ES2268059T3 - Tieno (2,3-d) pirimidindionas como inhibidores de la proliferacion de celulas t. - Google Patents
Tieno (2,3-d) pirimidindionas como inhibidores de la proliferacion de celulas t. Download PDFInfo
- Publication number
- ES2268059T3 ES2268059T3 ES02745634T ES02745634T ES2268059T3 ES 2268059 T3 ES2268059 T3 ES 2268059T3 ES 02745634 T ES02745634 T ES 02745634T ES 02745634 T ES02745634 T ES 02745634T ES 2268059 T3 ES2268059 T3 ES 2268059T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- pyrimidin
- methoxy
- dioxo
- tetrahydro
- 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.)
- Expired - Lifetime
Links
- 230000035755 proliferation Effects 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 2
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 313
- 150000001875 compounds Chemical class 0.000 claims abstract description 269
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 89
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 83
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 52
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 34
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 34
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 33
- 125000001424 substituent group Chemical group 0.000 claims abstract description 31
- 125000003118 aryl group Chemical group 0.000 claims abstract description 29
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 27
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 26
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000001301 oxygen Chemical group 0.000 claims abstract description 25
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000011593 sulfur Chemical group 0.000 claims abstract description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 21
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 18
- 150000002367 halogens Chemical class 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 125000005843 halogen group Chemical group 0.000 claims abstract description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
- 125000004385 trihaloalkyl group Chemical group 0.000 claims abstract description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
- 125000004982 dihaloalkyl group Chemical group 0.000 claims abstract description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 14
- 125000000464 thioxo group Chemical group S=* 0.000 claims abstract description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 12
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 11
- 125000006413 ring segment Chemical group 0.000 claims abstract description 11
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims abstract description 10
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 123
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 107
- 238000000034 method Methods 0.000 claims description 106
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 78
- QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims description 64
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 21
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 12
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000005493 quinolyl group Chemical group 0.000 claims description 10
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- LBBGSBPIRZEZSY-UHFFFAOYSA-N 6-(1h-indol-3-ylmethyl)-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3NC=1)=C2C(=O)N(C)OC LBBGSBPIRZEZSY-UHFFFAOYSA-N 0.000 claims description 4
- JWJLXCMYIXOEKN-UHFFFAOYSA-N 6-(2h-indazol-3-ylmethyl)-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3NN=1)=C2C(=O)N(C)OC JWJLXCMYIXOEKN-UHFFFAOYSA-N 0.000 claims description 4
- CMLJYPLKIKPWDF-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C(C)=NC(Cl)=C1Cl CMLJYPLKIKPWDF-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- OZGWACQETOIWCE-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CN=C3NC=1)=C2C(=O)N(C)OC OZGWACQETOIWCE-UHFFFAOYSA-N 0.000 claims description 4
- CWEFUJMDBUNBKZ-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2,4,5-trichloroimidazol-1-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C(Cl)=NC(Cl)=C1Cl CWEFUJMDBUNBKZ-UHFFFAOYSA-N 0.000 claims description 4
- BLZGLDJQMDPSMB-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-propylbenzimidazol-1-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C3=CC=CC=C3N=C1CCC)=C2C(=O)N(C)OC BLZGLDJQMDPSMB-UHFFFAOYSA-N 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- HNGUIAIZYGMWAI-UHFFFAOYSA-N 1-(2,2-dimethylpropyl)-n-methoxy-n,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3N=CC=1)=C2C(=O)N(C)OC HNGUIAIZYGMWAI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
- KKZUMAMOMRDVKA-UHFFFAOYSA-N 2-chloropropane Chemical group [CH2]C(C)Cl KKZUMAMOMRDVKA-UHFFFAOYSA-N 0.000 claims description 3
- SFXOTKPNEUNUFM-UHFFFAOYSA-N 6-(1h-indole-3-carbonyl)-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound C1=CC=C2C(C(=O)C3=C(C=4C(=O)N(C)C(=O)N(CC(C)C)C=4S3)C(=O)N(C)OC)=CNC2=C1 SFXOTKPNEUNUFM-UHFFFAOYSA-N 0.000 claims description 3
- SQEPUNKKDKMSHT-UHFFFAOYSA-N 6-[(3-chloroquinolin-4-yl)methyl]-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3N=CC=1Cl)=C2C(=O)N(C)OC SQEPUNKKDKMSHT-UHFFFAOYSA-N 0.000 claims description 3
- VIDVFTXECDAGAM-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-ethyl-n-methoxy-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(OC)CC)=C1CN1C(C)=NC(Cl)=C1Cl VIDVFTXECDAGAM-UHFFFAOYSA-N 0.000 claims description 3
- VZMVSPBAUSGBBT-UHFFFAOYSA-N 6-[[4,5-dichloro-2-(hydroxymethyl)imidazol-1-yl]methyl]-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C(CO)=NC(Cl)=C1Cl VZMVSPBAUSGBBT-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- FQXRBDBNEITFPH-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-oxo-1,3-benzothiazol-3-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C(SC3=CC=CC=C31)=O)=C2C(=O)N(C)OC FQXRBDBNEITFPH-UHFFFAOYSA-N 0.000 claims description 3
- GQLKYTHLQYPEBI-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-6-[(2-methylsulfanylimidazol-1-yl)methyl]-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C=CN=C1SC GQLKYTHLQYPEBI-UHFFFAOYSA-N 0.000 claims description 3
- BZKSHTJFQWYDQL-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[(2-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2,4-dioxo-1-propan-2-ylthieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)N1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CN=C3NC=1C)=C2C(=O)N(C)OC BZKSHTJFQWYDQL-UHFFFAOYSA-N 0.000 claims description 3
- ZAEYEOOWSNCQAZ-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[(3-methyl-2-oxobenzimidazol-1-yl)methyl]-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C(N(C)C3=CC=CC=C31)=O)=C2C(=O)N(C)OC ZAEYEOOWSNCQAZ-UHFFFAOYSA-N 0.000 claims description 3
- QXICFGCADMCHQD-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[[2-(methylamino)benzimidazol-1-yl]methyl]-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C3=CC=CC=C3N=C1NC)=C2C(=O)N(C)OC QXICFGCADMCHQD-UHFFFAOYSA-N 0.000 claims description 3
- 230000025020 negative regulation of T cell proliferation Effects 0.000 claims description 3
- AYZHIPAPDNBZJQ-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-propan-2-ylimidazol-1-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C=CN=C1C(C)C AYZHIPAPDNBZJQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
- 229920006395 saturated elastomer Polymers 0.000 abstract description 4
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 abstract description 2
- 125000004122 cyclic group Chemical group 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
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- 238000004949 mass spectrometry Methods 0.000 description 106
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- 239000000243 solution Substances 0.000 description 59
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- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 28
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0117583.5A GB0117583D0 (en) | 2001-07-19 | 2001-07-19 | Novel compounds |
| GB0117583 | 2001-07-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2268059T3 true ES2268059T3 (es) | 2007-03-16 |
Family
ID=9918788
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02745634T Expired - Lifetime ES2268059T3 (es) | 2001-07-19 | 2002-07-16 | Tieno (2,3-d) pirimidindionas como inhibidores de la proliferacion de celulas t. |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7361660B2 (enExample) |
| EP (1) | EP1412362B1 (enExample) |
| JP (1) | JP2004537557A (enExample) |
| AT (1) | ATE334988T1 (enExample) |
| DE (1) | DE60213609T2 (enExample) |
| ES (1) | ES2268059T3 (enExample) |
| GB (1) | GB0117583D0 (enExample) |
| WO (1) | WO2003008422A1 (enExample) |
Families Citing this family (65)
| 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 |
| GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| WO2004065395A1 (en) * | 2003-01-17 | 2004-08-05 | Astrazeneca Ab | Thienopyridazinones and their use in modulation of autoimmune disease |
| SE0300119D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| 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 |
| US8017395B2 (en) | 2004-12-17 | 2011-09-13 | Lifescan, Inc. | Seeding cells on porous supports |
| MX2007014377A (es) | 2005-05-17 | 2008-02-06 | Plexxikon Inc | Inhibidores de proteina cinasa de derivados de pirrol (2,3-b) piridina. |
| AU2006202209B2 (en) | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
| WO2006133052A2 (en) * | 2005-06-08 | 2006-12-14 | Centocor, Inc. | A cellular therapy for ocular degeneration |
| DK2395004T3 (en) | 2005-06-22 | 2016-03-21 | Plexxikon Inc | Pyrrolo [2,3-b] pyridine derivatives as protein kinase inhibitors |
| US20070122448A1 (en) * | 2005-11-28 | 2007-05-31 | Alireza Rezania | Compositions and methods to create a vascularized environment for cellular transplantation |
| EP2021462B1 (en) | 2006-04-28 | 2019-01-09 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
| US8741643B2 (en) * | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| KR20090115142A (ko) * | 2007-01-30 | 2009-11-04 | 유니버시티 오브 조지아 리서치 파운데이션, 인코포레이티드 | 초기 중배엽 세포，내배엽 및 중배엽 계통의 생성에 유용한 중내배엽 세포의 안정한 집단 및 다능성 유주 세포（ｍｍｃ） |
| US9080145B2 (en) * | 2007-07-01 | 2015-07-14 | Lifescan Corporation | Single pluripotent stem cell culture |
| CN104250632B (zh) | 2007-07-01 | 2018-09-11 | 生命扫描有限公司 | 单个多能干细胞培养 |
| EP2170830B1 (en) | 2007-07-17 | 2014-10-15 | Plexxikon, Inc. | 2-FLUORO-BENZENESULFONAMIDE COMPOUNDS AS Raf KINASE MODULATORS |
| CA2693156C (en) | 2007-07-18 | 2018-03-06 | Alireza Rezania | Differentiation of human embryonic stem cells |
| JP5769965B2 (ja) * | 2007-07-31 | 2015-08-26 | ライフスキャン・インコーポレイテッドＬｉｆｅｓｃａｎ，Ｉｎｃ． | ヒト胚性幹細胞の分化 |
| CN101878298B (zh) * | 2007-11-27 | 2017-08-15 | 生命扫描有限公司 | 人胚胎干细胞的分化 |
| KR101597731B1 (ko) | 2008-02-21 | 2016-02-26 | 센토코 오르토 바이오테크 인코포레이티드 | 세포 부착, 배양 및 탈리를 위한 방법, 표면 개질 플레이트 및 조성물 |
| US20090220995A1 (en) | 2008-02-28 | 2009-09-03 | Sachs David H | Multiple administrations of umbilicus derived cells |
| US8623648B2 (en) * | 2008-04-24 | 2014-01-07 | Janssen Biotech, Inc. | Treatment of pluripotent cells |
| AU2009267137A1 (en) * | 2008-06-30 | 2010-01-07 | Centocor Ortho Biotech Inc. | Differentiation of pluripotent stem cells |
| US20110305672A1 (en) | 2008-07-25 | 2011-12-15 | University Of Georgia Research Foundation, Inc. | COMPOSITIONS FOR MESODERM DERIVED ISL1+ MULTIPOTENT CELLS (IMPs), EPICARDIAL PROGENITOR CELLS (EPCs) AND MULTIPOTENT CD56C CELLS (C56Cs) AND METHODS OF PRODUCING AND USING SAME |
| WO2010011352A2 (en) | 2008-07-25 | 2010-01-28 | The University Of Georgia Research Foundation, Inc. | Compositions for mesoderm derived isl1+ multipotent cells (imps), epicardial progenitor cells (epcs) and multipotent cxcr4+cd56+ cells (c56cs) and methods of use |
| US20100028307A1 (en) * | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
| BRPI0919885A2 (pt) * | 2008-10-31 | 2015-08-11 | Centocor Ortho Biotech Inc | Diferenciação de células-tronco embrionárias humanas para a linhagem endócrina pancreática |
| KR102025158B1 (ko) * | 2008-10-31 | 2019-09-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 췌장 내분비 계통으로의 분화 |
| PL2366022T3 (pl) * | 2008-11-20 | 2016-11-30 | Sposoby i kompozycje do przyłączania i hodowli komórek na podłożach planarnych | |
| JP2012509085A (ja) | 2008-11-20 | 2012-04-19 | ヤンセン バイオテツク，インコーポレーテツド | マイクロキャリア上での多能性幹細胞の培養 |
| 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 |
| AU2010276438B2 (en) | 2009-07-20 | 2015-06-11 | Janssen Biotech Inc. | Differentiation of human embryonic stem cells |
| SG177483A1 (en) * | 2009-07-20 | 2012-02-28 | Janssen Biotech Inc | Differentiation of human embryonic stem cells |
| CN103952372B (zh) | 2009-07-20 | 2016-10-05 | 詹森生物科技公司 | 人胚胎干细胞的分化 |
| AU2010315126B2 (en) | 2009-11-06 | 2015-06-25 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| KR101841271B1 (ko) * | 2009-12-23 | 2018-03-22 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
| EP4410991A3 (en) | 2009-12-23 | 2024-10-09 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
| KR20130025375A (ko) * | 2010-03-01 | 2013-03-11 | 얀센 바이오테크 인코포레이티드 | 만능 줄기 세포로부터 유래된 세포의 정제 방법 |
| WO2011143299A2 (en) | 2010-05-12 | 2011-11-17 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells |
| CA2807158C (en) | 2010-08-12 | 2025-10-07 | Janssen Biotech Inc | Treatment of diabetes with pancreatic endocrine precursor cells |
| PH12013500389A1 (en) | 2010-08-31 | 2013-04-22 | Janssen Biotech Inc | Differentiation of human embryonic stem cells |
| PH12013500349A1 (en) | 2010-08-31 | 2022-03-30 | Janssen Biotech Inc | Differentiation of pluripotent stem cells |
| WO2012030538A2 (en) | 2010-08-31 | 2012-03-08 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
| CA2816495C (en) | 2010-12-15 | 2020-10-13 | Kadimastem Ltd. | Insulin producing cells derived from pluripotent stem cells |
| 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 |
| JP6441080B2 (ja) | 2011-12-22 | 2018-12-19 | ヤンセン バイオテツク，インコーポレーテツド | 単一ホルモンのインスリン陽性細胞へのヒト胚性幹細胞の分化 |
| JP6383292B2 (ja) | 2012-03-07 | 2018-08-29 | ヤンセン バイオテツク，インコーポレーテツド | 多能性幹細胞の増殖及び維持のための明確な培地 |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| MX358590B (es) | 2012-06-08 | 2018-08-24 | Janssen Biotech Inc | Diferenciacion de celulas madre embrionarias humanas en celulas endocrinas pancreaticas. |
| JP6557147B2 (ja) | 2012-12-31 | 2019-08-07 | ヤンセン バイオテツク，インコーポレーテツド | Ｈｂ９調節物を用いたヒト胚性幹細胞の膵臓内分泌細胞への分化 |
| US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
| EP2938722B1 (en) | 2012-12-31 | 2021-12-08 | Janssen Biotech, Inc. | Suspension and clustering of human pluripotent cells for differentiation into pancreatic endocrine cells |
| SG10201709338RA (en) | 2012-12-31 | 2017-12-28 | Janssen Biotech Inc | Culturing of human embryonic stem cells at the air-liquid interface for differentiation into pancreatic endocrine cells |
| WO2014159662A1 (en) | 2013-03-13 | 2014-10-02 | University Of Miami | Method for isolation and purification of microvesicles from cell culture supernatants and biological fluids |
| CN117821369A (zh) | 2014-05-16 | 2024-04-05 | 詹森生物科技公司 | 小分子增强胰腺内分泌细胞中的mafa表达的用途 |
| EP4231015B1 (en) | 2015-11-30 | 2024-10-30 | Kadimastem Ltd. | Methods for differentiating and purifying pancreatic endocrine cells |
| MA45479A (fr) | 2016-04-14 | 2019-02-20 | Janssen Biotech Inc | Différenciation de cellules souches pluripotentes en cellules de l'endoderme de l'intestin moyen |
| AU2021327376A1 (en) | 2020-08-21 | 2023-04-20 | University Of Miami | Compositions and methods of treatment using microvesicles from bone marrow-derived mesenchymal stem cells |
| EP4511045A1 (en) | 2022-04-19 | 2025-02-26 | University of Miami | Compositions comprising microvesicles for use in the prevention and treatment of graft versus host disease |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6469014B1 (en) * | 1997-05-28 | 2002-10-22 | Astrazeneca Ab | Thieno[2,3-d] pyrimidinediones, their preparation and use in therapy |
| SE9702001D0 (sv) | 1997-05-28 | 1997-05-28 | Astra Pharma Prod | Novel compounds |
| DE19738855C2 (de) * | 1997-09-05 | 2001-01-04 | Lohmann Therapie Syst Lts | Transdermales therapeutisches System mit haftklebender Reservoirschicht und unidirektional elastischer Rückschicht |
| EP1036076B1 (en) | 1997-12-05 | 2002-09-04 | AstraZeneca UK Limited | Novel compounds |
| US6232320B1 (en) | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| WO2000012514A1 (en) | 1998-08-28 | 2000-03-09 | Astrazeneca Ab | Novel compounds |
| 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 |
-
2001
- 2001-07-19 GB GBGB0117583.5A patent/GB0117583D0/en not_active Ceased
-
2002
- 2002-07-16 EP EP02745634A patent/EP1412362B1/en not_active Expired - Lifetime
- 2002-07-16 JP JP2003513981A patent/JP2004537557A/ja active Pending
- 2002-07-16 ES ES02745634T patent/ES2268059T3/es not_active Expired - Lifetime
- 2002-07-16 WO PCT/GB2002/003250 patent/WO2003008422A1/en not_active Ceased
- 2002-07-16 AT AT02745634T patent/ATE334988T1/de not_active IP Right Cessation
- 2002-07-16 DE DE60213609T patent/DE60213609T2/de not_active Expired - Fee Related
- 2002-07-16 US US10/483,161 patent/US7361660B2/en not_active Expired - Fee Related
-
2008
- 2008-02-28 US US12/039,204 patent/US20080153855A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20080153855A1 (en) | 2008-06-26 |
| JP2004537557A (ja) | 2004-12-16 |
| DE60213609D1 (de) | 2006-09-14 |
| US7361660B2 (en) | 2008-04-22 |
| ATE334988T1 (de) | 2006-08-15 |
| DE60213609T2 (de) | 2007-08-16 |
| GB0117583D0 (en) | 2001-09-12 |
| WO2003008422A1 (en) | 2003-01-30 |
| EP1412362A1 (en) | 2004-04-28 |
| HK1065542A1 (en) | 2005-02-25 |
| EP1412362B1 (en) | 2006-08-02 |
| US20040171623A1 (en) | 2004-09-02 |
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