JP2007515400A - タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 - Google Patents
タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 Download PDFInfo
- Publication number
- JP2007515400A JP2007515400A JP2006540401A JP2006540401A JP2007515400A JP 2007515400 A JP2007515400 A JP 2007515400A JP 2006540401 A JP2006540401 A JP 2006540401A JP 2006540401 A JP2006540401 A JP 2006540401A JP 2007515400 A JP2007515400 A JP 2007515400A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- trifluoromethyl
- mmol
- pyrimidin
- yloxy
- 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.)
- Ceased
Links
- 201000010099 disease Diseases 0.000 title claims abstract description 92
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 92
- 230000001419 dependent effect Effects 0.000 title claims abstract description 69
- 102000001253 Protein Kinase Human genes 0.000 title claims abstract description 33
- 108060006633 protein kinase Proteins 0.000 title claims abstract description 33
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 55
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 37
- 238000002360 preparation method Methods 0.000 claims abstract description 23
- 241001465754 Metazoa Species 0.000 claims abstract description 16
- 230000002062 proliferating effect Effects 0.000 claims abstract description 15
- OBHVFBJZHBSDOF-UHFFFAOYSA-N 1-phenyl-3-(4-pyrimidin-4-yloxyphenyl)urea Chemical class C=1C=C(OC=2N=CN=CC=2)C=CC=1NC(=O)NC1=CC=CC=C1 OBHVFBJZHBSDOF-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 397
- -1 Pyrimidin-4-yloxy Chemical group 0.000 claims description 261
- 229910052739 hydrogen Inorganic materials 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 97
- 229910052757 nitrogen Inorganic materials 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 230000005764 inhibitory process Effects 0.000 claims description 29
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims description 27
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 26
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 241000282412 Homo Species 0.000 claims description 6
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 201000002510 thyroid cancer Diseases 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 238000001890 transfection Methods 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 354
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 203
- 239000000243 solution Substances 0.000 description 124
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 119
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 116
- 235000019439 ethyl acetate Nutrition 0.000 description 101
- 238000005160 1H NMR spectroscopy Methods 0.000 description 87
- 210000004027 cell Anatomy 0.000 description 77
- 238000004128 high performance liquid chromatography Methods 0.000 description 76
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 61
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- 229910004298 SiO 2 Inorganic materials 0.000 description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 57
- 125000003545 alkoxy group Chemical group 0.000 description 56
- 239000011541 reaction mixture Substances 0.000 description 56
- 235000002639 sodium chloride Nutrition 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- 239000011734 sodium Substances 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 239000004202 carbamide Substances 0.000 description 46
- 239000000203 mixture Substances 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 230000000694 effects Effects 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 45
- 238000003756 stirring Methods 0.000 description 45
- 108090000623 proteins and genes Proteins 0.000 description 43
- 230000002829 reductive effect Effects 0.000 description 42
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- 102000004169 proteins and genes Human genes 0.000 description 39
- 239000003921 oil Substances 0.000 description 36
- 235000019198 oils Nutrition 0.000 description 36
- 239000007787 solid Substances 0.000 description 34
- 239000007858 starting material Substances 0.000 description 34
- 125000000714 pyrimidinyl group Chemical group 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000012299 nitrogen atmosphere Substances 0.000 description 30
- 239000010410 layer Substances 0.000 description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
- 125000003282 alkyl amino group Chemical group 0.000 description 27
- 238000000034 method Methods 0.000 description 26
- JBULWLQCOPIREC-UHFFFAOYSA-N 4-chloro-6-(4-isocyanatophenoxy)pyrimidine Chemical compound C1=NC(Cl)=CC(OC=2C=CC(=CC=2)N=C=O)=N1 JBULWLQCOPIREC-UHFFFAOYSA-N 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 24
- 238000003818 flash chromatography Methods 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 125000005843 halogen group Chemical group 0.000 description 23
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 108091000080 Phosphotransferase Proteins 0.000 description 20
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 20
- 102000020233 phosphotransferase Human genes 0.000 description 20
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 19
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 19
- 238000004458 analytical method Methods 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 125000001309 chloro group Chemical group Cl* 0.000 description 18
- 239000012043 crude product Substances 0.000 description 18
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 18
- 150000003254 radicals Chemical class 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
- 229910052799 carbon Inorganic materials 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 208000032839 leukemia Diseases 0.000 description 16
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 241000700605 Viruses Species 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 239000012528 membrane Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 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 13
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 13
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 13
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 230000001028 anti-proliverative effect Effects 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 125000004076 pyridyl group Chemical group 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
- 241000701447 unidentified baculovirus Species 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 125000001246 bromo group Chemical group Br* 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 8
- 239000007868 Raney catalyst Substances 0.000 description 8
- 229910000564 Raney nickel Inorganic materials 0.000 description 8
- 108091008605 VEGF receptors Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 125000005936 piperidyl group Chemical group 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 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 7
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 102000001332 SRC Human genes 0.000 description 7
- 108060006706 SRC Proteins 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- VFBLMSPJYJOLGY-UHFFFAOYSA-N 4-(6-chloropyrimidin-4-yl)oxyaniline Chemical compound C1=CC(N)=CC=C1OC1=CC(Cl)=NC=N1 VFBLMSPJYJOLGY-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 239000002033 PVDF binder Substances 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 108020005202 Viral DNA Proteins 0.000 description 6
- ULHRKLSNHXXJLO-UHFFFAOYSA-L Yo-Pro-1 Chemical compound [I-].[I-].C1=CC=C2C(C=C3N(C4=CC=CC=C4O3)C)=CC=[N+](CCC[N+](C)(C)C)C2=C1 ULHRKLSNHXXJLO-UHFFFAOYSA-L 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 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 6
- 229940011871 estrogen Drugs 0.000 description 6
- 239000000262 estrogen Substances 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 6
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 6
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 6
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 5
- YXLLDVNFADYJEI-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(trifluoromethyl)aniline Chemical compound CN(C)CC1=CC=C(N)C=C1C(F)(F)F YXLLDVNFADYJEI-UHFFFAOYSA-N 0.000 description 5
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 5
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 5
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 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 5
- 125000005236 alkanoylamino group Chemical group 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 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 5
- 230000001086 cytosolic effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- HQHBGSMMAFAOHD-UHFFFAOYSA-N n-[4-(4-aminophenoxy)pyrimidin-2-yl]-n',n'-dimethylbutane-1,4-diamine Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=CC(N)=CC=2)=N1 HQHBGSMMAFAOHD-UHFFFAOYSA-N 0.000 description 5
- VAOMDCLCUPLVHF-UHFFFAOYSA-N n-[4-[4-amino-3-(trifluoromethyl)phenoxy]pyrimidin-2-yl]-n',n'-dimethylbutane-1,4-diamine Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C(N)=CC=2)C(F)(F)F)=N1 VAOMDCLCUPLVHF-UHFFFAOYSA-N 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 238000012746 preparative thin layer chromatography Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 125000005505 thiomorpholino group Chemical group 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 4
- SVFZOGUHNLYZIL-UHFFFAOYSA-N 2-chloro-4-(4-nitrophenoxy)pyrimidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=NC(Cl)=N1 SVFZOGUHNLYZIL-UHFFFAOYSA-N 0.000 description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
- ODCLHXGXGFBBTA-UHFFFAOYSA-N 3-nitro-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 ODCLHXGXGFBBTA-UHFFFAOYSA-N 0.000 description 4
- ZMWAZMYBMAAMAW-UHFFFAOYSA-N 4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)aniline Chemical compound C1CN(C)CCN1CC1=CC=C(N)C=C1C(F)(F)F ZMWAZMYBMAAMAW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229920001817 Agar Polymers 0.000 description 4
- 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 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 108091008794 FGF receptors Proteins 0.000 description 4
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 4
- 108010069236 Goserelin Proteins 0.000 description 4
- 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 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 102000029749 Microtubule Human genes 0.000 description 4
- 108091022875 Microtubule Proteins 0.000 description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 108091008606 PDGF receptors Proteins 0.000 description 4
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 4
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 4
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 4
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 4
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 4
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000001475 halogen functional group Chemical group 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 238000012417 linear regression Methods 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 210000004688 microtubule Anatomy 0.000 description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- GCIWCAMQJPRDKH-UHFFFAOYSA-N n-[4-(bromomethyl)-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound FC(F)(F)C(=O)NC1=CC=C(CBr)C(C(F)(F)F)=C1 GCIWCAMQJPRDKH-UHFFFAOYSA-N 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 102000016914 ras Proteins Human genes 0.000 description 4
- 108010014186 ras Proteins Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 125000000547 substituted alkyl group Chemical group 0.000 description 4
- 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 4
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 4
- USKQYZHWJZDNCM-UHFFFAOYSA-N tributyl-(6-methylpyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC(C)=N1 USKQYZHWJZDNCM-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- HREPGOPESZYNOL-UHFFFAOYSA-N 1-[4-(3-chlorophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-methylphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C)C(NC(=O)NC=3C=C(C(C=4C=C(Cl)C=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 HREPGOPESZYNOL-UHFFFAOYSA-N 0.000 description 3
- OSJLIVMHMNBALU-UHFFFAOYSA-N 1-[4-bromo-3-(trifluoromethyl)phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C1=C(Br)C(C(F)(F)F)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=C1 OSJLIVMHMNBALU-UHFFFAOYSA-N 0.000 description 3
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 3
- 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 3
- YDCZDHZFURASCQ-UHFFFAOYSA-N 4-(2-chloropyrimidin-4-yl)oxyaniline Chemical compound C1=CC(N)=CC=C1OC1=CC=NC(Cl)=N1 YDCZDHZFURASCQ-UHFFFAOYSA-N 0.000 description 3
- SNMPBYDKCDJQOY-UHFFFAOYSA-N 4-(4-aminophenoxy)pyrimidin-2-amine Chemical compound C1=CC(N)=CC=C1OC1=CC=NC(N)=N1 SNMPBYDKCDJQOY-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 3
- IBMDIOHUTCTSRK-UHFFFAOYSA-N 6-(4-aminophenoxy)-n-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]pyrimidin-4-amine Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1NC1=CC(OC=2C=CC(N)=CC=2)=NC=N1 IBMDIOHUTCTSRK-UHFFFAOYSA-N 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 3
- 229910002012 Aerosil® Inorganic materials 0.000 description 3
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical class [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 101100342473 Drosophila melanogaster Raf gene Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 3
- 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 3
- 101000974343 Homo sapiens Nuclear receptor coactivator 4 Proteins 0.000 description 3
- 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 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 3
- 208000006876 Multiple Endocrine Neoplasia Type 2b Diseases 0.000 description 3
- 206010073148 Multiple endocrine neoplasia type 2A Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
- 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 3
- 102100022927 Nuclear receptor coactivator 4 Human genes 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 3
- 102000052575 Proto-Oncogene Human genes 0.000 description 3
- 108700020978 Proto-Oncogene Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 101100523543 Rattus norvegicus Raf1 gene Proteins 0.000 description 3
- 208000007660 Residual Neoplasm Diseases 0.000 description 3
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 101100523549 Xenopus laevis raf1 gene Proteins 0.000 description 3
- 101150037250 Zhx2 gene Proteins 0.000 description 3
- VPZSTVPVDGHXIR-UHFFFAOYSA-N [3-amino-5-(trifluoromethyl)phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC(N)=CC(C(F)(F)F)=C1 VPZSTVPVDGHXIR-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000006323 alkenyl amino group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 229960003437 aminoglutethimide Drugs 0.000 description 3
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000001772 anti-angiogenic effect Effects 0.000 description 3
- 239000003886 aromatase inhibitor Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 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 3
- YCOSVOOIWSRISI-UHFFFAOYSA-N benzoyl 4-[[4-(carbamoylamino)-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound C(C1=CC=CC=C1)(=O)OC(=O)N1CCN(CC1)CC1=C(C=C(C=C1)NC(N)=O)C(F)(F)F YCOSVOOIWSRISI-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229960004562 carboplatin Drugs 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 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
- 239000012230 colorless oil Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229960005420 etoposide Drugs 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 229960000908 idarubicin Drugs 0.000 description 3
- 229960001101 ifosfamide Drugs 0.000 description 3
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 3
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000001301 oxygen Chemical group 0.000 description 3
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 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 3
- 229960001278 teniposide Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 3
- 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 3
- GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000003612 virological effect Effects 0.000 description 3
- 229910052727 yttrium Inorganic materials 0.000 description 3
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 3
- AADVCYNFEREWOS-UHFFFAOYSA-N (+)-DDM Natural products C=CC=CC(C)C(OC(N)=O)C(C)C(O)C(C)CC(C)=CC(C)C(O)C(C)C=CC(O)CC1OC(=O)C(C)C(O)C1C AADVCYNFEREWOS-UHFFFAOYSA-N 0.000 description 2
- GJAQOTDQHKDYRP-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-(2-methyl-4-nitrophenyl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1C GJAQOTDQHKDYRP-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- IVZPKZPPIFMMFS-UHFFFAOYSA-N 1-(2,2-dimethylpropyl)-4-[4-nitro-2-(trifluoromethyl)phenyl]piperazine Chemical compound C1CN(CC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1C(F)(F)F IVZPKZPPIFMMFS-UHFFFAOYSA-N 0.000 description 2
- RJCGHEJLLRULGF-UHFFFAOYSA-N 1-(2,2-dimethylpropyl)piperazine;dihydrobromide Chemical compound Br.Br.CC(C)(C)CN1CCNCC1 RJCGHEJLLRULGF-UHFFFAOYSA-N 0.000 description 2
- CLUBRSZMLYRTIP-UHFFFAOYSA-N 1-(4-ethylpiperazin-1-yl)-2-[4-nitro-2-(trifluoromethyl)phenyl]ethanone Chemical compound C1CN(CC)CCN1C(=O)CC1=CC=C([N+]([O-])=O)C=C1C(F)(F)F CLUBRSZMLYRTIP-UHFFFAOYSA-N 0.000 description 2
- HQJMOTPSEHISAV-UHFFFAOYSA-N 1-[3-(azetidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]-3-[4-(6-azidopyrimidin-4-yl)oxyphenyl]urea Chemical compound C=1C(NC(=O)NC=2C=CC(OC=3N=CN=C(N=[N+]=[N-])C=3)=CC=2)=CC(C(F)(F)F)=CC=1CN1CCC1 HQJMOTPSEHISAV-UHFFFAOYSA-N 0.000 description 2
- COBQRDMNZUGYMQ-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxyphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=CC(Cl)=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 COBQRDMNZUGYMQ-UHFFFAOYSA-N 0.000 description 2
- PEHMIVVTLCVIRH-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[3-[(4-propan-2-ylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC1=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N)C=3)=CC=2)=CC(C(F)(F)F)=C1 PEHMIVVTLCVIRH-UHFFFAOYSA-N 0.000 description 2
- ZTCSOKDGJGUELI-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[4-bromo-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Br)=CC=3)C(F)(F)F)=CC=2)=N1 ZTCSOKDGJGUELI-UHFFFAOYSA-N 0.000 description 2
- ONKPEZSAINHZEX-UHFFFAOYSA-N 1-[4-(6-azidopyrimidin-4-yl)oxyphenyl]-3-[3-(diethylaminomethyl)-5-(trifluoromethyl)phenyl]urea Chemical compound FC(F)(F)C1=CC(CN(CC)CC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N=[N+]=[N-])C=3)=CC=2)=C1 ONKPEZSAINHZEX-UHFFFAOYSA-N 0.000 description 2
- WNAJAGNSOLOFBL-UHFFFAOYSA-N 1-[4-(6-azidopyrimidin-4-yl)oxyphenyl]-3-[4-bromo-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(Br)C(C(F)(F)F)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N=[N+]=[N-])C=3)=CC=2)=C1 WNAJAGNSOLOFBL-UHFFFAOYSA-N 0.000 description 2
- HHXYWQPBFVPXEA-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-morpholin-4-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C=1C=C(N2CCOCC2)C(C(F)(F)F)=CC=1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 HHXYWQPBFVPXEA-UHFFFAOYSA-N 0.000 description 2
- OWWDWVJMZFYWPW-UHFFFAOYSA-N 1-[4-bromo-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Br)=CC=3)C(F)(F)F)=CC=2)=N1 OWWDWVJMZFYWPW-UHFFFAOYSA-N 0.000 description 2
- XUEASANJTFMBLN-UHFFFAOYSA-N 1-[4-nitro-2-(trifluoromethyl)phenyl]-4-piperidin-1-ylpiperidine Chemical group FC(F)(F)C1=CC([N+](=O)[O-])=CC=C1N1CCC(N2CCCCC2)CC1 XUEASANJTFMBLN-UHFFFAOYSA-N 0.000 description 2
- SXEQQBBOAMHOID-UHFFFAOYSA-N 1-bromo-4-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C(C(F)(F)F)=C1 SXEQQBBOAMHOID-UHFFFAOYSA-N 0.000 description 2
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 2
- XBYVYOUNELVKCX-UHFFFAOYSA-N 1-methyl-4-[4-nitro-2-(trifluoromethyl)phenoxy]piperidine Chemical compound C1CN(C)CCC1OC1=CC=C([N+]([O-])=O)C=C1C(F)(F)F XBYVYOUNELVKCX-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
- KDKDXLSKCGBKGQ-UHFFFAOYSA-N 2-chloro-4-(3-methyl-4-nitrophenoxy)pyrimidine Chemical compound C1=C([N+]([O-])=O)C(C)=CC(OC=2N=C(Cl)N=CC=2)=C1 KDKDXLSKCGBKGQ-UHFFFAOYSA-N 0.000 description 2
- SHYJABBRLIUSIS-UHFFFAOYSA-N 2-chloro-4-[4-nitro-3-(trifluoromethyl)phenoxy]pyrimidine Chemical compound C1=C(C(F)(F)F)C([N+](=O)[O-])=CC=C1OC1=CC=NC(Cl)=N1 SHYJABBRLIUSIS-UHFFFAOYSA-N 0.000 description 2
- XXXOBNJIIZQSPT-UHFFFAOYSA-N 2-methyl-4-nitrobenzoic acid Chemical compound CC1=CC([N+]([O-])=O)=CC=C1C(O)=O XXXOBNJIIZQSPT-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- NGHSTLBWWFFHMQ-UHFFFAOYSA-N 3-(6-methylpyridin-2-yl)-5-(trifluoromethyl)aniline Chemical compound CC1=CC=CC(C=2C=C(C=C(N)C=2)C(F)(F)F)=N1 NGHSTLBWWFFHMQ-UHFFFAOYSA-N 0.000 description 2
- NFBQFRVJXFZLQP-UHFFFAOYSA-N 3-(azetidin-1-ylmethyl)-5-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC(CN2CCC2)=C1 NFBQFRVJXFZLQP-UHFFFAOYSA-N 0.000 description 2
- DYBVNOUCRJYHCQ-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)aniline Chemical compound C1CN(C)CCN1CC1=CC(N)=CC(C(F)(F)F)=C1 DYBVNOUCRJYHCQ-UHFFFAOYSA-N 0.000 description 2
- IDDURSHAWBUWKF-UHFFFAOYSA-N 3-[(4-propan-2-ylpiperazin-1-yl)methyl]-5-(trifluoromethyl)aniline Chemical compound C1CN(C(C)C)CCN1CC1=CC(N)=CC(C(F)(F)F)=C1 IDDURSHAWBUWKF-UHFFFAOYSA-N 0.000 description 2
- NJGURZDSOJMPKQ-UHFFFAOYSA-N 3-[2-(2,2-dimethylpropylamino)ethyl]-1,3-oxazolidin-2-one Chemical compound CC(C)(C)CNCCN1CCOC1=O NJGURZDSOJMPKQ-UHFFFAOYSA-N 0.000 description 2
- YQVMOFXECVKZFY-UHFFFAOYSA-N 3-[[4-(6-azidopyrimidin-4-yl)oxyphenyl]carbamoylamino]-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)N)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N=[N+]=[N-])C=3)=CC=2)=C1 YQVMOFXECVKZFY-UHFFFAOYSA-N 0.000 description 2
- WABLMCKXQVPQGB-UHFFFAOYSA-N 3-[[4-(6-azidopyrimidin-4-yl)oxyphenyl]carbamoylamino]-n-methyl-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)NC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N=[N+]=[N-])C=3)=CC=2)=C1 WABLMCKXQVPQGB-UHFFFAOYSA-N 0.000 description 2
- ARNCEEFAHWTPDR-UHFFFAOYSA-N 3-[[4-(6-chloropyrimidin-4-yl)oxyphenyl]carbamoylamino]-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)N)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=C1 ARNCEEFAHWTPDR-UHFFFAOYSA-N 0.000 description 2
- NFFBQZMQKOSWLZ-UHFFFAOYSA-N 3-[[4-(6-chloropyrimidin-4-yl)oxyphenyl]carbamoylamino]-n-methyl-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)NC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=C1 NFFBQZMQKOSWLZ-UHFFFAOYSA-N 0.000 description 2
- WOSFZFTWHRLVMV-UHFFFAOYSA-N 3-amino-5-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 WOSFZFTWHRLVMV-UHFFFAOYSA-N 0.000 description 2
- FRNOEYRXTZZHLD-UHFFFAOYSA-N 3-amino-n-methyl-5-(trifluoromethyl)benzamide Chemical compound CNC(=O)C1=CC(N)=CC(C(F)(F)F)=C1 FRNOEYRXTZZHLD-UHFFFAOYSA-N 0.000 description 2
- HJTLKVYOWNTDPF-UHFFFAOYSA-N 3-bromo-5-(trifluoromethyl)aniline Chemical compound NC1=CC(Br)=CC(C(F)(F)F)=C1 HJTLKVYOWNTDPF-UHFFFAOYSA-N 0.000 description 2
- IWFHKUAMDAWLNA-UHFFFAOYSA-N 3-chloro-4-[(4-ethylpiperazin-1-yl)methyl]aniline Chemical compound C1CN(CC)CCN1CC1=CC=C(N)C=C1Cl IWFHKUAMDAWLNA-UHFFFAOYSA-N 0.000 description 2
- PNCXCCIFVAKWOB-UHFFFAOYSA-N 4-(2-chloropyrimidin-4-yl)oxy-2-(trifluoromethyl)aniline Chemical compound C1=C(C(F)(F)F)C(N)=CC=C1OC1=CC=NC(Cl)=N1 PNCXCCIFVAKWOB-UHFFFAOYSA-N 0.000 description 2
- QKWDWXUNPDIWJD-UHFFFAOYSA-N 4-(2-chloropyrimidin-4-yl)oxy-2-methylaniline Chemical compound C1=C(N)C(C)=CC(OC=2N=C(Cl)N=CC=2)=C1 QKWDWXUNPDIWJD-UHFFFAOYSA-N 0.000 description 2
- UTMUJKGPQJORKZ-UHFFFAOYSA-N 4-(3-bromophenyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1C1=CC=CC(Br)=C1 UTMUJKGPQJORKZ-UHFFFAOYSA-N 0.000 description 2
- CANAKSZMEGWIQM-UHFFFAOYSA-N 4-(4-aminophenoxy)-n-methylpyrimidin-2-amine Chemical compound CNC1=NC=CC(OC=2C=CC(N)=CC=2)=N1 CANAKSZMEGWIQM-UHFFFAOYSA-N 0.000 description 2
- KDEOQVWQDMGPHG-UHFFFAOYSA-N 4-(4-bromophenyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1C1=CC=C(Br)C=C1 KDEOQVWQDMGPHG-UHFFFAOYSA-N 0.000 description 2
- JMQDHSMCRQZUOY-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1C1=CC=C(Cl)C=C1 JMQDHSMCRQZUOY-UHFFFAOYSA-N 0.000 description 2
- IWJNMSWNXYOZAQ-UHFFFAOYSA-N 4-(4-nitrophenoxy)pyrimidin-2-amine Chemical compound NC1=NC=CC(OC=2C=CC(=CC=2)[N+]([O-])=O)=N1 IWJNMSWNXYOZAQ-UHFFFAOYSA-N 0.000 description 2
- CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 2
- GNYMTNISHULOOR-UHFFFAOYSA-N 4-[(4-ethylpiperazin-1-yl)methyl]-3-methylaniline Chemical compound C1CN(CC)CCN1CC1=CC=C(N)C=C1C GNYMTNISHULOOR-UHFFFAOYSA-N 0.000 description 2
- QJLBLWPWJMKYJA-UHFFFAOYSA-N 4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)aniline Chemical compound C1CN(C(C)C)CCN1CC1=CC=C(N)C=C1C(F)(F)F QJLBLWPWJMKYJA-UHFFFAOYSA-N 0.000 description 2
- SRUFLPZZCUEOTK-UHFFFAOYSA-N 4-[2-(4-ethylpiperazin-1-yl)ethyl]-3-(trifluoromethyl)aniline Chemical compound C1CN(CC)CCN1CCC1=CC=C(N)C=C1C(F)(F)F SRUFLPZZCUEOTK-UHFFFAOYSA-N 0.000 description 2
- BNEFRCZMWGNXQY-UHFFFAOYSA-N 4-[[6-(4-nitrophenoxy)pyrimidin-4-yl]amino]phenol Chemical compound C1=CC(O)=CC=C1NC1=CC(OC=2C=CC(=CC=2)[N+]([O-])=O)=NC=N1 BNEFRCZMWGNXQY-UHFFFAOYSA-N 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- TZXIWIUCQFFQDT-UHFFFAOYSA-N 4-chloro-6-(4-nitrophenoxy)pyrimidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC(Cl)=NC=N1 TZXIWIUCQFFQDT-UHFFFAOYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-CFWMRBGOSA-N 5j49q6b70f 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=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 OGWKCGZFUXNPDA-CFWMRBGOSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- OONFNUWBHFSNBT-HXUWFJFHSA-N AEE788 Chemical compound C1CN(CC)CCN1CC1=CC=C(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)C=C1 OONFNUWBHFSNBT-HXUWFJFHSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229940122815 Aromatase inhibitor Drugs 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 229940122361 Bisphosphonate Drugs 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 241000208199 Buxus sempervirens Species 0.000 description 2
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 2
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- AADVCYNFEREWOS-OBRABYBLSA-N Discodermolide Chemical compound C=C\C=C/[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C\C(C)=C/[C@H](C)[C@@H](O)[C@@H](C)\C=C/[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C AADVCYNFEREWOS-OBRABYBLSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102000050554 Eph Family Receptors Human genes 0.000 description 2
- 108091008815 Eph receptors Proteins 0.000 description 2
- 108010055323 EphB4 Receptor Proteins 0.000 description 2
- 102000030797 EphB4 Receptor Human genes 0.000 description 2
- 102400001368 Epidermal growth factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- 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 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102400000932 Gonadoliberin-1 Human genes 0.000 description 2
- 101500026183 Homo sapiens Gonadoliberin-1 Proteins 0.000 description 2
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 229940124761 MMP inhibitor Drugs 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 206010073149 Multiple endocrine neoplasia Type 2 Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 102100028680 Protein patched homolog 1 Human genes 0.000 description 2
- 101710161390 Protein patched homolog 1 Proteins 0.000 description 2
- 102100036894 Protein patched homolog 2 Human genes 0.000 description 2
- 101710161395 Protein patched homolog 2 Proteins 0.000 description 2
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 2
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 2
- 229960002184 abarelix Drugs 0.000 description 2
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 2
- 108010023617 abarelix Proteins 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229960004343 alendronic acid Drugs 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 229960002932 anastrozole Drugs 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000002280 anti-androgenic effect Effects 0.000 description 2
- 229940046836 anti-estrogen Drugs 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000000051 antiandrogen Substances 0.000 description 2
- 239000002814 antineoplastic antimetabolite Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 229940087620 aromasin Drugs 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229930195545 bengamide Natural products 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- DCGJMNHXBNOLRX-UHFFFAOYSA-N benzoyl 4-[[4-[[4-(6-chloropyrimidin-4-yl)oxyphenyl]carbamoylamino]-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound C=1C=C(CN2CCN(CC2)C(=O)OC(=O)C=2C=CC=CC=2)C(C(F)(F)F)=CC=1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 DCGJMNHXBNOLRX-UHFFFAOYSA-N 0.000 description 2
- BJJPOTSGJIFYLW-UHFFFAOYSA-N benzoyl 4-[[4-amino-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound FC(F)(F)C1=CC(N)=CC=C1CN1CCN(C(=O)OC(=O)C=2C=CC=CC=2)CC1 BJJPOTSGJIFYLW-UHFFFAOYSA-N 0.000 description 2
- DDBSFTRRSABZGM-UHFFFAOYSA-N benzyl 4-[[4-amino-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound FC(F)(F)C1=CC(N)=CC=C1CN1CCN(C(=O)OCC=2C=CC=CC=2)CC1 DDBSFTRRSABZGM-UHFFFAOYSA-N 0.000 description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 150000004663 bisphosphonates Chemical class 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229940047495 celebrex Drugs 0.000 description 2
- 229960000590 celecoxib Drugs 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 2
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 2
- 229960002286 clodronic acid Drugs 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 125000004980 cyclopropylene group Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- 229930013356 epothilone Natural products 0.000 description 2
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 239000000328 estrogen antagonist Substances 0.000 description 2
- 229960005167 everolimus Drugs 0.000 description 2
- 229960000255 exemestane Drugs 0.000 description 2
- 229950011548 fadrozole Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 229960004421 formestane Drugs 0.000 description 2
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 229960002258 fulvestrant Drugs 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 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
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229940080856 gleevec Drugs 0.000 description 2
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
- 229960001442 gonadorelin Drugs 0.000 description 2
- 229960002913 goserelin Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 229960005236 ibandronic acid Drugs 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- 229960003881 letrozole Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 2
- 229940124302 mTOR inhibitor Drugs 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 2
- 229950010895 midostaurin Drugs 0.000 description 2
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 2
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 2
- VUMWEMYNYUFCLV-UHFFFAOYSA-N n-(3-methoxyphenyl)-6-(4-nitrophenoxy)pyrimidin-4-amine Chemical compound COC1=CC=CC(NC=2N=CN=C(OC=3C=CC(=CC=3)[N+]([O-])=O)C=2)=C1 VUMWEMYNYUFCLV-UHFFFAOYSA-N 0.000 description 2
- DEOZOLHFCIOLML-UHFFFAOYSA-N n-[4-(2-amino-3,3-dimethylbutan-2-yl)-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound CC(C)(C)C(C)(N)C1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F DEOZOLHFCIOLML-UHFFFAOYSA-N 0.000 description 2
- JFOUPEXZGYIBRR-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-6-(4-nitrophenoxy)pyrimidin-4-amine Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1NC1=CC(OC=2C=CC(=CC=2)[N+]([O-])=O)=NC=N1 JFOUPEXZGYIBRR-UHFFFAOYSA-N 0.000 description 2
- RHHKKLXBQOIVQS-UHFFFAOYSA-N n-methyl-3-[[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]carbamoylamino]-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)NC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(NC)C=3)=CC=2)=C1 RHHKKLXBQOIVQS-UHFFFAOYSA-N 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- NLRKCXQQSUWLCH-UHFFFAOYSA-N nitrosobenzene Chemical compound O=NC1=CC=CC=C1 NLRKCXQQSUWLCH-UHFFFAOYSA-N 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 229960003978 pamidronic acid Drugs 0.000 description 2
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 108010077182 raf Kinases Proteins 0.000 description 2
- 102000009929 raf Kinases Human genes 0.000 description 2
- 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 2
- BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 2
- 229960002119 raloxifene hydrochloride Drugs 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 229960000759 risedronic acid Drugs 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 238000003419 tautomerization reaction Methods 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 2
- 229960005324 tiludronic acid Drugs 0.000 description 2
- 229960000303 topotecan Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- KDQAABAKXDWYSZ-PNYVAJAMSA-N vinblastine sulfate Chemical compound OS(O)(=O)=O.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 KDQAABAKXDWYSZ-PNYVAJAMSA-N 0.000 description 2
- 229960004982 vinblastine sulfate Drugs 0.000 description 2
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.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=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 2
- 229960002110 vincristine sulfate Drugs 0.000 description 2
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 2
- 229960000237 vorinostat Drugs 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 229960004276 zoledronic acid Drugs 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- KJZLJGZZDNGGCA-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methanol Chemical compound CN1CCC(CO)CC1 KJZLJGZZDNGGCA-UHFFFAOYSA-N 0.000 description 1
- RKPDUJSRMRUTGX-UHFFFAOYSA-N (2-chloro-4-nitrophenyl)-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1Cl RKPDUJSRMRUTGX-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- AFSSVCNPDKKSRR-UHFFFAOYSA-N (3-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Br)=C1 AFSSVCNPDKKSRR-UHFFFAOYSA-N 0.000 description 1
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
- SMHUVDSCYMEJOA-UHFFFAOYSA-N (4-amino-2-chlorophenyl)-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(N)C=C1Cl SMHUVDSCYMEJOA-UHFFFAOYSA-N 0.000 description 1
- CZOVQNOOMYMVEP-UHFFFAOYSA-N (4-amino-2-methylphenyl)-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(N)C=C1C CZOVQNOOMYMVEP-UHFFFAOYSA-N 0.000 description 1
- NSBYIXFHERKEPP-UHFFFAOYSA-N (4-aminophenyl)-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(N)C=C1 NSBYIXFHERKEPP-UHFFFAOYSA-N 0.000 description 1
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- PNDCXBGTNCFIGP-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[3-nitro-5-(trifluoromethyl)phenyl]methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 PNDCXBGTNCFIGP-UHFFFAOYSA-N 0.000 description 1
- UDIALNGJZCKOIC-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-nitro-2-(trifluoromethyl)phenyl]methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1C(F)(F)F UDIALNGJZCKOIC-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- QDVBKXJMLILLLB-UHFFFAOYSA-N 1,4'-bipiperidine Chemical group C1CCCCN1C1CCNCC1 QDVBKXJMLILLLB-UHFFFAOYSA-N 0.000 description 1
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 1
- VPBYZLCHOKSGRX-UHFFFAOYSA-N 1-[2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-propylurea Chemical compound C1=C(Cl)C(NC(=O)NCCC)=CC=C1OC1=NC=NC2=CC(OC)=C(OC)C=C12 VPBYZLCHOKSGRX-UHFFFAOYSA-N 0.000 description 1
- FDBJWMMMDZFDBN-UHFFFAOYSA-N 1-[3-(aminomethyl)-5-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C=C(CN)C=3)C(F)(F)F)=CC=2)=N1 FDBJWMMMDZFDBN-UHFFFAOYSA-N 0.000 description 1
- DTIZGNLUMDXFDB-UHFFFAOYSA-N 1-[3-(azetidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C=1C(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=CC(C(F)(F)F)=CC=1CN1CCC1 DTIZGNLUMDXFDB-UHFFFAOYSA-N 0.000 description 1
- VVITYWNNLYLVTD-UHFFFAOYSA-N 1-[3-(azetidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C=C(CN4CCC4)C=3)C(F)(F)F)=CC=2)=N1 VVITYWNNLYLVTD-UHFFFAOYSA-N 0.000 description 1
- NMHAJZDFPLYTAU-UHFFFAOYSA-N 1-[3-(diethylaminomethyl)-5-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound FC(F)(F)C1=CC(CN(CC)CC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(NC)C=3)=CC=2)=C1 NMHAJZDFPLYTAU-UHFFFAOYSA-N 0.000 description 1
- PBRVYHVNDHIEBK-UHFFFAOYSA-N 1-[3-(methylaminomethyl)-5-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound FC(F)(F)C1=CC(CNC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(NC)C=3)=CC=2)=C1 PBRVYHVNDHIEBK-UHFFFAOYSA-N 0.000 description 1
- NHPVZNSROCJABL-UHFFFAOYSA-N 1-[3-chloro-4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C1CN(CC)CCN1CC(C(=C1)Cl)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 NHPVZNSROCJABL-UHFFFAOYSA-N 0.000 description 1
- AGSGXEGYJMCIAA-UHFFFAOYSA-N 1-[4-(2-amino-3,3-dimethylbutan-2-yl)-3-(trifluoromethyl)phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C1=C(C(F)(F)F)C(C(C)(N)C(C)(C)C)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 AGSGXEGYJMCIAA-UHFFFAOYSA-N 0.000 description 1
- YHQBBTKNOXVPRO-UHFFFAOYSA-N 1-[4-(2-aminopyrimidin-4-yl)oxyphenyl]-3-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]urea Chemical compound NC1=NC=CC(OC=2C=CC(NC(=O)NC=3C=C(C(CN4CCNCC4)=CC=3)C(F)(F)F)=CC=2)=N1 YHQBBTKNOXVPRO-UHFFFAOYSA-N 0.000 description 1
- FNKYYAICISKQJO-UHFFFAOYSA-N 1-[4-(2-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC(N)=N1 FNKYYAICISKQJO-UHFFFAOYSA-N 0.000 description 1
- NWSQNFGOSYKUIX-UHFFFAOYSA-N 1-[4-(2-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-tert-butylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC(N)=N1 NWSQNFGOSYKUIX-UHFFFAOYSA-N 0.000 description 1
- MXXCXWLTVFWVRX-UHFFFAOYSA-N 1-[4-(2-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(dimethylamino)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(C(F)(F)F)C(CN(C)C)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC(Cl)=N1 MXXCXWLTVFWVRX-UHFFFAOYSA-N 0.000 description 1
- BNJKPRCXWRCTBG-UHFFFAOYSA-N 1-[4-(3-bromophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-(trifluoromethyl)phenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C(NC(=O)NC=3C=C(C(C=4C=C(Br)C=CC=4)=CC=3)C(F)(F)F)=CC=2)C(F)(F)F)=N1 BNJKPRCXWRCTBG-UHFFFAOYSA-N 0.000 description 1
- AVLFQJJGYWYJHW-UHFFFAOYSA-N 1-[4-(3-bromophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-methylphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C)C(NC(=O)NC=3C=C(C(C=4C=C(Br)C=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 AVLFQJJGYWYJHW-UHFFFAOYSA-N 0.000 description 1
- WGISYJLOFAEHNW-UHFFFAOYSA-N 1-[4-(3-chlorophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-(trifluoromethyl)phenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C(NC(=O)NC=3C=C(C(C=4C=C(Cl)C=CC=4)=CC=3)C(F)(F)F)=CC=2)C(F)(F)F)=N1 WGISYJLOFAEHNW-UHFFFAOYSA-N 0.000 description 1
- NTJWKXQMERKMNR-UHFFFAOYSA-N 1-[4-(3-chlorophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxyphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=C(Cl)C=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 NTJWKXQMERKMNR-UHFFFAOYSA-N 0.000 description 1
- ZQTDWSOFENMTRJ-UHFFFAOYSA-N 1-[4-(4-bromophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-(trifluoromethyl)phenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C(NC(=O)NC=3C=C(C(C=4C=CC(Br)=CC=4)=CC=3)C(F)(F)F)=CC=2)C(F)(F)F)=N1 ZQTDWSOFENMTRJ-UHFFFAOYSA-N 0.000 description 1
- MQPPEGIPSKRXJF-UHFFFAOYSA-N 1-[4-(4-bromophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-methylphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C)C(NC(=O)NC=3C=C(C(C=4C=CC(Br)=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 MQPPEGIPSKRXJF-UHFFFAOYSA-N 0.000 description 1
- HDKCPDGOOPIHHP-UHFFFAOYSA-N 1-[4-(4-bromophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxyphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=CC(Br)=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 HDKCPDGOOPIHHP-UHFFFAOYSA-N 0.000 description 1
- MRIOCAORXNNEHV-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-(trifluoromethyl)phenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C(NC(=O)NC=3C=C(C(C=4C=CC(Cl)=CC=4)=CC=3)C(F)(F)F)=CC=2)C(F)(F)F)=N1 MRIOCAORXNNEHV-UHFFFAOYSA-N 0.000 description 1
- FSDRVCAOMVKEPQ-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-3-(trifluoromethyl)phenyl]-3-[4-[2-[4-(dimethylamino)butylamino]pyrimidin-4-yl]oxy-2-methylphenyl]urea Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C)C(NC(=O)NC=3C=C(C(C=4C=CC(Cl)=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 FSDRVCAOMVKEPQ-UHFFFAOYSA-N 0.000 description 1
- CEVNCDIJPVCSMF-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[3-(6-methylpyridin-2-yl)-5-(trifluoromethyl)phenyl]urea Chemical compound CC1=CC=CC(C=2C=C(C=C(NC(=O)NC=3C=CC(OC=4N=CN=C(N)C=4)=CC=3)C=2)C(F)(F)F)=N1 CEVNCDIJPVCSMF-UHFFFAOYSA-N 0.000 description 1
- LOSXKQWNLQOFML-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[3-(azetidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C=C(CN4CCC4)C=3)C(F)(F)F)=CC=2)=N1 LOSXKQWNLQOFML-UHFFFAOYSA-N 0.000 description 1
- FONMDHKHNSFUAY-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[3-(diethylaminomethyl)-5-(trifluoromethyl)phenyl]urea Chemical compound FC(F)(F)C1=CC(CN(CC)CC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N)C=3)=CC=2)=C1 FONMDHKHNSFUAY-UHFFFAOYSA-N 0.000 description 1
- LJGYQVUVFLJFGZ-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(CC)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(N)=NC=N1 LJGYQVUVFLJFGZ-UHFFFAOYSA-N 0.000 description 1
- ZTFNIEKXKYJBCD-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(N)=NC=N1 ZTFNIEKXKYJBCD-UHFFFAOYSA-N 0.000 description 1
- YIMULKGGTBWQSB-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[4-pyridin-2-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4N=CC=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 YIMULKGGTBWQSB-UHFFFAOYSA-N 0.000 description 1
- AZUXKEWEYGUQKV-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[4-pyridin-3-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=NC=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 AZUXKEWEYGUQKV-UHFFFAOYSA-N 0.000 description 1
- FYORDDDXJCUTES-UHFFFAOYSA-N 1-[4-(6-aminopyrimidin-4-yl)oxyphenyl]-3-[4-pyridin-4-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=CN=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 FYORDDDXJCUTES-UHFFFAOYSA-N 0.000 description 1
- DPCNKRSOJLOOAW-UHFFFAOYSA-N 1-[4-(6-azidopyrimidin-4-yl)oxyphenyl]-3-[3-[(4-propan-2-ylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC1=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N=[N+]=[N-])C=3)=CC=2)=CC(C(F)(F)F)=C1 DPCNKRSOJLOOAW-UHFFFAOYSA-N 0.000 description 1
- QWBILXJMCBUJQM-UHFFFAOYSA-N 1-[4-(6-azidopyrimidin-4-yl)oxyphenyl]-3-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(N=[N+]=[N-])=NC=N1 QWBILXJMCBUJQM-UHFFFAOYSA-N 0.000 description 1
- HERDTTKBYAUZHU-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[3-(diethylaminomethyl)-5-(trifluoromethyl)phenyl]urea Chemical compound FC(F)(F)C1=CC(CN(CC)CC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=C1 HERDTTKBYAUZHU-UHFFFAOYSA-N 0.000 description 1
- QJFKRPAOQFKIHP-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound FC(F)(F)C1=CC=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=C1 QJFKRPAOQFKIHP-UHFFFAOYSA-N 0.000 description 1
- JYMYPBXWQZHVIB-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCN1CC1=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=CC(C(F)(F)F)=C1 JYMYPBXWQZHVIB-UHFFFAOYSA-N 0.000 description 1
- QGEWDTXGXJMMOY-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[3-[(4-propan-2-ylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC1=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)=CC(C(F)(F)F)=C1 QGEWDTXGXJMMOY-UHFFFAOYSA-N 0.000 description 1
- DYNZPBLCFPROHH-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-(1-methylpiperidin-4-yl)oxy-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCC1OC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 DYNZPBLCFPROHH-UHFFFAOYSA-N 0.000 description 1
- MMTLDMRLPIMYOU-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-(4-piperidin-1-ylpiperidin-1-yl)-3-(trifluoromethyl)phenyl]urea Chemical compound C=1C=C(N2CCC(CC2)N2CCCCC2)C(C(F)(F)F)=CC=1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 MMTLDMRLPIMYOU-UHFFFAOYSA-N 0.000 description 1
- IQNREWFUDSBZHD-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-(diethylaminomethyl)-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(C(F)(F)F)C(CN(CC)CC)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 IQNREWFUDSBZHD-UHFFFAOYSA-N 0.000 description 1
- UNQKIIHYQNBXMC-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(1-methylpiperidin-4-yl)methoxy]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCC1COC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 UNQKIIHYQNBXMC-UHFFFAOYSA-N 0.000 description 1
- MVMKZHVOQYNBEM-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(4,5-dimethylimidazol-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound CC1=C(C)N=CN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 MVMKZHVOQYNBEM-UHFFFAOYSA-N 0.000 description 1
- MFWFCAYOAPOGLJ-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(4-ethylpiperazin-1-yl)methyl]-3-methylphenyl]urea Chemical compound C1CN(CC)CCN1CC(C(=C1)C)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 MFWFCAYOAPOGLJ-UHFFFAOYSA-N 0.000 description 1
- GJXPJQXHRIWGEX-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]urea Chemical compound C1CN(CC)CCN1CC(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 GJXPJQXHRIWGEX-UHFFFAOYSA-N 0.000 description 1
- VQZZJYMSCVRAGS-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 VQZZJYMSCVRAGS-UHFFFAOYSA-N 0.000 description 1
- RRHJVQWXWHGMHW-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 RRHJVQWXWHGMHW-UHFFFAOYSA-N 0.000 description 1
- HYYHYQJBRFGFOS-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[(dimethylamino)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(C(F)(F)F)C(CN(C)C)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 HYYHYQJBRFGFOS-UHFFFAOYSA-N 0.000 description 1
- IOMYWNBBHYRORI-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[2-(4-ethylpiperazin-1-yl)ethyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(CC)CCN1CCC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 IOMYWNBBHYRORI-UHFFFAOYSA-N 0.000 description 1
- AMIOONZHRWIJDK-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[4-(2,2-dimethylpropyl)piperazin-1-yl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(CC(C)(C)C)CCN1C(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 AMIOONZHRWIJDK-UHFFFAOYSA-N 0.000 description 1
- UMAWGHRBAYVDRQ-UHFFFAOYSA-N 1-[4-(6-chloropyrimidin-4-yl)oxyphenyl]-3-[4-[[4-[(4-methoxyphenyl)methyl]piperazin-1-yl]methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(OC)=CC=C1CN1CCN(CC=2C(=CC(NC(=O)NC=3C=CC(OC=4N=CN=C(Cl)C=4)=CC=3)=CC=2)C(F)(F)F)CC1 UMAWGHRBAYVDRQ-UHFFFAOYSA-N 0.000 description 1
- NEOVQPWLEKAGLQ-UHFFFAOYSA-N 1-[4-(azetidin-1-ylmethyl)-3-(trifluoromethyl)phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C=1C=C(CN2CCC2)C(C(F)(F)F)=CC=1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 NEOVQPWLEKAGLQ-UHFFFAOYSA-N 0.000 description 1
- NDUSOXOREGNPNO-UHFFFAOYSA-N 1-[4-[(4-tert-butylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C1CN(C(C)(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC(Cl)=NC=N1 NDUSOXOREGNPNO-UHFFFAOYSA-N 0.000 description 1
- OEDSBLPSKCIRHU-UHFFFAOYSA-N 1-[4-[(4-tert-butylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[2-(methylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound CNC1=NC=CC(OC=2C=CC(NC(=O)NC=3C=C(C(CN4CCN(CC4)C(C)(C)C)=CC=3)C(F)(F)F)=CC=2)=N1 OEDSBLPSKCIRHU-UHFFFAOYSA-N 0.000 description 1
- ZSSQBWAHXBJOMG-UHFFFAOYSA-N 1-[4-[1-amino-2-(4-cyanophenyl)ethyl]-3-(trifluoromethyl)phenyl]-3-[4-(6-chloropyrimidin-4-yl)oxyphenyl]urea Chemical compound C=1C=C(NC(=O)NC=2C=CC(OC=3N=CN=C(Cl)C=3)=CC=2)C=C(C(F)(F)F)C=1C(N)CC1=CC=C(C#N)C=C1 ZSSQBWAHXBJOMG-UHFFFAOYSA-N 0.000 description 1
- VWQZRBXWHQYGPP-UHFFFAOYSA-N 1-[4-[2-(3-methoxyanilino)pyrimidin-4-yl]oxyphenyl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound COC1=CC=CC(NC=2N=C(OC=3C=CC(NC(=O)NC=4C=C(C(CN5CCN(C)CC5)=CC=4)C(F)(F)F)=CC=3)C=CN=2)=C1 VWQZRBXWHQYGPP-UHFFFAOYSA-N 0.000 description 1
- TZKBNGYRAFKRJC-UHFFFAOYSA-N 1-[4-[2-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea Chemical compound CNC1=NC=CC(OC=2C=CC(NC(=O)NC=3C=C(C(CN4CCN(CC4)C(C)C)=CC=3)C(F)(F)F)=CC=2)=N1 TZKBNGYRAFKRJC-UHFFFAOYSA-N 0.000 description 1
- NHVCLGYTSZLYSV-UHFFFAOYSA-N 1-[4-[6-(5-chloro-2-methoxyanilino)pyrimidin-4-yl]oxyphenyl]-3-[4-morpholin-4-yl-3-(trifluoromethyl)phenyl]urea Chemical compound COC1=CC=C(Cl)C=C1NC1=CC(OC=2C=CC(NC(=O)NC=3C=C(C(N4CCOCC4)=CC=3)C(F)(F)F)=CC=2)=NC=N1 NHVCLGYTSZLYSV-UHFFFAOYSA-N 0.000 description 1
- UGOYTHLEFQMHQH-UHFFFAOYSA-N 1-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[3-[(4-propan-2-ylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C=C(CN4CCN(CC4)C(C)C)C=3)C(F)(F)F)=CC=2)=N1 UGOYTHLEFQMHQH-UHFFFAOYSA-N 0.000 description 1
- UVNVIROUGNTKQW-UHFFFAOYSA-N 1-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(CN4CCN(CC4)C(C)C)=CC=3)C(F)(F)F)=CC=2)=N1 UVNVIROUGNTKQW-UHFFFAOYSA-N 0.000 description 1
- FEHQLEJVWUIHCB-UHFFFAOYSA-N 1-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[4-pyridin-2-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4N=CC=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 FEHQLEJVWUIHCB-UHFFFAOYSA-N 0.000 description 1
- UMLASAPNDPEHIS-UHFFFAOYSA-N 1-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[4-pyridin-3-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=NC=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 UMLASAPNDPEHIS-UHFFFAOYSA-N 0.000 description 1
- JFKCUSMZNIGVPL-UHFFFAOYSA-N 1-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[4-pyridin-4-yl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(C=4C=CN=CC=4)=CC=3)C(F)(F)F)=CC=2)=N1 JFKCUSMZNIGVPL-UHFFFAOYSA-N 0.000 description 1
- DNTHMWUMRGOJRY-UHFFFAOYSA-N 1-fluoro-4-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(C(F)(F)F)=C1 DNTHMWUMRGOJRY-UHFFFAOYSA-N 0.000 description 1
- SXJYSIBLFGQAND-UHFFFAOYSA-N 1-isocyanato-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(N=C=O)=C1 SXJYSIBLFGQAND-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- DVFVNJHIVAPTMS-UHFFFAOYSA-N 1-methyl-2-(trifluoromethyl)benzene Chemical compound CC1=CC=CC=C1C(F)(F)F DVFVNJHIVAPTMS-UHFFFAOYSA-N 0.000 description 1
- VSOQSAUTGLUFDR-UHFFFAOYSA-N 1-methyl-4-[[4-nitro-2-(trifluoromethyl)phenoxy]methyl]piperidine Chemical compound C1CN(C)CCC1COC1=CC=C([N+]([O-])=O)C=C1C(F)(F)F VSOQSAUTGLUFDR-UHFFFAOYSA-N 0.000 description 1
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- PVMNSAIKFPWDQG-UHFFFAOYSA-N 1-tert-butylpiperazine Chemical compound CC(C)(C)N1CCNCC1 PVMNSAIKFPWDQG-UHFFFAOYSA-N 0.000 description 1
- 101710175516 14 kDa zinc-binding protein Proteins 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- RGLSEWDOTRUPBQ-UHFFFAOYSA-N 2,2,2-trifluoro-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]acetamide Chemical compound C1CN(C)CCN1CC1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F RGLSEWDOTRUPBQ-UHFFFAOYSA-N 0.000 description 1
- GSLSXPROLXSOMF-UHFFFAOYSA-N 2,2,2-trifluoro-n-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]acetamide Chemical compound C1CN(C(C)C)CCN1CC1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F GSLSXPROLXSOMF-UHFFFAOYSA-N 0.000 description 1
- RFSRZWVCAVHHHS-UHFFFAOYSA-N 2,2,2-trifluoro-n-[4-methyl-3-(trifluoromethyl)phenyl]acetamide Chemical compound CC1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F RFSRZWVCAVHHHS-UHFFFAOYSA-N 0.000 description 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 1
- VLNVCMOMPHXWLG-UHFFFAOYSA-N 2-(4-nitrophenoxy)pyrimidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=NC=CC=N1 VLNVCMOMPHXWLG-UHFFFAOYSA-N 0.000 description 1
- FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 description 1
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 1
- GJXYXVAWOPUQOV-UHFFFAOYSA-N 2-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]acetamide Chemical compound CN1CCN(CC1)CC1=C(C=C(C=C1)CC(=O)N)C(F)(F)F GJXYXVAWOPUQOV-UHFFFAOYSA-N 0.000 description 1
- YZTDLMPJWMSPBE-UHFFFAOYSA-N 2-[4-amino-2-(trifluoromethyl)phenyl]-1-(4-ethylpiperazin-1-yl)ethanone Chemical compound C1CN(CC)CCN1C(=O)CC1=CC=C(N)C=C1C(F)(F)F YZTDLMPJWMSPBE-UHFFFAOYSA-N 0.000 description 1
- WWYLSNCPPXAEER-UHFFFAOYSA-N 2-[4-nitro-2-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1C(F)(F)F WWYLSNCPPXAEER-UHFFFAOYSA-N 0.000 description 1
- WZIMSXIXZTUBSO-UHFFFAOYSA-N 2-[[bis(carboxymethyl)amino]methyl-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CN(CC(O)=O)CC(O)=O WZIMSXIXZTUBSO-UHFFFAOYSA-N 0.000 description 1
- SOHDPICLICFSOP-UHFFFAOYSA-N 2-bromo-6-methylpyridine Chemical compound CC1=CC=CC(Br)=N1 SOHDPICLICFSOP-UHFFFAOYSA-N 0.000 description 1
- HBFZTSPCVMJHNW-UHFFFAOYSA-N 2-chloro-4-(4-isocyanatophenoxy)pyrimidine Chemical compound ClC1=NC=CC(OC=2C=CC(=CC=2)N=C=O)=N1 HBFZTSPCVMJHNW-UHFFFAOYSA-N 0.000 description 1
- RNTFKDBRMXYEPR-UHFFFAOYSA-N 2-methyl-4-nitrobenzonitrile Chemical compound CC1=CC([N+]([O-])=O)=CC=C1C#N RNTFKDBRMXYEPR-UHFFFAOYSA-N 0.000 description 1
- VRESBNUEIKZECD-UHFFFAOYSA-N 2-methyltetrazole Chemical compound CN1N=CN=N1 VRESBNUEIKZECD-UHFFFAOYSA-N 0.000 description 1
- POSKCQXWHNDYKW-UHFFFAOYSA-N 2-nitro-5-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=CC=C1[N+]([O-])=O POSKCQXWHNDYKW-UHFFFAOYSA-N 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QMQZJKBZHXMSNK-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)aniline Chemical compound C1CN(C)CCN1C1=CC(N)=CC(C(F)(F)F)=C1 QMQZJKBZHXMSNK-UHFFFAOYSA-N 0.000 description 1
- HUGCHPDEYNXVPV-UHFFFAOYSA-N 3-(diethylaminomethyl)-5-(trifluoromethyl)aniline Chemical compound CCN(CC)CC1=CC(N)=CC(C(F)(F)F)=C1 HUGCHPDEYNXVPV-UHFFFAOYSA-N 0.000 description 1
- HXHAJRMTJXHJJZ-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 HXHAJRMTJXHJJZ-UHFFFAOYSA-N 0.000 description 1
- RYCQDSXIMURQDP-UHFFFAOYSA-N 3-[[4-(6-aminopyrimidin-4-yl)oxyphenyl]carbamoylamino]-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)N)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N)C=3)=CC=2)=C1 RYCQDSXIMURQDP-UHFFFAOYSA-N 0.000 description 1
- MCHKOFLGTNCGPA-UHFFFAOYSA-N 3-[[4-(6-aminopyrimidin-4-yl)oxyphenyl]carbamoylamino]-n-methyl-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)NC)=CC(NC(=O)NC=2C=CC(OC=3N=CN=C(N)C=3)=CC=2)=C1 MCHKOFLGTNCGPA-UHFFFAOYSA-N 0.000 description 1
- DQKUWRMBWLODDY-UHFFFAOYSA-N 3-[[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]carbamoylamino]-5-(trifluoromethyl)benzamide Chemical compound C1=NC(NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C=C(C=3)C(N)=O)C(F)(F)F)=CC=2)=N1 DQKUWRMBWLODDY-UHFFFAOYSA-N 0.000 description 1
- GEFMAOZBMLYEJL-UHFFFAOYSA-N 3-[[4-[6-[4-[tert-butyl(dimethyl)silyl]oxyanilino]pyrimidin-4-yl]oxyphenyl]carbamoylamino]-5-(trifluoromethyl)benzamide Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1NC1=CC(OC=2C=CC(NC(=O)NC=3C=C(C=C(C=3)C(N)=O)C(F)(F)F)=CC=2)=NC=N1 GEFMAOZBMLYEJL-UHFFFAOYSA-N 0.000 description 1
- RQSXRGSPGHZKFT-UHFFFAOYSA-M 3-amino-5-bromobenzoate Chemical compound NC1=CC(Br)=CC(C([O-])=O)=C1 RQSXRGSPGHZKFT-UHFFFAOYSA-M 0.000 description 1
- RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 description 1
- IVMMVWKAROMENU-UHFFFAOYSA-N 3-nitro-5-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 IVMMVWKAROMENU-UHFFFAOYSA-N 0.000 description 1
- YBFMXXRONADDSH-UHFFFAOYSA-N 3-pyridin-2-yl-5-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC(C=2N=CC=CC=2)=C1 YBFMXXRONADDSH-UHFFFAOYSA-N 0.000 description 1
- YSWBFLWKAIRHEI-UHFFFAOYSA-N 4,5-dimethyl-1h-imidazole Chemical compound CC=1N=CNC=1C YSWBFLWKAIRHEI-UHFFFAOYSA-N 0.000 description 1
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 1
- FYCJYWMLKZJUNJ-UHFFFAOYSA-N 4-(1-methylpiperidin-4-yl)oxy-3-(trifluoromethyl)aniline Chemical compound C1CN(C)CCC1OC1=CC=C(N)C=C1C(F)(F)F FYCJYWMLKZJUNJ-UHFFFAOYSA-N 0.000 description 1
- WAYAAHLRSCYPCS-UHFFFAOYSA-N 4-(2-amino-3,3-dimethylbutan-2-yl)-3-(trifluoromethyl)aniline Chemical compound CC(C)(C)C(C)(N)C1=CC=C(N)C=C1C(F)(F)F WAYAAHLRSCYPCS-UHFFFAOYSA-N 0.000 description 1
- BOXBZVMLJCORGG-UHFFFAOYSA-N 4-(3-chlorophenyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1C1=CC=CC(Cl)=C1 BOXBZVMLJCORGG-UHFFFAOYSA-N 0.000 description 1
- PRGQEQQILDABPD-UHFFFAOYSA-N 4-(4-amino-3-methylphenoxy)-n-(3-methoxyphenyl)pyrimidin-2-amine Chemical compound COC1=CC=CC(NC=2N=C(OC=3C=C(C)C(N)=CC=3)C=CN=2)=C1 PRGQEQQILDABPD-UHFFFAOYSA-N 0.000 description 1
- TZQQMAAIUGXHDI-UHFFFAOYSA-N 4-(4-amino-3-methylphenoxy)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(OC=2C=C(C)C(N)=CC=2)=N1 TZQQMAAIUGXHDI-UHFFFAOYSA-N 0.000 description 1
- PRIMSUJUKMYIQS-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1C(F)(F)F PRIMSUJUKMYIQS-UHFFFAOYSA-N 0.000 description 1
- IQDBHROKKUGDIZ-UHFFFAOYSA-N 4-(4-piperidin-1-ylpiperidin-1-yl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1N1CCC(N2CCCCC2)CC1 IQDBHROKKUGDIZ-UHFFFAOYSA-N 0.000 description 1
- YTEHESZLVVPXDZ-UHFFFAOYSA-N 4-(azetidin-1-ylmethyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1CN1CCC1 YTEHESZLVVPXDZ-UHFFFAOYSA-N 0.000 description 1
- QPCAOPCOKYWHHQ-UHFFFAOYSA-N 4-(diethylaminomethyl)-3-(trifluoromethyl)aniline Chemical compound CCN(CC)CC1=CC=C(N)C=C1C(F)(F)F QPCAOPCOKYWHHQ-UHFFFAOYSA-N 0.000 description 1
- XJQAPCVYZHUIGD-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1CN1CCOCC1 XJQAPCVYZHUIGD-UHFFFAOYSA-N 0.000 description 1
- ADDKHJPCEFGNAF-UHFFFAOYSA-N 4-[(1-methylpiperidin-4-yl)methoxy]-3-(trifluoromethyl)aniline Chemical compound C1CN(C)CCC1COC1=CC=C(N)C=C1C(F)(F)F ADDKHJPCEFGNAF-UHFFFAOYSA-N 0.000 description 1
- ZYWCDXFRHUHFNV-UHFFFAOYSA-N 4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)aniline Chemical compound C1CN(CC)CCN1CC1=CC=C(N)C=C1C(F)(F)F ZYWCDXFRHUHFNV-UHFFFAOYSA-N 0.000 description 1
- VVTIATCVLPUOPW-UHFFFAOYSA-N 4-[(4-ethylpiperazin-1-yl)methyl]aniline Chemical compound C1CN(CC)CCN1CC1=CC=C(N)C=C1 VVTIATCVLPUOPW-UHFFFAOYSA-N 0.000 description 1
- OGNBIIYVUQZZMZ-UHFFFAOYSA-N 4-[(4-tert-butylpiperazin-1-yl)methyl]-3-(trifluoromethyl)aniline Chemical compound C1CN(C(C)(C)C)CCN1CC1=CC=C(N)C=C1C(F)(F)F OGNBIIYVUQZZMZ-UHFFFAOYSA-N 0.000 description 1
- QAPJFELJRQKLCP-UHFFFAOYSA-N 4-[4-(2,2-dimethylpropyl)piperazin-1-yl]-3-(trifluoromethyl)aniline Chemical compound C1CN(CC(C)(C)C)CCN1C1=CC=C(N)C=C1C(F)(F)F QAPJFELJRQKLCP-UHFFFAOYSA-N 0.000 description 1
- HTNYYXSSFXAJQO-UHFFFAOYSA-N 4-[[6-(4-aminophenoxy)pyrimidin-4-yl]amino]cyclohexan-1-ol Chemical compound C1=CC(N)=CC=C1OC1=CC(NC2CCC(O)CC2)=NC=N1 HTNYYXSSFXAJQO-UHFFFAOYSA-N 0.000 description 1
- GEGHSPMNCRNJJY-UHFFFAOYSA-N 4-[[6-(4-nitrophenoxy)pyrimidin-4-yl]amino]cyclohexan-1-ol Chemical compound C1CC(O)CCC1NC1=CC(OC=2C=CC(=CC=2)[N+]([O-])=O)=NC=N1 GEGHSPMNCRNJJY-UHFFFAOYSA-N 0.000 description 1
- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- YGNISOAUPSJDJE-UHFFFAOYSA-N 4-bromo-3-(trifluoromethyl)aniline Chemical compound NC1=CC=C(Br)C(C(F)(F)F)=C1 YGNISOAUPSJDJE-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WRKWRSUBQVBAQB-UHFFFAOYSA-N 4-morpholin-4-yl-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1N1CCOCC1 WRKWRSUBQVBAQB-UHFFFAOYSA-N 0.000 description 1
- BPCKZQCTLCTDST-UHFFFAOYSA-N 4-nitro-2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1C(F)(F)F BPCKZQCTLCTDST-UHFFFAOYSA-N 0.000 description 1
- ZEFMBAFMCSYJOO-UHFFFAOYSA-N 4-nitro-3-(trifluoromethyl)phenol Chemical compound OC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 ZEFMBAFMCSYJOO-UHFFFAOYSA-N 0.000 description 1
- PIIZYNQECPTVEO-UHFFFAOYSA-N 4-nitro-m-cresol Chemical compound CC1=CC(O)=CC=C1[N+]([O-])=O PIIZYNQECPTVEO-UHFFFAOYSA-N 0.000 description 1
- UGRNAAOSAUZBIT-UHFFFAOYSA-N 4-propan-2-ylpiperazine-1-carbaldehyde Chemical compound CC(C)N1CCN(C=O)CC1 UGRNAAOSAUZBIT-UHFFFAOYSA-N 0.000 description 1
- WBSMIPLNPSCJFS-UHFFFAOYSA-N 5-chloro-2-methoxyaniline Chemical compound COC1=CC=C(Cl)C=C1N WBSMIPLNPSCJFS-UHFFFAOYSA-N 0.000 description 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- KTYPESCCLHWTAJ-UHFFFAOYSA-N 6-(4-aminophenoxy)-n-(3-methoxyphenyl)pyrimidin-4-amine Chemical compound COC1=CC=CC(NC=2N=CN=C(OC=3C=CC(N)=CC=3)C=2)=C1 KTYPESCCLHWTAJ-UHFFFAOYSA-N 0.000 description 1
- KVLGPVUVQGKLDH-UHFFFAOYSA-N 6-(4-aminophenoxy)pyrimidin-4-amine Chemical compound C1=CC(N)=CC=C1OC1=CC(N)=NC=N1 KVLGPVUVQGKLDH-UHFFFAOYSA-N 0.000 description 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QAYNSPOKTRVZRC-UHFFFAOYSA-N 99-60-5 Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1Cl QAYNSPOKTRVZRC-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 101001074560 Arabidopsis thaliana Aquaporin PIP1-2 Proteins 0.000 description 1
- 101001084693 Arabidopsis thaliana Histone H2B.11 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 108091028026 C-DNA Proteins 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- HQWSGAOGGPZFAS-UHFFFAOYSA-N CC(C)(C)[Si+](C)(C)Oc(cc1)ccc1Nc1cc(Oc(cc2)ccc2NC(Nc2cc(C(F)(F)F)cc(C(N)=O)c2)=O)ncn1 Chemical compound CC(C)(C)[Si+](C)(C)Oc(cc1)ccc1Nc1cc(Oc(cc2)ccc2NC(Nc2cc(C(F)(F)F)cc(C(N)=O)c2)=O)ncn1 HQWSGAOGGPZFAS-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
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
- QIVZFPOFNDUWCS-UHFFFAOYSA-N Cc1cc(Oc2nc(Nc3cccc(OC)c3)ncc2)ccc1[N+]([O-])=O Chemical compound Cc1cc(Oc2nc(Nc3cccc(OC)c3)ncc2)ccc1[N+]([O-])=O QIVZFPOFNDUWCS-UHFFFAOYSA-N 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
- UKCVAQGKEOJTSR-UHFFFAOYSA-N Fadrozole hydrochloride Chemical compound Cl.C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 UKCVAQGKEOJTSR-UHFFFAOYSA-N 0.000 description 1
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 description 1
- 102000007317 Farnesyltranstransferase Human genes 0.000 description 1
- 108010007508 Farnesyltranstransferase Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 102100029974 GTPase HRas Human genes 0.000 description 1
- 101710091881 GTPase HRas Proteins 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 1
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010073069 Hepatic cancer Diseases 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- HLXWPURAVKUANR-UHFFFAOYSA-N N-[4-(bromomethyl)-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound BrCC1=C(C=C(C=C1)NC(C(F)(F)F)=O)C(F)(F)F.FC(C(=O)NC1=CC(=C(C=C1)CN1CCN(CC1)CC)C(F)(F)F)(F)F HLXWPURAVKUANR-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- RTAWRZWNPHAUPR-UHFFFAOYSA-N NC=1C=CC(=C(C1)C(F)(F)F)Br.ClC=1C=C(C=CC1)C1=C(C=C(C=C1)N)C(F)(F)F Chemical compound NC=1C=CC(=C(C1)C(F)(F)F)Br.ClC=1C=C(C=CC1)C1=C(C=C(C=C1)N)C(F)(F)F RTAWRZWNPHAUPR-UHFFFAOYSA-N 0.000 description 1
- GPVKLYONJSSZFL-UHFFFAOYSA-N NSC 750259 Natural products CCC(C)C=CC(O)C(O)C(O)C(OC)C(=O)NC1CCCCNC1=O GPVKLYONJSSZFL-UHFFFAOYSA-N 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- MBJMCOJMDMARNB-UHFFFAOYSA-N O.O.O.O.[Na].[Na].OP(O)(=O)C(Cl)(Cl)P(O)(O)=O Chemical compound O.O.O.O.[Na].[Na].OP(O)(=O)C(Cl)(Cl)P(O)(O)=O MBJMCOJMDMARNB-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- 108010045292 Proto-Oncogene Proteins c-abl Proteins 0.000 description 1
- 102000005663 Proto-Oncogene Proteins c-abl Human genes 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 229940078123 Ras inhibitor Drugs 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 102000038012 SFKs Human genes 0.000 description 1
- 108091008118 SFKs Proteins 0.000 description 1
- 102000000395 SH3 domains Human genes 0.000 description 1
- 108050008861 SH3 domains Proteins 0.000 description 1
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 1
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 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
- 229920001615 Tragacanth Polymers 0.000 description 1
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 201000003761 Vaginal carcinoma Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- GJWAPAVRQYYSTK-UHFFFAOYSA-N [(dimethyl-$l^{3}-silanyl)amino]-dimethylsilicon Chemical compound C[Si](C)N[Si](C)C GJWAPAVRQYYSTK-UHFFFAOYSA-N 0.000 description 1
- VJUZHVZUKUFLLA-UHFFFAOYSA-N [3-amino-5-(trifluoromethyl)phenyl]-(4-propan-2-ylpiperazin-1-yl)methanone Chemical compound C1CN(C(C)C)CCN1C(=O)C1=CC(N)=CC(C(F)(F)F)=C1 VJUZHVZUKUFLLA-UHFFFAOYSA-N 0.000 description 1
- UBKLYXCZJYWYLX-UHFFFAOYSA-N [3-amino-5-(trifluoromethyl)phenyl]-(azetidin-1-yl)methanone Chemical compound FC(F)(F)C1=CC(N)=CC(C(=O)N2CCC2)=C1 UBKLYXCZJYWYLX-UHFFFAOYSA-N 0.000 description 1
- WTDRPWBCDQCTOV-UHFFFAOYSA-N [3-nitro-5-(trifluoromethyl)phenyl]-(4-propan-2-ylpiperazin-1-yl)methanone Chemical compound C1CN(C(C)C)CCN1C(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 WTDRPWBCDQCTOV-UHFFFAOYSA-N 0.000 description 1
- MFOSAHLGQDMTAV-UHFFFAOYSA-N [4-amino-2-(trifluoromethyl)phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(N)C=C1C(F)(F)F MFOSAHLGQDMTAV-UHFFFAOYSA-N 0.000 description 1
- QPMSXSBEVQLBIL-CZRHPSIPSA-N ac1mix0p Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1.O([C@H]1[C@]2(OC)C=CC34C[C@@H]2[C@](C)(O)CCC)C2=C5[C@]41CCN(C)[C@@H]3CC5=CC=C2O QPMSXSBEVQLBIL-CZRHPSIPSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229940037127 actonel Drugs 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 201000005179 adrenal carcinoma Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229940110282 alimta Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000006319 alkynyl amino group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 1
- 229960005471 androstenedione Drugs 0.000 description 1
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000009949 anti-apoptotic pathway Effects 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000005735 apoptotic response Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000004104 aryloxy group Chemical group 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
- 230000035578 autophosphorylation Effects 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- JXPGPTHWVCKRFI-UHFFFAOYSA-N azetidin-1-yl-[3-nitro-5-(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC([N+](=O)[O-])=CC(C(=O)N2CCC2)=C1 JXPGPTHWVCKRFI-UHFFFAOYSA-N 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 1
- 229940116226 behenic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- CQXLSHXFWSFOKF-UHFFFAOYSA-N benzoyl 4-[[4-[(2,2,2-trifluoroacetyl)amino]-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound FC(F)(F)C1=CC(NC(=O)C(F)(F)F)=CC=C1CN1CCN(C(=O)OC(=O)C=2C=CC=CC=2)CC1 CQXLSHXFWSFOKF-UHFFFAOYSA-N 0.000 description 1
- BMALKGXGERYRCJ-UHFFFAOYSA-N benzoyl 4-[[4-[[4-(6-azidopyrimidin-4-yl)oxyphenyl]carbamoylamino]-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound C=1C=C(CN2CCN(CC2)C(=O)OC(=O)C=2C=CC=CC=2)C(C(F)(F)F)=CC=1NC(=O)NC(C=C1)=CC=C1OC1=CC(N=[N+]=[N-])=NC=N1 BMALKGXGERYRCJ-UHFFFAOYSA-N 0.000 description 1
- PNWPORCVWVAOKU-UHFFFAOYSA-N benzyl 4-[[4-[(2,2,2-trifluoroacetyl)amino]-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate Chemical compound FC(F)(F)C1=CC(NC(=O)C(F)(F)F)=CC=C1CN1CCN(C(=O)OCC=2C=CC=CC=2)CC1 PNWPORCVWVAOKU-UHFFFAOYSA-N 0.000 description 1
- CTOUWUYDDUSBQE-UHFFFAOYSA-N benzyl piperazine-1-carboxylate Chemical compound C1CNCCN1C(=O)OCC1=CC=CC=C1 CTOUWUYDDUSBQE-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical compound ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229940088954 camptosar Drugs 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
- 229960004117 capecitabine Drugs 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- MLIFNJABMANKEU-UHFFFAOYSA-N cep-5214 Chemical compound C1=CC=C2C3=C(C(=O)NC4)C4=C(C=4C(=CC=C(C=4)COC(C)C)N4CCCO)C4=C3CC2=C1 MLIFNJABMANKEU-UHFFFAOYSA-N 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 201000002797 childhood leukemia Diseases 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 208000023819 chronic asthma Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 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
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 230000009668 clonal growth Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004465 cycloalkenyloxy group Chemical group 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 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
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 229940026692 decadron Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 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
- UKWLRLAKGMZXJC-QIECWBMSSA-L disodium;[4-chloro-3-[(3r,5s)-1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl]phenyl] phosphate Chemical compound [Na+].[Na+].O1OC2([C@@H]3CC4C[C@H]2CC(Cl)(C4)C3)C1(OC)C1=CC(OP([O-])([O-])=O)=CC=C1Cl UKWLRLAKGMZXJC-QIECWBMSSA-L 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 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
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229950006700 edatrexate Drugs 0.000 description 1
- FSIRXIHZBIXHKT-MHTVFEQDSA-N edatrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CC(CC)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FSIRXIHZBIXHKT-MHTVFEQDSA-N 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 229940120655 eloxatin Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000009585 enzyme analysis Methods 0.000 description 1
- 229960001433 erlotinib 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
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
- OKOHFSWRKRCHAD-UHFFFAOYSA-N ethane ethanesulfonic acid Chemical compound CC.CCS(O)(=O)=O OKOHFSWRKRCHAD-UHFFFAOYSA-N 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LKVXSBPPCRGKIF-UHFFFAOYSA-N ethyl n,n-bis(2-chloroethyl)carbamate Chemical compound CCOC(=O)N(CCCl)CCCl LKVXSBPPCRGKIF-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 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
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=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 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 229940085363 evista Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 229940087861 faslodex Drugs 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 229940087476 femara Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 229960005304 fludarabine phosphate Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229940001490 fosamax Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960003690 goserelin acetate Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 208000021991 hereditary neoplastic syndrome Diseases 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- 208000027706 hormone receptor-positive breast cancer Diseases 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229940088013 hycamtin Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[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](CC=4C=CC=CC=4)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)NC2=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](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=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)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 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
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- UHEBDUAFKQHUBV-UHFFFAOYSA-N jspy-st000261 Chemical compound C1=CC=C2C3=C(C(=O)NC4)C4=C(C=4C(=CC=C(C=4)COC(C)C)N4CCCOC(=O)CN(C)C)C4=C3CC2=C1 UHEBDUAFKQHUBV-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000002250 liver carcinoma Diseases 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000011147 magnesium chloride Nutrition 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 201000005282 malignant pleural mesothelioma Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 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
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- QEIDSSLUKKFBCE-UHFFFAOYSA-N methane;methanesulfonic acid Chemical compound C.CS(O)(=O)=O QEIDSSLUKKFBCE-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- PYZLRNMGUBDIHK-UHFFFAOYSA-N molecular hydrogen;nickel Chemical compound [Ni].[H][H] PYZLRNMGUBDIHK-UHFFFAOYSA-N 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- GCOWZPRIMFGIDQ-UHFFFAOYSA-N n',n'-dimethylbutane-1,4-diamine Chemical compound CN(C)CCCCN GCOWZPRIMFGIDQ-UHFFFAOYSA-N 0.000 description 1
- ZQGJEUVBUVKZKS-UHFFFAOYSA-N n,2-dimethylpropan-2-amine Chemical compound CNC(C)(C)C ZQGJEUVBUVKZKS-UHFFFAOYSA-N 0.000 description 1
- GFKMLCUUUKJZLQ-UHFFFAOYSA-N n,n-diethyl-3-nitro-5-(trifluoromethyl)benzamide Chemical compound CCN(CC)C(=O)C1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 GFKMLCUUUKJZLQ-UHFFFAOYSA-N 0.000 description 1
- LLYKPZOWCPVRPD-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine;n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=CC=N1 LLYKPZOWCPVRPD-UHFFFAOYSA-N 0.000 description 1
- SLFVYFOEHHLHDW-UHFFFAOYSA-N n-(trifluoromethyl)aniline Chemical compound FC(F)(F)NC1=CC=CC=C1 SLFVYFOEHHLHDW-UHFFFAOYSA-N 0.000 description 1
- BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=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 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- ISIMZYOUKJSQLA-UHFFFAOYSA-N n-[4-(4-amino-3-methylphenoxy)pyrimidin-2-yl]-n',n'-dimethylbutane-1,4-diamine Chemical compound CN(C)CCCCNC1=NC=CC(OC=2C=C(C)C(N)=CC=2)=N1 ISIMZYOUKJSQLA-UHFFFAOYSA-N 0.000 description 1
- FLABRAILTQUHKU-UHFFFAOYSA-N n-[4-(azetidin-1-ylmethyl)-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound FC(F)(F)C1=CC(NC(=O)C(F)(F)F)=CC=C1CN1CCC1 FLABRAILTQUHKU-UHFFFAOYSA-N 0.000 description 1
- GRYJCHDQOHMZKY-UHFFFAOYSA-N n-[4-[(4-tert-butylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound C1CN(C(C)(C)C)CCN1CC1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F GRYJCHDQOHMZKY-UHFFFAOYSA-N 0.000 description 1
- WDDMWAZBBUIRHW-UHFFFAOYSA-N n-[4-[4-[[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyrimidin-2-yl]acetamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC(NC(C)=O)=N1 WDDMWAZBBUIRHW-UHFFFAOYSA-N 0.000 description 1
- OBWTWHZFARPSJU-UHFFFAOYSA-N n-[4-[[4-(2,2-dimethylpropyl)piperazin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound C1CN(CC(C)(C)C)CCN1CC1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F OBWTWHZFARPSJU-UHFFFAOYSA-N 0.000 description 1
- SZKQWOIMNMUVTJ-UHFFFAOYSA-N n-[6-[4-[[4-morpholin-4-yl-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyrimidin-4-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(N4CCOCC4)=CC=3)C(F)(F)F)=CC=2)=N1 SZKQWOIMNMUVTJ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229950010159 nemorubicin Drugs 0.000 description 1
- CTMCWCONSULRHO-UHQPFXKFSA-N nemorubicin Chemical compound C1CO[C@H](OC)CN1[C@@H]1[C@H](O)[C@H](C)O[C@@H](O[C@@H]2C3=C(O)C=4C(=O)C5=C(OC)C=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)C1 CTMCWCONSULRHO-UHQPFXKFSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 239000003076 neurotropic agent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- FPOHNWQLNRZRFC-ZHACJKMWSA-N panobinostat Chemical compound CC=1NC2=CC=CC=C2C=1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FPOHNWQLNRZRFC-ZHACJKMWSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical class [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical group N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 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
- 229960004622 raloxifene Drugs 0.000 description 1
- 229940099538 rapamune Drugs 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 208000020615 rectal carcinoma Diseases 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- 229950009213 rubitecan Drugs 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229940112726 skelid Drugs 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical class C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000005338 substituted cycloalkoxy group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 1
- 229950007866 tanespimycin Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 229960001674 tegafur Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- HZPQJOQYIREUHZ-UHFFFAOYSA-N tert-butyl n-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]carbamate Chemical compound C1CN(C)CCN1C1=CC(NC(=O)OC(C)(C)C)=CC(C(F)(F)F)=C1 HZPQJOQYIREUHZ-UHFFFAOYSA-N 0.000 description 1
- PGCWCIPXTAAMTC-UHFFFAOYSA-N tert-butyl n-[3-bromo-5-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Br)=CC(C(F)(F)F)=C1 PGCWCIPXTAAMTC-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 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
- 238000010257 thawing Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CFQJBWKKHCMCGJ-UHFFFAOYSA-N tributyl(pyridin-3-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CN=C1 CFQJBWKKHCMCGJ-UHFFFAOYSA-N 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006459 vascular development Effects 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine 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-CFWMRBGOSA-N 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
- 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
- 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
- 229940087652 vioxx Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
- 229940033942 zoladex Drugs 0.000 description 1
- 229940002005 zometa Drugs 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Inorganic Chemistry (AREA)
- Structural Engineering (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0327734A GB0327734D0 (en) | 2003-11-28 | 2003-11-28 | Organic compounds |
| GB0417805A GB0417805D0 (en) | 2004-08-10 | 2004-08-10 | Organic compounds |
| PCT/EP2004/013459 WO2005051366A2 (en) | 2003-11-28 | 2004-11-26 | Diaryl urea derivatives in the treatment of protein kinase dependent diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007515400A true JP2007515400A (ja) | 2007-06-14 |
| JP2007515400A5 JP2007515400A5 (https=) | 2008-01-17 |
Family
ID=34635447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006540401A Ceased JP2007515400A (ja) | 2003-11-28 | 2004-11-26 | タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20080312192A1 (https=) |
| EP (1) | EP1689376A2 (https=) |
| JP (1) | JP2007515400A (https=) |
| KR (1) | KR20060110307A (https=) |
| AR (1) | AR047496A1 (https=) |
| AU (2) | AU2004292773A1 (https=) |
| BR (1) | BRPI0416935A (https=) |
| CA (1) | CA2546673A1 (https=) |
| PE (1) | PE20051046A1 (https=) |
| RU (1) | RU2006122853A (https=) |
| TW (1) | TW200529849A (https=) |
| WO (1) | WO2005051366A2 (https=) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011500685A (ja) * | 2007-10-19 | 2011-01-06 | アビラ セラピューティクス， インコーポレイテッド | ヘテロアリール化合物およびその使用 |
| JP2012524123A (ja) * | 2009-04-20 | 2012-10-11 | アビラ セラピューティクス， インコーポレイテッド | へテロアリール化合物およびその使用 |
| JP2012526054A (ja) * | 2009-05-05 | 2012-10-25 | 江▲蘇▼省▲薬▼物研究所有限公司 | 複素環置換のジフェニル尿素類誘導体及びその用途 |
| JP2015525739A (ja) * | 2012-06-26 | 2015-09-07 | クラウン バイオサイエンス インコーポレイテッド（台湾） | 抗癌剤であるシクロプロパンカルボキサミドで置換された芳香族化合物 |
| JP2017535525A (ja) * | 2014-10-01 | 2017-11-30 | レスピバート・リミテツド | Ｐ３８キナーゼ阻害剤としてのジアリール尿素誘導体 |
| JP2021506935A (ja) * | 2017-12-21 | 2021-02-22 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU9598601A (en) | 2000-10-20 | 2002-04-29 | Eisai Co Ltd | Nitrogenous aromatic ring compounds |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| HRP20050089B1 (hr) | 2002-07-29 | 2015-06-19 | Rigel Pharmaceuticals | Upotreba 2,4 pirimidindiaminskog spoja za proizvodnju lijeka za lijeäśenje ili sprjeäśavanje autoimunosne bolesti |
| ATE508747T1 (de) | 2003-03-10 | 2011-05-15 | Eisai R&D Man Co Ltd | C-kit kinase-hemmer |
| WO2005012294A1 (en) | 2003-07-30 | 2005-02-10 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases |
| US7683172B2 (en) | 2003-11-11 | 2010-03-23 | Eisai R&D Management Co., Ltd. | Urea derivative and process for preparing the same |
| ES2522579T3 (es) | 2004-06-17 | 2014-11-17 | Cytokinetics, Inc. | Compuestos, composiciones y métodos |
| AU2011253934C1 (en) * | 2004-06-17 | 2013-08-22 | Cytokinetics, Inc. | Substituted urea derivatives for treating cardiac diseases |
| GB0512324D0 (en) * | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| ATE428421T1 (de) | 2004-09-17 | 2009-05-15 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
| AU2006206458B2 (en) | 2005-01-19 | 2012-10-25 | Rigel Pharmaceuticals, Inc. | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
| BRPI0610876B8 (pt) | 2005-06-08 | 2021-05-25 | Rigel Pharmaceuticals Inc | composto, formulação farmacêutica, e métodos de inibir uma atividade de uma jak cinase, e de inibir uma cascata de transdução de sinal em que jak3 cinase desempenha um papel |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| JP4989476B2 (ja) | 2005-08-02 | 2012-08-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質の効果を検定する方法 |
| ES2419007T3 (es) | 2005-12-15 | 2013-08-19 | Cytokinetics, Inc. | Ciertas entidades químicas, composiciones y procedimientos |
| WO2007078839A2 (en) | 2005-12-19 | 2007-07-12 | Cytokinetics, Inc. | Compounds, compositions and methods |
| GEP20105074B (en) | 2005-12-21 | 2010-09-10 | Novartis Ag | Pyrimidinyl aryl urea derivatives being fgf inhibitors |
| TW200804349A (en) * | 2005-12-23 | 2008-01-16 | Kalypsys Inc | Novel substituted pyrimidinyloxy ureas as inhibitors of protein kinases |
| EA034598B1 (ru) | 2005-12-23 | 2020-02-25 | Ариад Фармасьютикалз, Инк. | Применение бициклических гетероарильных соединений для лечения рака |
| ES2622493T3 (es) | 2006-02-24 | 2017-07-06 | Rigel Pharmaceuticals, Inc. | Composiciones y métodos para la inhibición de la ruta de JAK |
| GB0605120D0 (en) | 2006-03-14 | 2006-04-26 | Novartis Ag | Organic 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 |
| CN104706637A (zh) * | 2006-05-18 | 2015-06-17 | 卫材R&D管理有限公司 | 针对甲状腺癌的抗肿瘤剂 |
| EP2543739B1 (en) * | 2006-08-11 | 2015-07-22 | Johns Hopkins University | Consensus coding sequences of human colorectal cancers |
| WO2008026748A1 (en) | 2006-08-28 | 2008-03-06 | Eisai R & D Management Co., Ltd. | Antitumor agent for undifferentiated gastric cancer |
| AU2013231117B2 (en) * | 2006-12-14 | 2016-06-02 | Janssen Pharmaceutica N.V. | Process for the preparation of piperazinyl and diazepanyl benzamide derivatives |
| DE602007010038D1 (de) | 2006-12-22 | 2010-12-02 | Hoffmann La Roche | Pyrimidylderivate als proteinkinaseinhibitoren |
| CA2676796C (en) | 2007-01-29 | 2016-02-23 | Eisai R & D Management Co., Ltd. | Composition for treatment of undifferentiated gastric cancer |
| GB0706932D0 (en) * | 2007-04-10 | 2007-05-16 | Univ London Pharmacy | Ureylene derivatives |
| CA2683049A1 (en) | 2007-04-17 | 2008-10-23 | Novartis Ag | Organic compounds |
| FR2921657A1 (fr) * | 2007-09-28 | 2009-04-03 | Sanofi Aventis Sa | Derives de nicotinamide, leur preparation et leur application en therapeutique |
| US8952035B2 (en) | 2007-11-09 | 2015-02-10 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| EP2070929A1 (en) | 2007-12-11 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Alkynylaryl compounds and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| JP2011520809A (ja) * | 2008-05-05 | 2011-07-21 | アムジエン・インコーポレーテツド | γセクレターゼモジュレーターとしての尿素化合物 |
| FR2943669B1 (fr) * | 2009-03-24 | 2011-05-06 | Sanofi Aventis | Derives de nicotinamide,leur preparation et leur application en therapeutique |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| MY162940A (en) | 2009-08-19 | 2017-07-31 | Eisai R&D Man Co Ltd | Quinoline derivative-containing pharmaceutical composition |
| ME03376B (me) | 2010-05-20 | 2020-01-20 | Array Biopharma Inc | Makrociklička jedinjenja kао inhibiтori trk kinaze |
| CN102958523B (zh) | 2010-06-25 | 2014-11-19 | 卫材R&D管理有限公司 | 使用具有激酶抑制作用的组合的抗肿瘤剂 |
| FR2965263A1 (fr) | 2010-09-24 | 2012-03-30 | Sanofi Aventis | Derives de thienopyridine nicotinamide, leur preparation et leur application en therapeutique |
| FR2965262A1 (fr) | 2010-09-24 | 2012-03-30 | Sanofi Aventis | Derives de nicotinamide, leur preparation et leur application en therapeutique |
| CN103402519B (zh) | 2011-04-18 | 2015-11-25 | 卫材R&D管理有限公司 | 肿瘤治疗剂 |
| JP6038128B2 (ja) | 2011-06-03 | 2016-12-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する甲状腺癌対象及び腎臓癌対象の反応性を予測及び評価するためのバイオマーカー |
| EP2760843B1 (en) * | 2011-09-26 | 2016-03-02 | Bristol-Myers Squibb Company | Selective nr2b antagonists |
| 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 |
| KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
| AU2014246866B2 (en) | 2013-04-02 | 2018-05-10 | Oxular Acquisitions Limited | Kinase inhibitor |
| NZ714049A (en) | 2013-05-14 | 2020-05-29 | Eisai R&D Man Co Ltd | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| CA2934199A1 (en) * | 2013-12-20 | 2015-06-25 | Respivert Limited | Urea derivatives useful as kinase inhibitors |
| PT3524595T (pt) | 2014-08-28 | 2022-09-19 | Eisai R&D Man Co Ltd | Derivado de quinolina altamente puro e método para produção do mesmo |
| CN113354649B (zh) | 2014-11-16 | 2024-12-10 | 阵列生物制药公司 | 一种新的晶型 |
| LT3263106T (lt) | 2015-02-25 | 2024-01-10 | Eisai R&D Management Co., Ltd. | Chinolino darinių kartumo sumažinimo būdas |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| MX373231B (es) | 2015-06-16 | 2020-05-08 | Eisai R&D Man Co Ltd | Agente anticancerigeno. |
| BR112018000808A2 (pt) | 2015-07-16 | 2018-09-04 | Array Biopharma Inc | compostos de pirazolo[1,5-a]piridina substituída como inibidores de ret cinase |
| US12220398B2 (en) | 2015-08-20 | 2025-02-11 | Eisai R&D Management Co., Ltd. | Tumor therapeutic agent |
| EP3368039A1 (en) | 2015-10-26 | 2018-09-05 | The Regents of The University of Colorado, A Body Corporate | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| FI3439662T3 (fi) | 2016-04-04 | 2024-09-04 | Loxo Oncology Inc | (s)-n-(5-((r)-2-(2,5-difluorifenyyli)pyrrolidin-1-yyli)pyratsolo[1,5-a]pyrimidin-3-yyli)-3-hydroksipyrrolidiini-1-karboksamidin nesteformulaatioita |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| AU2017246547B2 (en) | 2016-04-04 | 2023-02-23 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| EP3458456B1 (en) | 2016-05-18 | 2020-11-25 | Loxo Oncology Inc. | Preparation of (s)-n-(5-((r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| TWI752098B (zh) | 2016-10-10 | 2022-01-11 | 美商亞雷生物製藥股份有限公司 | 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| WO2018136661A1 (en) | 2017-01-18 | 2018-07-26 | Andrews Steven W | SUBSTITUTED PYRAZOLO[1,5-a]PYRAZINE COMPOUNDS AS RET KINASE INHIBITORS |
| US12303505B2 (en) | 2017-02-08 | 2025-05-20 | Eisai R&D Management Co., Ltd. | Tumor-treating pharmaceutical composition |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| RU2019134940A (ru) | 2017-05-16 | 2021-06-16 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Лечение гепатоцеллюлярной карциномы |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| EP3740490A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| US11472802B2 (en) | 2018-01-18 | 2022-10-18 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridine compounds as RET kinase inhibitors |
| JP7060694B2 (ja) | 2018-01-18 | 2022-04-26 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての置換ピロロ［２，３－ｄ］ピリミジン化合物 |
| CN112996794A (zh) | 2018-09-10 | 2021-06-18 | 阿雷生物药品公司 | 作为ret激酶抑制剂的稠合杂环化合物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000042012A1 (en) * | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| JP2006528196A (ja) * | 2003-07-23 | 2006-12-14 | バイエル、ファーマシューテイカルズ、コーポレイション | 病気および状態の処置および防止のためのフロロ置換オメガカルボキシアリールジフェニル尿素 |
| JP2007511203A (ja) * | 2003-05-20 | 2007-05-10 | バイエル、ファーマシューテイカルズ、コーポレイション | キナーゼ阻害活性を有するジアリール尿素 |
| JP4608312B2 (ja) * | 2002-05-29 | 2011-01-12 | ノバルティス アーゲー | プロテインキナーゼ依存性疾患の処置に有用なジアリールウレア誘導体 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU594098B2 (en) * | 1985-12-11 | 1990-03-01 | Ishihara Sangyo Kaisha Ltd. | N-benzoyl urea compounds, antitumorous compositions containing them, and process for their preparation |
| WO1999032463A1 (en) * | 1997-12-22 | 1999-07-01 | Bayer Corporation | INHIBITION OF p38 KINASE USING SYMMETRICAL AND UNSYMMETRICAL DIPHENYL UREAS |
| US7928239B2 (en) * | 1999-01-13 | 2011-04-19 | Bayer Healthcare Llc | Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas |
| AU9598601A (en) * | 2000-10-20 | 2002-04-29 | Eisai Co Ltd | Nitrogenous aromatic ring compounds |
| AU2002340139A1 (en) * | 2001-10-09 | 2003-04-22 | The University Of Cincinnati | Inhibitors of the egf receptor for the treatment of thyroid cancer |
| SI1478358T1 (sl) * | 2002-02-11 | 2013-09-30 | Bayer Healthcare Llc | Sorafenib tozilat za zdravljenje bolezni, značilnih po abnormalni angiogenezi |
-
2004
- 2004-11-26 PE PE2004001167A patent/PE20051046A1/es not_active Application Discontinuation
- 2004-11-26 KR KR1020067010328A patent/KR20060110307A/ko not_active Ceased
- 2004-11-26 RU RU2006122853/04A patent/RU2006122853A/ru unknown
- 2004-11-26 CA CA002546673A patent/CA2546673A1/en not_active Abandoned
- 2004-11-26 US US10/580,259 patent/US20080312192A1/en not_active Abandoned
- 2004-11-26 WO PCT/EP2004/013459 patent/WO2005051366A2/en not_active Ceased
- 2004-11-26 BR BRPI0416935-2A patent/BRPI0416935A/pt not_active IP Right Cessation
- 2004-11-26 JP JP2006540401A patent/JP2007515400A/ja not_active Ceased
- 2004-11-26 AU AU2004292773A patent/AU2004292773A1/en not_active Abandoned
- 2004-11-26 TW TW093136547A patent/TW200529849A/zh unknown
- 2004-11-26 EP EP04798101A patent/EP1689376A2/en not_active Withdrawn
- 2004-11-26 AR ARP040104414A patent/AR047496A1/es unknown
-
2009
- 2009-07-30 AU AU2009203096A patent/AU2009203096A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000042012A1 (en) * | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| JP4608312B2 (ja) * | 2002-05-29 | 2011-01-12 | ノバルティス アーゲー | プロテインキナーゼ依存性疾患の処置に有用なジアリールウレア誘導体 |
| JP2007511203A (ja) * | 2003-05-20 | 2007-05-10 | バイエル、ファーマシューテイカルズ、コーポレイション | キナーゼ阻害活性を有するジアリール尿素 |
| JP2006528196A (ja) * | 2003-07-23 | 2006-12-14 | バイエル、ファーマシューテイカルズ、コーポレイション | 病気および状態の処置および防止のためのフロロ置換オメガカルボキシアリールジフェニル尿素 |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011500685A (ja) * | 2007-10-19 | 2011-01-06 | アビラ セラピューティクス， インコーポレイテッド | ヘテロアリール化合物およびその使用 |
| US8748606B2 (en) | 2007-10-19 | 2014-06-10 | Celgene Avilomics Research, Inc. | 4,6-diaminopyrimidines useful as kinase inhibitors |
| US9040541B2 (en) | 2007-10-19 | 2015-05-26 | Celgene Avilomics Research, Inc. | 4,6-disubstituted pyrimidines useful as kinase inhibitors |
| US9393246B2 (en) | 2007-10-19 | 2016-07-19 | Celgene Avilomics Research, Inc. | 4,6-disubstituted pyrimidines as kinase inhibitors |
| JP2012524123A (ja) * | 2009-04-20 | 2012-10-11 | アビラ セラピューティクス， インコーポレイテッド | へテロアリール化合物およびその使用 |
| JP2012526054A (ja) * | 2009-05-05 | 2012-10-25 | 江▲蘇▼省▲薬▼物研究所有限公司 | 複素環置換のジフェニル尿素類誘導体及びその用途 |
| JP2015525739A (ja) * | 2012-06-26 | 2015-09-07 | クラウン バイオサイエンス インコーポレイテッド（台湾） | 抗癌剤であるシクロプロパンカルボキサミドで置換された芳香族化合物 |
| JP2017008082A (ja) * | 2012-06-26 | 2017-01-12 | クラウン バイオサイエンス インコーポレイテッド（台湾） | 抗癌剤であるシクロプロパンカルボキサミドで置換された芳香族化合物 |
| JP2017535525A (ja) * | 2014-10-01 | 2017-11-30 | レスピバート・リミテツド | Ｐ３８キナーゼ阻害剤としてのジアリール尿素誘導体 |
| JP2021506935A (ja) * | 2017-12-21 | 2021-02-22 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
| JP7021356B2 (ja) | 2017-12-21 | 2022-02-16 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
| US11602534B2 (en) | 2017-12-21 | 2023-03-14 | Hefei Institutes Of Physical Science, Chinese Academy Of Sciences | Pyrimidine derivative kinase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004292773A1 (en) | 2005-06-09 |
| BRPI0416935A (pt) | 2007-01-16 |
| EP1689376A2 (en) | 2006-08-16 |
| WO2005051366A2 (en) | 2005-06-09 |
| AU2009203096A1 (en) | 2009-08-20 |
| TW200529849A (en) | 2005-09-16 |
| AR047496A1 (es) | 2006-01-25 |
| KR20060110307A (ko) | 2006-10-24 |
| WO2005051366A3 (en) | 2007-12-21 |
| RU2006122853A (ru) | 2008-01-10 |
| PE20051046A1 (es) | 2006-01-11 |
| US20080312192A1 (en) | 2008-12-18 |
| CA2546673A1 (en) | 2005-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2007515400A (ja) | タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 | |
| JP4608312B2 (ja) | プロテインキナーゼ依存性疾患の処置に有用なジアリールウレア誘導体 | |
| JP5153645B2 (ja) | Ｆｇｆ阻害剤であるピリミジニルアリールウレア誘導体 | |
| US7855215B2 (en) | Cyclic diaryl ureas suitable as tyrosine kinase inhibitors | |
| AU2005310968C1 (en) | Bicyclic amides as kinase inhibitors | |
| CN100412066C (zh) | 用作蛋白激酶抑制剂的化合物和组合物 | |
| JP2010524885A (ja) | がん治療剤としてのナフタレンカルボン酸アミドのエーテル | |
| CN101291917A (zh) | 治疗蛋白激酶依赖性疾病的二芳基脲衍生物 | |
| MXPA06006036A (en) | Diaryl urea derivatives in the treatment of protein kinase dependent diseases | |
| HK1151292B (en) | 2,4-diaminopyrimidine derivatives | |
| HK1151292A1 (en) | 2,4-diaminopyrimidine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071115 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071115 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20110404 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110405 |
|
| AA92 | Notification that decision to refuse application was cancelled |
Free format text: JAPANESE INTERMEDIATE CODE: A971092 Effective date: 20110419 |