MXPA05006921A - Agentes terapeuticos. - Google Patents
Agentes terapeuticos.Info
- Publication number
- MXPA05006921A MXPA05006921A MXPA05006921A MXPA05006921A MXPA05006921A MX PA05006921 A MXPA05006921 A MX PA05006921A MX PA05006921 A MXPA05006921 A MX PA05006921A MX PA05006921 A MXPA05006921 A MX PA05006921A MX PA05006921 A MXPA05006921 A MX PA05006921A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- alkyl
- carbon
- amino
- carbamoyl
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 18
- 229940124597 therapeutic agent Drugs 0.000 title description 3
- 241001465754 Metazoa Species 0.000 claims abstract description 20
- 108010090091 TIE-2 Receptor Proteins 0.000 claims abstract description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 589
- -1 trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 204
- 150000001875 compounds Chemical class 0.000 claims description 137
- 229910052799 carbon Inorganic materials 0.000 claims description 105
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 101
- 229910052757 nitrogen Inorganic materials 0.000 claims description 57
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000003282 alkyl amino group Chemical group 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 17
- 102000012753 TIE-2 Receptor Human genes 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- 125000001589 carboacyl group Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 14
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 14
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 13
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
- 230000001772 anti-angiogenic effect Effects 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 229910052779 Neodymium Inorganic materials 0.000 claims description 7
- 125000006319 alkynyl amino group Chemical group 0.000 claims description 7
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 238000003780 insertion Methods 0.000 claims description 5
- 230000037431 insertion Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 3
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- 230000001143 conditioned effect Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 2
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 58
- 239000007787 solid Substances 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 238000001819 mass spectrum Methods 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
- 238000000034 method Methods 0.000 description 41
- 238000007429 general method Methods 0.000 description 35
- 239000000243 solution Substances 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 238000000746 purification Methods 0.000 description 32
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 31
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
- 239000000203 mixture Substances 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 27
- 239000003446 ligand Substances 0.000 description 27
- 229920002554 vinyl polymer Polymers 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 206010028980 Neoplasm Diseases 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 230000008569 process Effects 0.000 description 22
- 108020003175 receptors Proteins 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- 102000005962 receptors Human genes 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 238000011282 treatment Methods 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 230000000694 effects Effects 0.000 description 17
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- 201000011510 cancer Diseases 0.000 description 15
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 241000282414 Homo sapiens Species 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 13
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 12
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 12
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 229960005419 nitrogen Drugs 0.000 description 11
- GHCFWKFREBNSPC-UHFFFAOYSA-N 2-Amino-4-methylpyrimidine Chemical compound CC1=CC=NC(N)=N1 GHCFWKFREBNSPC-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 230000033115 angiogenesis Effects 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 210000002889 endothelial cell Anatomy 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 230000026731 phosphorylation Effects 0.000 description 10
- 238000006366 phosphorylation reaction Methods 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 108091000080 Phosphotransferase Proteins 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000035578 autophosphorylation Effects 0.000 description 9
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- 230000018109 developmental process Effects 0.000 description 9
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- 102000020233 phosphotransferase Human genes 0.000 description 9
- INHDZCYGOGPCBM-VOTSOKGWSA-N 5-[(e)-2-(2-chloropyrimidin-4-yl)ethenyl]-6-phenylimidazo[2,1-b][1,3]thiazole Chemical compound ClC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 INHDZCYGOGPCBM-VOTSOKGWSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
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- 102100034594 Angiopoietin-1 Human genes 0.000 description 7
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- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 7
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 7
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- 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
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- 239000007858 starting material Substances 0.000 description 7
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- RRHHDLZBYCPJAW-UHFFFAOYSA-N 6-phenylimidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound N1=C2SC=CN2C(C=O)=C1C1=CC=CC=C1 RRHHDLZBYCPJAW-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
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- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
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- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
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- 230000000699 topical effect Effects 0.000 description 1
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- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
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- 231100000419 toxicity Toxicity 0.000 description 1
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- 238000010361 transduction Methods 0.000 description 1
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- 238000011830 transgenic mouse model Methods 0.000 description 1
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- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0230089.5A GB0230089D0 (en) | 2002-12-24 | 2002-12-24 | Therapeutic agents |
| PCT/GB2003/005568 WO2004058776A1 (en) | 2002-12-24 | 2003-12-19 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA05006921A true MXPA05006921A (es) | 2005-08-18 |
Family
ID=9950374
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA05006921A MXPA05006921A (es) | 2002-12-24 | 2003-12-19 | Agentes terapeuticos. |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20060069109A1 (enExample) |
| EP (1) | EP1575963B1 (enExample) |
| JP (1) | JP2006515593A (enExample) |
| KR (1) | KR20050087852A (enExample) |
| CN (1) | CN1751052A (enExample) |
| AT (1) | ATE394403T1 (enExample) |
| AU (1) | AU2003295135A1 (enExample) |
| BR (1) | BR0317708A (enExample) |
| CA (1) | CA2508917A1 (enExample) |
| DE (1) | DE60320849D1 (enExample) |
| ES (1) | ES2305548T3 (enExample) |
| GB (1) | GB0230089D0 (enExample) |
| MX (1) | MXPA05006921A (enExample) |
| NO (1) | NO20052989L (enExample) |
| WO (1) | WO2004058776A1 (enExample) |
| ZA (1) | ZA200504827B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7776869B2 (en) | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
| GB0502418D0 (en) * | 2005-02-05 | 2005-03-16 | Astrazeneca Ab | Compounds |
| SI1973545T1 (sl) * | 2005-12-23 | 2013-04-30 | Ariad Pharmaceuticals, Inc. | Spojine bicikličnega heteroarila |
| ES2761180T3 (es) * | 2005-12-23 | 2020-05-19 | Ariad Pharma Inc | Compuestos bicíclicos de heteroarilo |
| AU2015210454B2 (en) * | 2005-12-23 | 2016-10-27 | Takeda Pharmaceuticals U.S.A., Inc. | Bicyclic heteroaryl compounds |
| US8278307B2 (en) | 2006-05-08 | 2012-10-02 | Ariad Pharmaceuticals, Inc. | Monocyclic Heteroaryl compounds |
| WO2007133560A2 (en) | 2006-05-08 | 2007-11-22 | Ariad Pharmaceuticals, Inc. | Acetylenic heteroaryl compounds |
| EP2120964A2 (en) | 2006-12-15 | 2009-11-25 | Abraxis BioScience, Inc. | Triazine derivatives and their therapeutical applications |
| CA2729012A1 (en) | 2008-06-27 | 2009-12-30 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| JP5590040B2 (ja) | 2008-11-12 | 2014-09-17 | アリアド・ファーマシューティカルズ・インコーポレイテッド | キナーゼ阻害剤としてのピラジノピラジンおよび誘導体 |
| JP2012529517A (ja) | 2009-06-09 | 2012-11-22 | アブラクシス バイオサイエンス リミテッド ライアビリティー カンパニー | ベンジル置換トリアジン誘導体類及びそれらの治療応用 |
| KR101457027B1 (ko) | 2009-06-09 | 2014-10-31 | 캘리포니아 캐피탈 에쿼티, 엘엘씨 | 트리아진 유도체와 이들의 치료적 용도 |
| EP2308866A1 (de) | 2009-10-09 | 2011-04-13 | Bayer CropScience AG | Phenylpyri(mi)dinylpyrazole und ihre Verwendung als Fungizide |
| EP2508511A1 (en) * | 2011-04-07 | 2012-10-10 | Laboratoire Biodim | Inhibitors of viral replication, their process of preparation and their therapeutical uses |
| BR112014028006A2 (pt) * | 2012-05-30 | 2017-06-27 | Hoffmann La Roche | heterociclos de pirrolidino |
| CA3167093A1 (en) | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| DK4013502T3 (da) * | 2019-08-16 | 2025-11-10 | Cyclacel Pharmaceuticals Inc | Fremgangsmåde til fremstillingen af et pyrimidino-diazepinderivat |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ517758A (en) * | 1999-09-17 | 2004-06-25 | Abbott Gmbh & Co | Pyrazolopyrimidines useful as therapeutic agents |
| KR20020050294A (ko) * | 1999-11-22 | 2002-06-26 | 피터 기딩스 | 신규화합물 |
| EP1343779B1 (en) * | 2000-11-20 | 2007-06-27 | Smithkline Beecham Corporation | Novel compounds |
| DE60304718T2 (de) * | 2002-08-06 | 2007-04-26 | Astrazeneca Ab | Kondensierte pyridine und pyrimidine mit tie2 (tek) aktivität |
-
2002
- 2002-12-24 GB GBGB0230089.5A patent/GB0230089D0/en not_active Ceased
-
2003
- 2003-12-19 WO PCT/GB2003/005568 patent/WO2004058776A1/en not_active Ceased
- 2003-12-19 AT AT03786136T patent/ATE394403T1/de not_active IP Right Cessation
- 2003-12-19 BR BR0317708-4A patent/BR0317708A/pt not_active Application Discontinuation
- 2003-12-19 EP EP03786136A patent/EP1575963B1/en not_active Expired - Lifetime
- 2003-12-19 ES ES03786136T patent/ES2305548T3/es not_active Expired - Lifetime
- 2003-12-19 DE DE60320849T patent/DE60320849D1/de not_active Expired - Fee Related
- 2003-12-19 JP JP2004563345A patent/JP2006515593A/ja active Pending
- 2003-12-19 CN CNA2003801098327A patent/CN1751052A/zh active Pending
- 2003-12-19 US US10/540,348 patent/US20060069109A1/en not_active Abandoned
- 2003-12-19 AU AU2003295135A patent/AU2003295135A1/en not_active Abandoned
- 2003-12-19 KR KR1020057011870A patent/KR20050087852A/ko not_active Withdrawn
- 2003-12-19 CA CA002508917A patent/CA2508917A1/en not_active Abandoned
- 2003-12-19 MX MXPA05006921A patent/MXPA05006921A/es unknown
-
2005
- 2005-06-13 ZA ZA200504827A patent/ZA200504827B/en unknown
- 2005-06-17 NO NO20052989A patent/NO20052989L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200504827B (en) | 2006-04-26 |
| CA2508917A1 (en) | 2004-07-15 |
| EP1575963B1 (en) | 2008-05-07 |
| BR0317708A (pt) | 2005-11-22 |
| US20060069109A1 (en) | 2006-03-30 |
| JP2006515593A (ja) | 2006-06-01 |
| AU2003295135A1 (en) | 2004-07-22 |
| KR20050087852A (ko) | 2005-08-31 |
| EP1575963A1 (en) | 2005-09-21 |
| NO20052989L (no) | 2005-07-21 |
| ATE394403T1 (de) | 2008-05-15 |
| DE60320849D1 (de) | 2008-06-19 |
| ES2305548T3 (es) | 2008-11-01 |
| CN1751052A (zh) | 2006-03-22 |
| NO20052989D0 (no) | 2005-06-17 |
| WO2004058776A1 (en) | 2004-07-15 |
| GB0230089D0 (en) | 2003-01-29 |
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