KR20050087852A - 치료제 - Google Patents
치료제 Download PDFInfo
- Publication number
- KR20050087852A KR20050087852A KR1020057011870A KR20057011870A KR20050087852A KR 20050087852 A KR20050087852 A KR 20050087852A KR 1020057011870 A KR1020057011870 A KR 1020057011870A KR 20057011870 A KR20057011870 A KR 20057011870A KR 20050087852 A KR20050087852 A KR 20050087852A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- amino
- carbamoyl
- heterocyclyl
- formula
- 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.)
- Withdrawn
Links
- 239000003814 drug Substances 0.000 title claims description 20
- 229940124597 therapeutic agent Drugs 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 145
- 108010090091 TIE-2 Receptor Proteins 0.000 claims abstract description 23
- 241001465754 Metazoa Species 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 258
- -1 trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 212
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 37
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000003282 alkyl amino group Chemical group 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 18
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 17
- 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
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 13
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 230000001772 anti-angiogenic effect Effects 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 238000003780 insertion Methods 0.000 claims description 5
- 230000037431 insertion Effects 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- 125000002947 alkylene 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
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 102000012753 TIE-2 Receptor Human genes 0.000 abstract description 12
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 abstract description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 59
- 238000001819 mass spectrum Methods 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- 239000007787 solid Substances 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 238000000034 method Methods 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 44
- 238000007429 general method Methods 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 31
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 28
- 238000000746 purification Methods 0.000 description 28
- 239000003446 ligand Substances 0.000 description 27
- 239000000203 mixture Substances 0.000 description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 206010028980 Neoplasm Diseases 0.000 description 24
- 239000013067 intermediate product Substances 0.000 description 24
- 239000000377 silicon dioxide Substances 0.000 description 23
- 238000003818 flash chromatography Methods 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 102000005962 receptors Human genes 0.000 description 21
- 239000002904 solvent Substances 0.000 description 19
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 201000011510 cancer Diseases 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 230000008569 process Effects 0.000 description 14
- 229920002554 vinyl polymer Polymers 0.000 description 14
- 206010029113 Neovascularisation Diseases 0.000 description 13
- 210000002889 endothelial cell Anatomy 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 230000033115 angiogenesis Effects 0.000 description 11
- 230000035578 autophosphorylation Effects 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 229960005419 nitrogen Drugs 0.000 description 11
- 230000026731 phosphorylation Effects 0.000 description 11
- 238000006366 phosphorylation reaction Methods 0.000 description 11
- 230000019491 signal transduction Effects 0.000 description 11
- 230000002792 vascular Effects 0.000 description 11
- 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 10
- 241000282412 Homo Species 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 108091000080 Phosphotransferase Proteins 0.000 description 9
- MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 102000020233 phosphotransferase Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- GHCFWKFREBNSPC-UHFFFAOYSA-N 2-Amino-4-methylpyrimidine Chemical compound CC1=CC=NC(N)=N1 GHCFWKFREBNSPC-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 8
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- HLTBNGFCRFBYPW-UHFFFAOYSA-N 3-methyl-5-phenylimidazole-4-carbaldehyde Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1C=O HLTBNGFCRFBYPW-UHFFFAOYSA-N 0.000 description 7
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 7
- 108010073929 Vascular Endothelial Growth Factor A Proteins 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
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 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
- 229910052799 carbon Inorganic materials 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000006166 lysate Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XNRFNVMAYPXUOY-UHFFFAOYSA-N 4-phenyl-1h-imidazole-5-carbaldehyde Chemical compound N1=CNC(C=2C=CC=CC=2)=C1C=O XNRFNVMAYPXUOY-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 102100034594 Angiopoietin-1 Human genes 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 6
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 6
- 101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 6
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 5
- 108010009906 Angiopoietins Proteins 0.000 description 5
- 102000009840 Angiopoietins Human genes 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 229920000136 polysorbate Polymers 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
- 235000002374 tyrosine Nutrition 0.000 description 5
- SPWBFAGJGSSFNS-MDZDMXLPSA-N 2,2-dimethyl-n-[4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-yl]propanamide Chemical compound CC(C)(C)C(=O)NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 SPWBFAGJGSSFNS-MDZDMXLPSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- SINQIEAULQKUPD-UHFFFAOYSA-N 4-[4-(6-methoxy-2-naphthalenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C=1N=C(C=2C=CC(=CC=2)S(C)=O)NC=1C1=CC=NC=C1 SINQIEAULQKUPD-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- VZDFUZNYSXFDFV-BQYQJAHWSA-N n-[4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-yl]acetamide Chemical compound CC(=O)NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 VZDFUZNYSXFDFV-BQYQJAHWSA-N 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011593 sulfur Chemical group 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 4
- UOAJQXSXVKVMQH-BENRWUELSA-N (z)-2-(2-aminopyrimidin-4-yl)-3-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)prop-2-enoic acid Chemical compound NC1=NC=CC(C(=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)\C(O)=O)=N1 UOAJQXSXVKVMQH-BENRWUELSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- CFAJUZYHRQDOHA-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)cyclohexan-1-amine Chemical compound C1CN(C)CCN1C1CCC(N)CC1 CFAJUZYHRQDOHA-UHFFFAOYSA-N 0.000 description 3
- XCPXVFWYOGYTRY-AATRIKPKSA-N 4-[(e)-2-[6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC(Cl)=CC=2)=N1 XCPXVFWYOGYTRY-AATRIKPKSA-N 0.000 description 3
- LVILGAOSPDLNRM-UHFFFAOYSA-N 4-methylpyrimidine Chemical compound CC1=CC=NC=N1 LVILGAOSPDLNRM-UHFFFAOYSA-N 0.000 description 3
- NKLACKSAXMBAAK-UHFFFAOYSA-N 5-ethynyl-1-methyl-4-phenylimidazole Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1C#C NKLACKSAXMBAAK-UHFFFAOYSA-N 0.000 description 3
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 3
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- 101150048336 Flt1 gene Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 208000007766 Kaposi sarcoma Diseases 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 206010025282 Lymphoedema Diseases 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010029260 Neuroblastoma Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 description 3
- 208000000453 Skin Neoplasms Diseases 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 description 3
- 206010057644 Testis cancer Diseases 0.000 description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000004037 angiogenesis inhibitor Substances 0.000 description 3
- 230000002491 angiogenic effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000007080 aromatic substitution reaction Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 108700010039 chimeric receptor Proteins 0.000 description 3
- 208000006990 cholangiocarcinoma Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 201000011066 hemangioma Diseases 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 208000002502 lymphedema Diseases 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 206010038038 rectal cancer Diseases 0.000 description 3
- 201000001275 rectum cancer Diseases 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 201000003120 testicular cancer Diseases 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 201000002510 thyroid cancer Diseases 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 201000005112 urinary bladder cancer Diseases 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- UOAITHNNKASUMP-UHFFFAOYSA-N 2,2-dimethyl-n-(4-methylpyrimidin-2-yl)propanamide Chemical compound CC1=CC=NC(NC(=O)C(C)(C)C)=N1 UOAITHNNKASUMP-UHFFFAOYSA-N 0.000 description 2
- KCKVSGKYAJCVQC-VOTSOKGWSA-N 2-[5-[(e)-2-(2-aminopyrimidin-4-yl)ethenyl]-4-phenylimidazol-1-yl]acetic acid Chemical compound NC1=NC=CC(\C=C\C=2N(C=NC=2C=2C=CC=CC=2)CC(O)=O)=N1 KCKVSGKYAJCVQC-VOTSOKGWSA-N 0.000 description 2
- XYVZNILJEWQOBC-VOTSOKGWSA-N 2-amino-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidine-5-carboxylic acid Chemical compound NC1=NC=C(C(O)=O)C(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 XYVZNILJEWQOBC-VOTSOKGWSA-N 0.000 description 2
- PCTWXPSIINTELJ-VAWYXSNFSA-N 2-amino-n-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidine-5-carboxamide Chemical compound C1CN(C)CCN1C1CCC(NC(=O)C=2C(=NC(N)=NC=2)\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)CC1 PCTWXPSIINTELJ-VAWYXSNFSA-N 0.000 description 2
- PKFJUPMFBJIAEA-UHFFFAOYSA-N 3-benzyl-5-phenylimidazole-4-carbaldehyde Chemical compound O=CC1=C(C=2C=CC=CC=2)N=CN1CC1=CC=CC=C1 PKFJUPMFBJIAEA-UHFFFAOYSA-N 0.000 description 2
- ZUZLMEAXVBJUSB-MDZDMXLPSA-N 4-[(e)-2-(2-phenylimidazo[1,2-a]pyridin-3-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3C=CC=CC3=NC=2C=2C=CC=CC=2)=N1 ZUZLMEAXVBJUSB-MDZDMXLPSA-N 0.000 description 2
- VHTDDEQGXAKILP-VAWYXSNFSA-N 4-[(e)-2-(3-benzyl-5-phenylimidazol-4-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N(C=NC=2C=2C=CC=CC=2)CC=2C=CC=CC=2)=N1 VHTDDEQGXAKILP-VAWYXSNFSA-N 0.000 description 2
- ZOBMEONPYSLCBL-BQYQJAHWSA-N 4-[(e)-2-(3-methyl-5-phenylimidazol-4-yl)ethenyl]pyrimidin-2-amine Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1\C=C\C1=CC=NC(N)=N1 ZOBMEONPYSLCBL-BQYQJAHWSA-N 0.000 description 2
- MACYCBPLOCRJMO-BQYQJAHWSA-N 4-[(e)-2-(3-methyl-5-phenylimidazol-4-yl)ethenyl]pyrimidine Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1\C=C\C1=CC=NC=N1 MACYCBPLOCRJMO-BQYQJAHWSA-N 0.000 description 2
- QIOXDSKORYYEHE-VOTSOKGWSA-N 4-[(e)-2-(4-phenyl-1h-imidazol-5-yl)ethenyl]pyridine Chemical compound N1C=NC(C=2C=CC=CC=2)=C1/C=C/C1=CC=NC=C1 QIOXDSKORYYEHE-VOTSOKGWSA-N 0.000 description 2
- ZBOJOJGUEBNBAS-VOTSOKGWSA-N 4-[(e)-2-(4-phenyl-1h-imidazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C2=C(N=CN2)C=2C=CC=CC=2)=N1 ZBOJOJGUEBNBAS-VOTSOKGWSA-N 0.000 description 2
- LZKJVSVZULTVSD-VOTSOKGWSA-N 4-[(e)-2-(4-phenyl-1h-imidazol-5-yl)ethenyl]pyrimidine Chemical compound N1C=NC(C=2C=CC=CC=2)=C1/C=C/C1=CC=NC=N1 LZKJVSVZULTVSD-VOTSOKGWSA-N 0.000 description 2
- GOJZHNWOESVAEU-VOTSOKGWSA-N 4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 GOJZHNWOESVAEU-VOTSOKGWSA-N 0.000 description 2
- AAGVCJFRSHQFKK-CMDGGOBGSA-N 4-[(e)-2-[5-phenyl-3-(2-pyrrolidin-1-ylethyl)imidazol-4-yl]ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N(C=NC=2C=2C=CC=CC=2)CCN2CCCC2)=N1 AAGVCJFRSHQFKK-CMDGGOBGSA-N 0.000 description 2
- LMCRVVCELABSST-AATRIKPKSA-N 4-[(e)-2-[6-(4-bromophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC(Br)=CC=2)=N1 LMCRVVCELABSST-AATRIKPKSA-N 0.000 description 2
- UEWOMQWOXKUUDE-AATRIKPKSA-N 4-[(e)-2-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC(F)=CC=2)=N1 UEWOMQWOXKUUDE-AATRIKPKSA-N 0.000 description 2
- HJRTWRFEWSHOGT-FPLPWBNLSA-N 4-[(z)-2-(3-methyl-5-phenylimidazol-4-yl)ethenyl]pyridine Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1\C=C/C1=CC=NC=C1 HJRTWRFEWSHOGT-FPLPWBNLSA-N 0.000 description 2
- QPSXGKIQDFDPPR-UHFFFAOYSA-N 4-[2-(3-methyl-5-phenylimidazol-4-yl)ethynyl]-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(C#CC=2N(C=NC=2C=2C=CC=CC=2)C)=N1 QPSXGKIQDFDPPR-UHFFFAOYSA-N 0.000 description 2
- CWGVBNKZWJKLKN-UHFFFAOYSA-N 4-[2-(3-methyl-5-phenylimidazol-4-yl)ethynyl]pyrimidine Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1C#CC1=CC=NC=N1 CWGVBNKZWJKLKN-UHFFFAOYSA-N 0.000 description 2
- AQVBHAYKMZDNHS-VOTSOKGWSA-N 4-[4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-yl]morpholine Chemical compound C1COCCN1C1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 AQVBHAYKMZDNHS-VOTSOKGWSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- XDADSGBUZWZQQQ-UHFFFAOYSA-N 4-bromopyrimidine Chemical compound BrC1=CC=NC=N1 XDADSGBUZWZQQQ-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- UGGNFNQPEKXYKQ-BQYQJAHWSA-N 4-methyl-6-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC(C)=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 UGGNFNQPEKXYKQ-BQYQJAHWSA-N 0.000 description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- LKFDHCVABDVLBF-VOTSOKGWSA-N 5-bromo-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=C(Br)C(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 LKFDHCVABDVLBF-VOTSOKGWSA-N 0.000 description 2
- UHBUCIIWPLRIRV-UHFFFAOYSA-N 5-phenyl-3-(2-pyrrolidin-1-ylethyl)imidazole-4-carbaldehyde Chemical compound O=CC1=C(C=2C=CC=CC=2)N=CN1CCN1CCCC1 UHBUCIIWPLRIRV-UHFFFAOYSA-N 0.000 description 2
- RLSLWFLVJBELPC-BQYQJAHWSA-N 6-[(e)-2-(3-methyl-5-phenylimidazol-4-yl)ethenyl]-1h-pyrimidin-2-one Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1\C=C\C1=CC=NC(O)=N1 RLSLWFLVJBELPC-BQYQJAHWSA-N 0.000 description 2
- VFGKNTSPPFUHHO-VOTSOKGWSA-N 6-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]-1h-pyrimidin-2-one Chemical compound OC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 VFGKNTSPPFUHHO-VOTSOKGWSA-N 0.000 description 2
- FIZQADVSPVFTQI-VOTSOKGWSA-N 6-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-4-amine Chemical compound C1=NC(N)=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 FIZQADVSPVFTQI-VOTSOKGWSA-N 0.000 description 2
- WUKSOWRQHCGODG-AATRIKPKSA-N 6-[(e)-2-[6-(4-bromophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]-1h-pyrimidin-2-one Chemical compound OC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC(Br)=CC=2)=N1 WUKSOWRQHCGODG-AATRIKPKSA-N 0.000 description 2
- CTCSNFQSCWSRHO-AATRIKPKSA-N 6-[(e)-2-[6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]-1h-pyrimidin-2-one Chemical compound OC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC(Cl)=CC=2)=N1 CTCSNFQSCWSRHO-AATRIKPKSA-N 0.000 description 2
- TVIFRVPVSSRLJK-AATRIKPKSA-N 6-[(e)-2-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]-1h-pyrimidin-2-one Chemical compound OC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC(F)=CC=2)=N1 TVIFRVPVSSRLJK-AATRIKPKSA-N 0.000 description 2
- MRJKXXDKYLGLRQ-VOTSOKGWSA-N 6-phenyl-5-[(e)-2-pyrimidin-4-ylethenyl]imidazo[2,1-b][1,3]thiazole Chemical compound C=1C=CC=CC=1C=1N=C2SC=CN2C=1/C=C/C1=CC=NC=N1 MRJKXXDKYLGLRQ-VOTSOKGWSA-N 0.000 description 2
- 208000037853 Abnormal uterine bleeding Diseases 0.000 description 2
- 208000030090 Acute Disease Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010051113 Arterial restenosis Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010004593 Bile duct cancer Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 201000009273 Endometriosis Diseases 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 101100372761 Mus musculus Flt1 gene Proteins 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 102000050000 TIE-1 Receptor Human genes 0.000 description 2
- 108010090089 TIE-1 Receptor Proteins 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 description 2
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 2
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 208000026900 bile duct neoplasm Diseases 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000000451 chemical ionisation Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 230000001687 destabilization Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 2
- SNQXMKUGEOWKDN-CMDGGOBGSA-N ethyl 2-amino-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)N=C1\C=C\C1=C(C=2C=CC=CC=2)N=C2N1C=CS2 SNQXMKUGEOWKDN-CMDGGOBGSA-N 0.000 description 2
- QVLJLWHOILVHJJ-UHFFFAOYSA-N ethyl 2-pyridin-4-ylacetate Chemical compound CCOC(=O)CC1=CC=NC=C1 QVLJLWHOILVHJJ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 238000005734 heterodimerization reaction Methods 0.000 description 2
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- QUKHTXIPNRAWKD-QBFSEMIESA-N methyl (z)-2-(2-aminopyrimidin-4-yl)-3-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)prop-2-enoate Chemical compound C=1C=NC(N)=NC=1/C(C(=O)OC)=C/C(N1C=CSC1=N1)=C1C1=CC=CC=C1 QUKHTXIPNRAWKD-QBFSEMIESA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- WKBACBJIPAQRKE-OUKQBFOZSA-N n-(1-phenylethyl)-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound C=1C=CC=CC=1C(C)NC(N=1)=NC=CC=1\C=C\C(N1C=CSC1=N1)=C1C1=CC=CC=C1 WKBACBJIPAQRKE-OUKQBFOZSA-N 0.000 description 2
- DMCLEULRLYNRNF-VAWYXSNFSA-N n-benzyl-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound C=1C=CC=CC=1CNC(N=1)=NC=CC=1\C=C\C(N1C=CSC1=N1)=C1C1=CC=CC=C1 DMCLEULRLYNRNF-VAWYXSNFSA-N 0.000 description 2
- DBJYPFDFNHRDNQ-BQYQJAHWSA-N n-methyl-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound CNC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=N1 DBJYPFDFNHRDNQ-BQYQJAHWSA-N 0.000 description 2
- LTKGFUQBPSYQKP-UHFFFAOYSA-N n-methyl-4-[2-(3-methyl-5-phenylimidazol-4-yl)ethynyl]pyrimidin-2-amine Chemical compound CNC1=NC=CC(C#CC=2N(C=NC=2C=2C=CC=CC=2)C)=N1 LTKGFUQBPSYQKP-UHFFFAOYSA-N 0.000 description 2
- BIZISPKHXAZMJW-VAWYXSNFSA-N n-phenyl-4-[(e)-2-(6-phenylimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound N=1C=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=CC=CC=2)=NC=1NC1=CC=CC=C1 BIZISPKHXAZMJW-VAWYXSNFSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 2
- 210000001210 retinal vessel Anatomy 0.000 description 2
- 102200134815 rs80338908 Human genes 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003457 sulfones Chemical group 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- CBLWZLUPKGQXJM-UHFFFAOYSA-N tert-butyl 2-(5-formyl-4-phenylimidazol-1-yl)acetate Chemical compound CC(C)(C)OC(=O)CN1C=NC(C=2C=CC=CC=2)=C1C=O CBLWZLUPKGQXJM-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 206010046766 uterine cancer Diseases 0.000 description 2
- 201000009371 venous hemangioma Diseases 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- YUHZIUAREWNXJT-UHFFFAOYSA-N (2-fluoropyridin-3-yl)boronic acid Chemical class OB(O)C1=CC=CN=C1F YUHZIUAREWNXJT-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- ISNKSXRJJVWFIL-UHFFFAOYSA-N (sulfonylamino)amine Chemical compound NN=S(=O)=O ISNKSXRJJVWFIL-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 1
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- LDKSCZJUIURGMW-UHFFFAOYSA-N 1-isothiocyanato-3-methylsulfanylpropane Chemical group CSCCCN=C=S LDKSCZJUIURGMW-UHFFFAOYSA-N 0.000 description 1
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
- 125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- BHAKRVSCGILCEW-UHFFFAOYSA-N 2-chloro-4-methylpyrimidine Chemical compound CC1=CC=NC(Cl)=N1 BHAKRVSCGILCEW-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- GDQWGRMPXASNTI-UHFFFAOYSA-N 2-phenyl-3-imidazo[1,2-a]pyridinecarboxaldehyde Chemical compound N1=C2C=CC=CN2C(C=O)=C1C1=CC=CC=C1 GDQWGRMPXASNTI-UHFFFAOYSA-N 0.000 description 1
- CPVZWLSLJTZDLG-UHFFFAOYSA-N 2-phenylimidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound C=1N2C(C=O)=CN=C2SC=1C1=CC=CC=C1 CPVZWLSLJTZDLG-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- IITIZHOBOIBGBW-UHFFFAOYSA-N 3-ethyl-2h-1,3-benzothiazole Chemical compound C1=CC=C2N(CC)CSC2=C1 IITIZHOBOIBGBW-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- JDFDHBSESGTDAL-UHFFFAOYSA-N 3-methoxypropan-1-ol Chemical compound COCCCO JDFDHBSESGTDAL-UHFFFAOYSA-N 0.000 description 1
- ZJAUGESKXZRDFD-UHFFFAOYSA-N 3-pyrimidin-2-ylpropanamide Chemical compound NC(=O)CCC1=NC=CC=N1 ZJAUGESKXZRDFD-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- PWKMWUOCPKAFMY-VOTSOKGWSA-N 4-[(e)-2-(6-phenyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3CCSC3=NC=2C=2C=CC=CC=2)=N1 PWKMWUOCPKAFMY-VOTSOKGWSA-N 0.000 description 1
- INKHRJGUKLYOTL-SNAWJCMRSA-N 4-[(e)-2-[6-[3-(trifluoromethyl)phenyl]imidazo[2,1-b][1,3]thiazol-5-yl]ethenyl]pyrimidin-2-amine Chemical compound NC1=NC=CC(\C=C\C=2N3C=CSC3=NC=2C=2C=C(C=CC=2)C(F)(F)F)=N1 INKHRJGUKLYOTL-SNAWJCMRSA-N 0.000 description 1
- ANGLKXPVSGRNCL-UHFFFAOYSA-N 4-[2-(3-methyl-5-phenylimidazol-4-yl)ethynyl]-2-methylsulfinylpyrimidine Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1C#CC1=CC=NC(S(C)=O)=N1 ANGLKXPVSGRNCL-UHFFFAOYSA-N 0.000 description 1
- XWPNKFIQBDGGIM-UHFFFAOYSA-N 4-[2-(3-methyl-5-phenylimidazol-4-yl)ethynyl]-2-methylsulfonylpyrimidine Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1C#CC1=CC=NC(S(C)(=O)=O)=N1 XWPNKFIQBDGGIM-UHFFFAOYSA-N 0.000 description 1
- SECBGKYJKCNDID-UHFFFAOYSA-N 4-iodo-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(I)=N1 SECBGKYJKCNDID-UHFFFAOYSA-N 0.000 description 1
- LPQVTZJEIXYDQA-UHFFFAOYSA-N 5-bromo-4-methylpyrimidin-2-amine Chemical compound CC1=NC(N)=NC=C1Br LPQVTZJEIXYDQA-UHFFFAOYSA-N 0.000 description 1
- DERSRCNYCMEQSR-UHFFFAOYSA-N 6-(4-bromophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound C1=CC(Br)=CC=C1C1=C(C=O)N2C=CSC2=N1 DERSRCNYCMEQSR-UHFFFAOYSA-N 0.000 description 1
- DDZYUQDDVHXBIQ-UHFFFAOYSA-N 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound C1=CC(Cl)=CC=C1C1=C(C=O)N2C=CSC2=N1 DDZYUQDDVHXBIQ-UHFFFAOYSA-N 0.000 description 1
- NMJLTWCGJYJVDO-UHFFFAOYSA-N 6-(4-fluorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound C1=CC(F)=CC=C1C1=C(C=O)N2C=CSC2=N1 NMJLTWCGJYJVDO-UHFFFAOYSA-N 0.000 description 1
- WKUMQNBIHNLYFF-UHFFFAOYSA-N 6-[3-(trifluoromethyl)phenyl]imidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound FC(F)(F)C1=CC=CC(C2=C(N3C=CSC3=N2)C=O)=C1 WKUMQNBIHNLYFF-UHFFFAOYSA-N 0.000 description 1
- AHHHDTLXONDKQF-UHFFFAOYSA-N 6-methyl-1h-pyrimidin-2-one Chemical compound CC1=CC=NC(O)=N1 AHHHDTLXONDKQF-UHFFFAOYSA-N 0.000 description 1
- LAERIBHKDNBVOO-UHFFFAOYSA-N 6-methylpyrimidin-4-amine Chemical compound CC1=CC(N)=NC=N1 LAERIBHKDNBVOO-UHFFFAOYSA-N 0.000 description 1
- XOGXXJXDZCAAPL-UHFFFAOYSA-N 6-phenyl-2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-carbaldehyde Chemical compound N1=C2SCCN2C(C=O)=C1C1=CC=CC=C1 XOGXXJXDZCAAPL-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010048154 Angiopoietin-1 Proteins 0.000 description 1
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 1
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 0.000 description 1
- 108700020462 BRCA2 Proteins 0.000 description 1
- 206010004950 Birth mark Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101150008921 Brca2 gene Proteins 0.000 description 1
- 108010037003 Buserelin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical group [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000000311 Cytosine Deaminase Human genes 0.000 description 1
- 108010080611 Cytosine Deaminase Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 101150009958 FLT4 gene Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 description 1
- 108700041567 MDR Genes Proteins 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100323232 Mus musculus Ang3 gene Proteins 0.000 description 1
- 101100216078 Mus musculus Ang4 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- XOTCXWQAPVALFW-UHFFFAOYSA-N N,N-dimethylacetamide N-methylmethanamine Chemical compound C(C)(=O)N(C)C.CNC XOTCXWQAPVALFW-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 102000005450 TIE receptors Human genes 0.000 description 1
- 108010006830 TIE receptors Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108010042352 Urokinase Plasminogen Activator Receptors Chemical group 0.000 description 1
- 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 208000032594 Vascular Remodeling Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 125000004018 acid anhydride group Chemical group 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ZPNFWUPYTFPOJU-MPSLMFKFSA-N aprotinin Chemical compound CC[C@H](C)[C@@H]1NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CSSC[C@H]3NC(=O)CNC(=O)CNC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CSSC[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc4ccccc4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC3=O)C(=O)N[C@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](CSSC[C@@H](NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H]3CCCN3C(=O)[C@H](N)CCCNC(N)=N)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N3CCC[C@@H]3C(=O)N3CCC[C@H]3C(=O)N[C@H](Cc3ccc(O)cc3)C(=O)N[C@H]([C@H](C)O)C(=O)NCC(=O)N3CCC[C@H]3C(=O)N2)C(=O)NCC(=O)NCC(=O)N[C@H](C)C(O)=O)NC(=O)[C@@H](CC(C)C)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](NC1=O)[C@H](C)CC)[C@@H](C)O)C(C)C ZPNFWUPYTFPOJU-MPSLMFKFSA-N 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 1
- 229960002719 buserelin Drugs 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229950002826 canertinib Drugs 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
- JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- YBFVMJRSZCVJJP-UHFFFAOYSA-N ethyl 2-amino-4-methylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)N=C1C YBFVMJRSZCVJJP-UHFFFAOYSA-N 0.000 description 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 125000006351 ethylthiomethyl group Chemical group [H]C([H])([H])C([H])([H])SC([H])([H])* 0.000 description 1
- 125000005290 ethynyloxy group Chemical group C(#C)O* 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- FDRYQDWXFZBBAD-UHFFFAOYSA-N hydron;6-methyl-1h-pyrimidin-2-one;chloride Chemical compound Cl.CC1=CC=NC(=O)N1 FDRYQDWXFZBBAD-UHFFFAOYSA-N 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical group CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
- 229950008959 marimastat Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- UHHWQUBWFZALOK-BQYQJAHWSA-N n-[4-[(e)-2-(6-phenyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl)ethenyl]pyrimidin-2-yl]acetamide Chemical compound CC(=O)NC1=NC=CC(\C=C\C=2N3CCSC3=NC=2C=2C=CC=CC=2)=N1 UHHWQUBWFZALOK-BQYQJAHWSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000011581 secondary neoplasm Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
- WYVFPGFWUKBXPZ-UHFFFAOYSA-N tert-butyl n-(4-oxocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(=O)CC1 WYVFPGFWUKBXPZ-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 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
- 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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 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
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 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
- 230000003827 upregulation Effects 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
- 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)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (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 |
|---|---|---|---|
| GB0230089.5 | 2002-12-24 | ||
| GBGB0230089.5A GB0230089D0 (en) | 2002-12-24 | 2002-12-24 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20050087852A true KR20050087852A (ko) | 2005-08-31 |
Family
ID=9950374
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057011870A Withdrawn KR20050087852A (ko) | 2002-12-24 | 2003-12-19 | 치료제 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20060069109A1 (https=) |
| EP (1) | EP1575963B1 (https=) |
| JP (1) | JP2006515593A (https=) |
| KR (1) | KR20050087852A (https=) |
| CN (1) | CN1751052A (https=) |
| AT (1) | ATE394403T1 (https=) |
| AU (1) | AU2003295135A1 (https=) |
| BR (1) | BR0317708A (https=) |
| CA (1) | CA2508917A1 (https=) |
| DE (1) | DE60320849D1 (https=) |
| ES (1) | ES2305548T3 (https=) |
| GB (1) | GB0230089D0 (https=) |
| MX (1) | MXPA05006921A (https=) |
| NO (1) | NO20052989L (https=) |
| WO (1) | WO2004058776A1 (https=) |
| ZA (1) | ZA200504827B (https=) |
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 |
| AU2015210454B2 (en) * | 2005-12-23 | 2016-10-27 | Takeda Pharmaceuticals U.S.A., Inc. | Bicyclic heteroaryl compounds |
| SI1973545T1 (sl) * | 2005-12-23 | 2013-04-30 | Ariad Pharmaceuticals, Inc. | Spojine bicikličnega heteroarila |
| EA034598B1 (ru) | 2005-12-23 | 2020-02-25 | Ариад Фармасьютикалз, Инк. | Применение бициклических гетероарильных соединений для лечения рака |
| US8278307B2 (en) | 2006-05-08 | 2012-10-02 | Ariad Pharmaceuticals, Inc. | Monocyclic Heteroaryl compounds |
| CN103435595A (zh) | 2006-05-08 | 2013-12-11 | 阿里亚德医药股份有限公司 | 炔类杂芳基化合物 |
| WO2008076883A2 (en) | 2006-12-15 | 2008-06-26 | Abraxis Bioscience, Inc. | Triazine derivatives and their therapeutical applications |
| EP2307456B1 (en) | 2008-06-27 | 2014-10-15 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| CA2743449C (en) | 2008-11-12 | 2016-10-18 | Ariad Pharmaceuticals, Inc. | Pyrazinopyrazines and derivatives as kinase inhibitors |
| JP5785940B2 (ja) | 2009-06-09 | 2015-09-30 | アブラクシス バイオサイエンス， エルエルシー | トリアジン誘導体類及びそれらの治療応用 |
| EP2440053A4 (en) | 2009-06-09 | 2012-10-31 | California Capital Equity Llc | BENZYL SUBSTITUTED TRIAZINE DERIVATIVES AND THERAPEUTIC APPLICATIONS THEREOF |
| 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 |
| MX2014014308A (es) * | 2012-05-30 | 2015-02-12 | Hoffmann La Roche | Pirrolidino heterociclos. |
| CA3022250A1 (en) | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| US12570660B2 (en) | 2019-08-16 | 2026-03-10 | Cyclacel Pharmaceuticals, Inc | Process for the preparation of a pyrimidino-diazepine derivative |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003509428A (ja) * | 1999-09-17 | 2003-03-11 | アボツト・ゲー・エム・ベー・ハー・ウント・コンパニー・カーゲー | 治療薬としてのピラゾロピリミジン |
| AU1529901A (en) * | 1999-11-22 | 2001-06-04 | Smithkline Beecham Plc | Compounds |
| ATE365730T1 (de) * | 2000-11-20 | 2007-07-15 | Smithkline Beecham Corp | Neuartige verbindungen |
| 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 CN CNA2003801098327A patent/CN1751052A/zh active Pending
- 2003-12-19 EP EP03786136A patent/EP1575963B1/en not_active Expired - Lifetime
- 2003-12-19 BR BR0317708-4A patent/BR0317708A/pt not_active Application Discontinuation
- 2003-12-19 MX MXPA05006921A patent/MXPA05006921A/es unknown
- 2003-12-19 JP JP2004563345A patent/JP2006515593A/ja active Pending
- 2003-12-19 AU AU2003295135A patent/AU2003295135A1/en not_active Abandoned
- 2003-12-19 US US10/540,348 patent/US20060069109A1/en not_active Abandoned
- 2003-12-19 DE DE60320849T patent/DE60320849D1/de not_active Expired - Fee Related
- 2003-12-19 KR KR1020057011870A patent/KR20050087852A/ko not_active Withdrawn
- 2003-12-19 AT AT03786136T patent/ATE394403T1/de not_active IP Right Cessation
- 2003-12-19 CA CA002508917A patent/CA2508917A1/en not_active Abandoned
- 2003-12-19 WO PCT/GB2003/005568 patent/WO2004058776A1/en not_active Ceased
- 2003-12-19 ES ES03786136T patent/ES2305548T3/es not_active Expired - Lifetime
-
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 |
|---|---|
| MXPA05006921A (es) | 2005-08-18 |
| US20060069109A1 (en) | 2006-03-30 |
| CA2508917A1 (en) | 2004-07-15 |
| ES2305548T3 (es) | 2008-11-01 |
| NO20052989D0 (no) | 2005-06-17 |
| WO2004058776A1 (en) | 2004-07-15 |
| JP2006515593A (ja) | 2006-06-01 |
| DE60320849D1 (de) | 2008-06-19 |
| GB0230089D0 (en) | 2003-01-29 |
| EP1575963A1 (en) | 2005-09-21 |
| BR0317708A (pt) | 2005-11-22 |
| EP1575963B1 (en) | 2008-05-07 |
| AU2003295135A1 (en) | 2004-07-22 |
| ZA200504827B (en) | 2006-04-26 |
| NO20052989L (no) | 2005-07-21 |
| ATE394403T1 (de) | 2008-05-15 |
| CN1751052A (zh) | 2006-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7427616B2 (en) | Condensed pyridines and pyrimidines with tie2 (TEK) activity | |
| US20080027076A1 (en) | Pyrimidines With Tie2 (Tek) Activity | |
| KR20050087852A (ko) | 치료제 | |
| JP2008535780A (ja) | 化合物 | |
| US20080194552A1 (en) | Aminopyrimidine Derivatives With Tie2 Inhibiting Activity | |
| EA018708B1 (ru) | ПРОИЗВОДНЫЕ МОРФОЛИНОПИРИМИДИНА, ИСПОЛЬЗУЕМЫЕ ПРИ ЗАБОЛЕВАНИЯХ, СВЯЗАННЫХ С mTOR КИНАЗОЙ И/ИЛИ PI3K | |
| WO2014106800A2 (en) | Substituted 2-amino pyrimidine derivatives as kinase inhibitors | |
| US20080108608A1 (en) | Pyrimidines With Tie2 (Tek) Activity | |
| US20080146599A1 (en) | Pyrimidine Compounds Having Tie-2 (Tek) Inhibitory Activity | |
| JP2008528663A (ja) | Ｔｉｅｓ（ＴＥＫ）阻害活性を有するピリミジン化合物 | |
| US7476677B2 (en) | Substituted thieno- and thiazolo- [2,3-d]pyrimidines and [2,3-c]pyridines as inhibitors of Tie2 | |
| CN101151261A (zh) | 具有tie2（tek）抑制活性的嘧啶化合物 | |
| CN101137652A (zh) | 具有tie2（tek）抑制活性的嘧啶化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20050623 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |