yl]sulfonyl-3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@H](O)CC1)N1S(=O)(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 NWMHICYOEMTIFL-OAHLLOKOSA-N 0.000 claims 1
- YWUBSYGGPJPBOS-UHFFFAOYSA-N 6-(1,3-benzothiazol-2-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2SC(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=NC2=C1 YWUBSYGGPJPBOS-UHFFFAOYSA-N 0.000 claims 1
- FPEQZNUKJTYNCR-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=NC2=CC=CC=C2N1CC(S1)=C(SC(C)C)C2=C1N(CC(C)C)C(=O)N(C)C2=O FPEQZNUKJTYNCR-UHFFFAOYSA-N 0.000 claims 1
- LKJZWOJOQXWWMP-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=NC2=CC=CC=C2N1CC(S1)=CC2=C1N(C(C)C)C(=O)N(C)C2=O LKJZWOJOQXWWMP-UHFFFAOYSA-N 0.000 claims 1
- XFWKMDVLXOAROG-UHFFFAOYSA-N 6-(benzotriazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1=NC2=CC=CC=C2N1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O XFWKMDVLXOAROG-UHFFFAOYSA-N 0.000 claims 1
- HSCFYYZKGKEYCH-UHFFFAOYSA-N 6-(indazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1=CC2=CC=CC=C2N1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O HSCFYYZKGKEYCH-UHFFFAOYSA-N 0.000 claims 1
- SJULOZMZRAUZMG-UHFFFAOYSA-N 6-(indazol-2-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=C2C=CC=CC2=NN1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O SJULOZMZRAUZMG-UHFFFAOYSA-N 0.000 claims 1
- QYOXPODCRHMTOK-UHFFFAOYSA-N 6-[(1,3-dioxoisoindol-2-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CN2C(C3=CC=CC=C3C2=O)=O)=C1SC1=CC=CS1 QYOXPODCRHMTOK-UHFFFAOYSA-N 0.000 claims 1
- CARZRMQRFMKZSE-UHFFFAOYSA-N 6-[(1,4-dioxo-3h-phthalazin-2-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1C(=O)C2=CC=CC=C2C(=O)N1CC(S1)=C(SC(C)C)C2=C1N(CC(C)C)C(=O)N(C)C2=O CARZRMQRFMKZSE-UHFFFAOYSA-N 0.000 claims 1
- UHLNLJGYZGCXIZ-UHFFFAOYSA-N 6-[hydroxy-[6-(trifluoromethyl)pyridin-2-yl]methyl]-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=CSC=1SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CC(C(F)(F)F)=N1 UHLNLJGYZGCXIZ-UHFFFAOYSA-N 0.000 claims 1
- 229910006074 SO2NH2 Inorganic materials 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 213
- 229910052739 hydrogen Inorganic materials 0.000 description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 105
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 77
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 239000000203 mixture Substances 0.000 description 76
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 71
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 61
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 58
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000000284 extract Substances 0.000 description 34
- 239000000377 silicon dioxide Substances 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 27
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 24
- 101150041968 CDC13 gene Proteins 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 20
- 239000012279 sodium borohydride Substances 0.000 description 19
- 229910000033 sodium borohydride Inorganic materials 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 238000004587 chromatography analysis Methods 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
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- FUFBSNYQSJQVET-UHFFFAOYSA-M lithium;3-methyl-1-(2-methylpropyl)-2,4-dioxo-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-5-sulfinate Chemical compound [Li+].[O-]S(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 FUFBSNYQSJQVET-UHFFFAOYSA-M 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
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- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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- 239000011886 peripheral blood Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
- KGAFDVVPNRSBFI-UHFFFAOYSA-N pyrimidine-5-sulfinic acid Chemical compound OS(=O)C1=CN=CN=C1 KGAFDVVPNRSBFI-UHFFFAOYSA-N 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- DSBOPXOKGKIRSG-UHFFFAOYSA-N pyrrolo[3,4-d]pyrimidine-2,4-dione Chemical class O=C1NC(=O)C2=CN=CC2=N1 DSBOPXOKGKIRSG-UHFFFAOYSA-N 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HYOPIVIAUNBSTE-UHFFFAOYSA-N thieno[2,3-d]pyrimidine-6-carbaldehyde Chemical compound N1=CN=C2SC(C=O)=CC2=C1 HYOPIVIAUNBSTE-UHFFFAOYSA-N 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 201000005539 vernal conjunctivitis Diseases 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P13/00—Drugs for disorders of the urinary system
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
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- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Virology (AREA)
- Transplantation (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biomedical Technology (AREA)
- AIDS & HIV (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9802895-4 | 1998-08-28 | ||
| SE9802895 | 1998-08-28 | ||
| PCT/SE1999/001400 WO2000012514A1 (en) | 1998-08-28 | 1999-08-18 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2339664A1 true CA2339664A1 (en) | 2000-03-09 |
Family
ID=20412397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002339664A Abandoned CA2339664A1 (en) | 1998-08-28 | 1999-08-18 | Thieno{2,3,-d}pyrimidinedione derivatives and their use as immunosuppressants |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6300334B1 (enExample) |
| EP (1) | EP1107973B1 (enExample) |
| JP (1) | JP2002523511A (enExample) |
| AT (1) | ATE253580T1 (enExample) |
| AU (1) | AU763758B2 (enExample) |
| CA (1) | CA2339664A1 (enExample) |
| DE (1) | DE69912618T2 (enExample) |
| DK (1) | DK1107973T3 (enExample) |
| ES (1) | ES2211161T3 (enExample) |
| NZ (1) | NZ509809A (enExample) |
| PT (1) | PT1107973E (enExample) |
| WO (1) | WO2000012514A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9801399D0 (sv) | 1998-04-21 | 1998-04-21 | Astra Pharma Prod | Method and apparatus for filling containers |
| ATE272642T1 (de) * | 2000-05-04 | 2004-08-15 | Astrazeneca Ab | Thieno(2,3-d)pyrimidindione und ihre verwendung als pharmazeutische mittel |
| GB2361917A (en) * | 2000-05-04 | 2001-11-07 | Astrazeneca Ab | Novel thieno[2,3-d]pyrimidinediones |
| GB2363377B (en) * | 2000-06-14 | 2004-06-09 | Astrazeneca Ab | Novel thieno[2,3-d]pyrimidinediones and therapeutic uses thereof |
| BR0207216A (pt) * | 2001-02-14 | 2004-03-09 | Warner Lambert Co | Derivados de tieno 2,3-d-pirimidindiona como inibidores de metaloproteinase matriz |
| GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| SE0300119D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| WO2004065395A1 (en) * | 2003-01-17 | 2004-08-05 | Astrazeneca Ab | Thienopyridazinones and their use in modulation of autoimmune disease |
| CN1925855B (zh) | 2003-12-19 | 2010-06-16 | 普莱希科公司 | 开发Ret调节剂的化合物和方法 |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| EP1768662A2 (en) | 2004-06-24 | 2007-04-04 | Novartis Vaccines and Diagnostics, Inc. | Small molecule immunopotentiators and assays for their detection |
| EP1989210A2 (en) * | 2006-03-02 | 2008-11-12 | Cv Therapeutics, Inc. | A2a adenosine receptor antagonists |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| EP2170830B1 (en) | 2007-07-17 | 2014-10-15 | Plexxikon, Inc. | 2-FLUORO-BENZENESULFONAMIDE COMPOUNDS AS Raf KINASE MODULATORS |
| AU2010227225A1 (en) * | 2009-03-23 | 2011-09-15 | Glenmark Pharmaceuticals, S.A. | Furopyrimidinedione derivatives as TRPA1 modulators |
| KR20170058465A (ko) | 2009-04-03 | 2017-05-26 | 에프. 호프만-라 로슈 아게 | 프로판-１-술폰산 ｛３-［５-（４-클로로-페닐）-１Ｈ-피롤로［２，３-ｂ］피리딘-３-카르보닐］-２，４-디플루오로-페닐｝-아미드 조성물 및 그의 용도 |
| AU2010315126B2 (en) | 2009-11-06 | 2015-06-25 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2012109075A1 (en) | 2011-02-07 | 2012-08-16 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| TWI558702B (zh) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | 醫藥活性物質的固態形式 |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| MX2016004250A (es) * | 2013-10-07 | 2016-07-12 | Bayer Pharma AG | Tienouracilcarboxamidas ciclicas y usos de las mismas. |
| UY36586A (es) | 2015-03-26 | 2016-10-31 | Bayer Pharma AG | Heterociclilmetiltienouracilos y uso de los mismos |
| WO2018041771A1 (de) | 2016-09-02 | 2018-03-08 | Bayer Pharma Aktiengesellschaft | (1-methylcyclopropyl)methyl-substituierte thienouracile und ihre verwendung |
| RU2019111357A (ru) | 2016-09-23 | 2020-10-23 | Байер Акциенгезельшафт | N3-циклически замещенные тиеноурацилы и их применение |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01213284A (ja) * | 1988-02-22 | 1989-08-28 | Sankyo Co Ltd | チエノピリミジン−２，４−ジオン誘導体 |
| DD293824A5 (de) | 1990-04-24 | 1991-09-12 | Karl-Marx-Universitaet Leipzig,De | Verfahren zur herstellung von 3-(mercaptoalkyl)=thieno/2,3-d/pyrimidin-2,4(1h,3h)-dionen |
| TW276256B (enExample) * | 1993-08-26 | 1996-05-21 | Takeda Pharm Industry Co Ltd |
-
1999
- 1999-08-18 WO PCT/SE1999/001400 patent/WO2000012514A1/en not_active Ceased
- 1999-08-18 CA CA002339664A patent/CA2339664A1/en not_active Abandoned
- 1999-08-18 PT PT99944964T patent/PT1107973E/pt unknown
- 1999-08-18 EP EP99944964A patent/EP1107973B1/en not_active Expired - Lifetime
- 1999-08-18 AT AT99944964T patent/ATE253580T1/de not_active IP Right Cessation
- 1999-08-18 DE DE69912618T patent/DE69912618T2/de not_active Expired - Fee Related
- 1999-08-18 NZ NZ509809A patent/NZ509809A/xx unknown
- 1999-08-18 JP JP2000567536A patent/JP2002523511A/ja active Pending
- 1999-08-18 DK DK99944964T patent/DK1107973T3/da active
- 1999-08-18 ES ES99944964T patent/ES2211161T3/es not_active Expired - Lifetime
- 1999-08-18 AU AU57677/99A patent/AU763758B2/en not_active Ceased
- 1999-08-18 US US09/402,837 patent/US6300334B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1107973B1 (en) | 2003-11-05 |
| ATE253580T1 (de) | 2003-11-15 |
| AU763758B2 (en) | 2003-07-31 |
| AU5767799A (en) | 2000-03-21 |
| DE69912618D1 (de) | 2003-12-11 |
| DE69912618T2 (de) | 2004-10-28 |
| JP2002523511A (ja) | 2002-07-30 |
| ES2211161T3 (es) | 2004-07-01 |
| PT1107973E (pt) | 2004-03-31 |
| WO2000012514A1 (en) | 2000-03-09 |
| US6300334B1 (en) | 2001-10-09 |
| DK1107973T3 (da) | 2004-02-23 |
| EP1107973A1 (en) | 2001-06-20 |
| NZ509809A (en) | 2002-11-26 |
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