NZ518028A - Quinazoline derivatives as VEGF inhibitors - Google Patents

Info

Publication number

NZ518028A

NZ518028A NZ518028A NZ51802800A NZ518028A NZ 518028 A NZ518028 A NZ 518028A NZ 518028 A NZ518028 A NZ 518028A NZ 51802800 A NZ51802800 A NZ 51802800A NZ 518028 A NZ518028 A NZ 518028A

Authority

NZ

New Zealand

Prior art keywords

formula

quinazoline

ylmethoxy

methoxy

compound

Prior art date

1999-11-05

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 3
• 239000002525 vasculotropin inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 172
• 150000003839 salts Chemical class 0.000 claims abstract description 76
• 238000000034 method Methods 0.000 claims abstract description 47
• 230000000694 effects Effects 0.000 claims abstract description 27
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract description 25
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 25
• 230000008569 process Effects 0.000 claims abstract description 23
• 125000005843 halogen group Chemical group 0.000 claims abstract description 20
• 125000001424 substituent group Chemical group 0.000 claims abstract description 17
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
• 238000002360 preparation method Methods 0.000 claims abstract description 11
• 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 239000004480 active ingredient Substances 0.000 claims abstract description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims abstract description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 51
• -1 2-fluoro-4-methylphenyl Chemical group 0.000 claims description 46
• 239000000203 mixture Substances 0.000 claims description 35
• 238000006243 chemical reaction Methods 0.000 claims description 32
• 241001465754 Metazoa Species 0.000 claims description 18
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 17
• 230000008728 vascular permeability Effects 0.000 claims description 16
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 150000003246 quinazolines Chemical class 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 14
• 230000001772 anti-angiogenic effect Effects 0.000 claims description 12
• 239000002253 acid Substances 0.000 claims description 11
• 230000001603 reducing effect Effects 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 claims description 8
• 125000006239 protecting group Chemical group 0.000 claims description 7
• KNAJKXGUAHBQTI-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCN(C)CC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F KNAJKXGUAHBQTI-UHFFFAOYSA-N 0.000 claims description 6
• KQEHWOWUWGAOSR-UHFFFAOYSA-N n-(4-chloro-2,6-difluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCN(C)CC3)C(OC)=CC2=C1NC1=C(F)C=C(Cl)C=C1F KQEHWOWUWGAOSR-UHFFFAOYSA-N 0.000 claims description 5
• 125000003386 piperidinyl group Chemical group 0.000 claims description 5
• 238000010511 deprotection reaction Methods 0.000 claims description 4
• 230000005764 inhibitory process Effects 0.000 claims description 4
• PBESGEKOQIKSKI-UHFFFAOYSA-N n-(4-bromo-2,6-difluorophenyl)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCNCC3)C(OC)=CC2=C1NC1=C(F)C=C(Br)C=C1F PBESGEKOQIKSKI-UHFFFAOYSA-N 0.000 claims description 4
• AVQNSHZBOYOSQZ-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCNCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F AVQNSHZBOYOSQZ-UHFFFAOYSA-N 0.000 claims description 4
• KIWKXIDEBINNAK-UHFFFAOYSA-N n-(4-bromo-2,6-difluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCN(C)CC3)C(OC)=CC2=C1NC1=C(F)C=C(Br)C=C1F KIWKXIDEBINNAK-UHFFFAOYSA-N 0.000 claims description 3
• HTCPERSEGREUFC-UHFFFAOYSA-N n-desmethyl vandetanib Chemical compound N1=CN=C2C=C(OCC3CCNCC3)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F HTCPERSEGREUFC-UHFFFAOYSA-N 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 239000004066 vascular targeting agent Substances 0.000 claims description 3
• 239000008215 water for injection Substances 0.000 claims description 3
• 239000011248 coating agent Substances 0.000 claims description 2
• 238000000576 coating method Methods 0.000 claims description 2
• QAWSAMDJZZDGDW-UHFFFAOYSA-N n-(2-fluoro-4-methylphenyl)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCNCC3)C(OC)=CC2=C1NC1=CC=C(C)C=C1F QAWSAMDJZZDGDW-UHFFFAOYSA-N 0.000 claims description 2
• WPCUQWCGLJALCN-UHFFFAOYSA-N n-(2-fluoro-4-methylphenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCN(C)CC3)C(OC)=CC2=C1NC1=CC=C(C)C=C1F WPCUQWCGLJALCN-UHFFFAOYSA-N 0.000 claims description 2
• 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 2
• 229920000623 Cellulose acetate phthalate Polymers 0.000 claims 1
• 230000001093 anti-cancer Effects 0.000 claims 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 238000009472 formulation Methods 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 26
• 238000011282 treatment Methods 0.000 abstract description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
• 201000011510 cancer Diseases 0.000 abstract description 6
• 201000010099 disease Diseases 0.000 abstract description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 126
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
• 239000000243 solution Substances 0.000 description 52
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 47
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 39
• 238000001914 filtration Methods 0.000 description 33
• 239000007787 solid Substances 0.000 description 30
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• 239000003039 volatile agent Substances 0.000 description 26
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 23
• 239000007858 starting material Substances 0.000 description 23
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 238000003756 stirring Methods 0.000 description 21
• 239000000725 suspension Substances 0.000 description 21
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• 238000001704 evaporation Methods 0.000 description 18
• 230000008020 evaporation Effects 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 17
• 239000002244 precipitate Substances 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 238000000921 elemental analysis Methods 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 239000002904 solvent Substances 0.000 description 13
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
• 239000012442 inert solvent Substances 0.000 description 11
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
• 241000700159 Rattus Species 0.000 description 10
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 239000003701 inert diluent Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 102000004190 Enzymes Human genes 0.000 description 9
• 108090000790 Enzymes Proteins 0.000 description 9
• 102400001368 Epidermal growth factor Human genes 0.000 description 9
• 101800003838 Epidermal growth factor Proteins 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• 229940088598 enzyme Drugs 0.000 description 9
• 229940116977 epidermal growth factor Drugs 0.000 description 9
• 239000012458 free base Substances 0.000 description 9
• 230000012010 growth Effects 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 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 9
• 238000005481 NMR spectroscopy Methods 0.000 description 8
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 8
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 8
• 238000001727 in vivo Methods 0.000 description 8
• 239000003112 inhibitor Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 239000003208 petroleum Substances 0.000 description 8
• 229940002612 prodrug Drugs 0.000 description 8
• 239000000651 prodrug Substances 0.000 description 8
• 101150041968 CDC13 gene Proteins 0.000 description 7
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
• 238000004440 column chromatography Methods 0.000 description 7
• 239000003102 growth factor Substances 0.000 description 7
• 210000004349 growth plate Anatomy 0.000 description 7
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 7
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 7
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 241000699670 Mus sp. Species 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 230000033115 angiogenesis Effects 0.000 description 6
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 6
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 6
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
• KVBQCJXMSFJOFP-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=C(OCC3CCN(C)CC3)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F KVBQCJXMSFJOFP-UHFFFAOYSA-N 0.000 description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 239000012312 sodium hydride Substances 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 150000003840 hydrochlorides Chemical class 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 210000002303 tibia Anatomy 0.000 description 5
• 231100000583 toxicological profile Toxicity 0.000 description 5
• 241000701447 unidentified baculovirus Species 0.000 description 5
• 210000000689 upper leg Anatomy 0.000 description 5
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
• XAVZTXQALXOZJS-UHFFFAOYSA-N 4-chloro-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCC1CCN(C)CC1 XAVZTXQALXOZJS-UHFFFAOYSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 102000001301 EGF receptor Human genes 0.000 description 4
• 108060006698 EGF receptor Proteins 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 206010020880 Hypertrophy Diseases 0.000 description 4
• 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 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 229960001456 adenosine triphosphate Drugs 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 230000009286 beneficial effect Effects 0.000 description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 229960001701 chloroform Drugs 0.000 description 4
• 230000001086 cytosolic effect Effects 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 229910052739 hydrogen Inorganic materials 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
• 230000000306 recurrent effect Effects 0.000 description 4
• 239000000377 silicon dioxide Substances 0.000 description 4
• 238000001228 spectrum Methods 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 206010003210 Arteriosclerosis Diseases 0.000 description 3
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• 229920002785 Croscarmellose sodium Polymers 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 208000007766 Kaposi sarcoma Diseases 0.000 description 3
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
• 235000019759 Maize starch Nutrition 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• 238000000692 Student's t-test Methods 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 108091008605 VEGF receptors Proteins 0.000 description 3
• 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 3
• 229910052783 alkali metal Inorganic materials 0.000 description 3
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
• 229940098773 bovine serum albumin Drugs 0.000 description 3
• 125000001589 carboacyl group Chemical group 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 229960001681 croscarmellose sodium Drugs 0.000 description 3
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 210000002889 endothelial cell Anatomy 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 201000011066 hemangioma Diseases 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 229930182817 methionine Natural products 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 239000001488 sodium phosphate Substances 0.000 description 3
• 229910000162 sodium phosphate Inorganic materials 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 238000012353 t test Methods 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 231100000820 toxicity test Toxicity 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
• 230000004614 tumor growth Effects 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• KWCVUWUJDCWGGM-UHFFFAOYSA-N (6-methoxy-4-oxo-7-phenylmethoxyquinazolin-3-yl)methyl 2,2-dimethylpropanoate Chemical compound COC1=CC(C(N(COC(=O)C(C)(C)C)C=N2)=O)=C2C=C1OCC1=CC=CC=C1 KWCVUWUJDCWGGM-UHFFFAOYSA-N 0.000 description 2
• NZXRRNLMXLRCAF-UHFFFAOYSA-N (7-hydroxy-6-methoxy-4-oxoquinazolin-3-yl)methyl 2,2-dimethylpropanoate Chemical compound N1=CN(COC(=O)C(C)(C)C)C(=O)C2=C1C=C(O)C(OC)=C2 NZXRRNLMXLRCAF-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• BWYJJZBRYSADRP-UHFFFAOYSA-N 2-methoxyquinazoline Chemical compound C1=CC=CC2=NC(OC)=NC=C21 BWYJJZBRYSADRP-UHFFFAOYSA-N 0.000 description 2
• MIUNPJOHLJTRHN-UHFFFAOYSA-N 4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=C(F)C=C(Br)C=C1F MIUNPJOHLJTRHN-UHFFFAOYSA-N 0.000 description 2
• BXQVHAKMPZWSRY-UHFFFAOYSA-N 4-(4-chloro-2,6-difluoroanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=C(F)C=C(Cl)C=C1F BXQVHAKMPZWSRY-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
• BFQSQUAVMNHOEF-UHFFFAOYSA-N 4-bromo-2,6-difluoroaniline Chemical compound NC1=C(F)C=C(Br)C=C1F BFQSQUAVMNHOEF-UHFFFAOYSA-N 0.000 description 2
• GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 2
• AKDPHEYBBWDWCM-UHFFFAOYSA-N 4-chloro-2,6-difluoroaniline Chemical compound NC1=C(F)C=C(Cl)C=C1F AKDPHEYBBWDWCM-UHFFFAOYSA-N 0.000 description 2
• CSFDTBRRIBJILD-UHFFFAOYSA-N 4-chloro-2-fluoroaniline Chemical compound NC1=CC=C(Cl)C=C1F CSFDTBRRIBJILD-UHFFFAOYSA-N 0.000 description 2
• LBGIYCBNJBHZSZ-UHFFFAOYSA-N 4-chloro-6-methoxy-7-phenylmethoxyquinazoline Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCC1=CC=CC=C1 LBGIYCBNJBHZSZ-UHFFFAOYSA-N 0.000 description 2
• NSNFLSUFJFOYIJ-UHFFFAOYSA-N 4-chloro-6-methoxy-7-phenylmethoxyquinazoline;hydrochloride Chemical compound Cl.COC1=CC2=C(Cl)N=CN=C2C=C1OCC1=CC=CC=C1 NSNFLSUFJFOYIJ-UHFFFAOYSA-N 0.000 description 2
• JXVISOHOJNTGTD-UHFFFAOYSA-N 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-1h-quinazolin-4-one Chemical compound COC1=CC(C(NC=N2)=O)=C2C=C1OCC1CCN(C)CC1 JXVISOHOJNTGTD-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 206010051113 Arterial restenosis Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 2
• 201000009273 Endometriosis Diseases 0.000 description 2
• MWAYRGBWOVHDDZ-UHFFFAOYSA-N Ethyl vanillate Chemical compound CCOC(=O)C1=CC=C(O)C(OC)=C1 MWAYRGBWOVHDDZ-UHFFFAOYSA-N 0.000 description 2
• 101150021185 FGF gene Proteins 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 229910021380 Manganese Chloride Inorganic materials 0.000 description 2
• GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 206010027514 Metrorrhagia Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• 208000022873 Ocular disease Diseases 0.000 description 2
• 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108091000080 Phosphotransferase Proteins 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• 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
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 2
• 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 2
• QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 2
• XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 208000038016 acute inflammation Diseases 0.000 description 2
• 230000006022 acute inflammation Effects 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 150000007942 carboxylates Chemical class 0.000 description 2
• 210000000845 cartilage Anatomy 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 230000035194 endochondral ossification Effects 0.000 description 2
• 150000002170 ethers Chemical class 0.000 description 2
• TVBGZCDJLZJQOA-UHFFFAOYSA-N ethyl 2-amino-5-methoxy-4-[(1-methylpiperidin-4-yl)methoxy]benzoate Chemical compound C1=C(N)C(C(=O)OCC)=CC(OC)=C1OCC1CCN(C)CC1 TVBGZCDJLZJQOA-UHFFFAOYSA-N 0.000 description 2
• YKLVXLQPUAUIGF-UHFFFAOYSA-N ethyl 5-methoxy-4-[(1-methylpiperidin-4-yl)methoxy]-2-nitrobenzoate Chemical compound C1=C([N+]([O-])=O)C(C(=O)OCC)=CC(OC)=C1OCC1CCN(C)CC1 YKLVXLQPUAUIGF-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 230000002140 halogenating effect Effects 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
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 210000003559 hypertrophic chondrocyte Anatomy 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 208000017169 kidney disease Diseases 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 239000011565 manganese chloride Substances 0.000 description 2
• 235000002867 manganese chloride Nutrition 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• POJPCDFWVIRKHK-UHFFFAOYSA-N n-(2-fluoro-4-methylphenyl)-6-methoxy-7-phenylmethoxyquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC=C(C)C=C1F POJPCDFWVIRKHK-UHFFFAOYSA-N 0.000 description 2
• MZOZEDJAAFDJOQ-UHFFFAOYSA-N n-(4-bromo-2,6-difluorophenyl)-6-methoxy-7-phenylmethoxyquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=C(F)C=C(Br)C=C1F MZOZEDJAAFDJOQ-UHFFFAOYSA-N 0.000 description 2
• FYZOPODRENDNJN-UHFFFAOYSA-N n-(4-chloro-2,6-difluorophenyl)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3CCNCC3)C(OC)=CC2=C1NC1=C(F)C=C(Cl)C=C1F FYZOPODRENDNJN-UHFFFAOYSA-N 0.000 description 2
• FXDGYJGDFMMIMV-UHFFFAOYSA-N n-(4-chloro-2,6-difluorophenyl)-6-methoxy-7-phenylmethoxyquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=C(F)C=C(Cl)C=C1F FXDGYJGDFMMIMV-UHFFFAOYSA-N 0.000 description 2
• 150000002828 nitro derivatives Chemical class 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
• 239000007981 phosphate-citrate buffer Substances 0.000 description 2
• 102000020233 phosphotransferase Human genes 0.000 description 2
• 229910052697 platinum Inorganic materials 0.000 description 2
• 229920001184 polypeptide Polymers 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 description 2
• 210000001210 retinal vessel Anatomy 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 230000036573 scar formation Effects 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 229960001922 sodium perborate Drugs 0.000 description 2
• YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 230000009790 vascular invasion Effects 0.000 description 2
• WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-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
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
• SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 1
• QVCUKHQDEZNNOC-UHFFFAOYSA-N 1,2-diazabicyclo[2.2.2]octane Chemical compound C1CC2CCN1NC2 QVCUKHQDEZNNOC-UHFFFAOYSA-N 0.000 description 1
• IQFYYKKMVGJFEH-OFKYTIFKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(tritiooxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO[3H])O[C@H]1N1C(=O)NC(=O)C(C)=C1 IQFYYKKMVGJFEH-OFKYTIFKSA-N 0.000 description 1
• 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 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• ZQEXBVHABAJPHJ-UHFFFAOYSA-N 2-fluoro-4-methylaniline Chemical compound CC1=CC=C(N)C(F)=C1 ZQEXBVHABAJPHJ-UHFFFAOYSA-N 0.000 description 1
• AOUFNWPZTOJIFU-UHFFFAOYSA-N 2-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline hydrochloride Chemical compound Cl.COC1=NC2=CC(=CC=C2C=N1)OCC1CCN(CC1)C AOUFNWPZTOJIFU-UHFFFAOYSA-N 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• HQFLTUZKIRYQSP-UHFFFAOYSA-N 3-ethyl-2h-1,3-benzothiazole-6-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2N(CC)CSC2=C1 HQFLTUZKIRYQSP-UHFFFAOYSA-N 0.000 description 1
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
• ZJTCVOGUUPEOGW-UHFFFAOYSA-N 4-(2-fluoro-4-methylanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=C(C)C=C1F ZJTCVOGUUPEOGW-UHFFFAOYSA-N 0.000 description 1
• XIHOMGRMQWNHHB-UHFFFAOYSA-N 4-(4-bromo-2-fluoroanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F XIHOMGRMQWNHHB-UHFFFAOYSA-N 0.000 description 1
• XGZKSSTZBKFZMF-UHFFFAOYSA-N 4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F XGZKSSTZBKFZMF-UHFFFAOYSA-N 0.000 description 1
• QZFWATQEEPAGAF-UHFFFAOYSA-N 4-chloro-2,6-difluoroaniline;hydrochloride Chemical compound Cl.NC1=C(F)C=C(Cl)C=C1F QZFWATQEEPAGAF-UHFFFAOYSA-N 0.000 description 1
• SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 1
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
• LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• ZCUFFSHMOAEEIL-UHFFFAOYSA-N 6-methoxy-7-phenylmethoxy-1h-quinazolin-4-one Chemical compound COC1=CC2=C(O)N=CN=C2C=C1OCC1=CC=CC=C1 ZCUFFSHMOAEEIL-UHFFFAOYSA-N 0.000 description 1
• VFSJPKSXNJQIFG-UHFFFAOYSA-N 6-methoxyquinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC(OC)=CC=C21 VFSJPKSXNJQIFG-UHFFFAOYSA-N 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 102000012936 Angiostatins Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
• 102000015790 Asparaginase Human genes 0.000 description 1
• 108010024976 Asparaginase Proteins 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• VRXVUCLJIJWDMH-UHFFFAOYSA-N Cl.C1=CC=CC2=NC(OC)=NC=C21 Chemical compound Cl.C1=CC=CC2=NC(OC)=NC=C21 VRXVUCLJIJWDMH-UHFFFAOYSA-N 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
• 102400001047 Endostatin Human genes 0.000 description 1
• 108010079505 Endostatins Proteins 0.000 description 1
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
• 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
• 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
• 108010069236 Goserelin Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
• 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
• 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
• 239000005909 Kieselgur Substances 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
• 206010027476 Metastases Diseases 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 241000256251 Spodoptera frugiperda Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 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
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
• 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 108020005202 Viral DNA Proteins 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• UDQOUIKKIADMCY-UHFFFAOYSA-N [6-methoxy-4-oxo-7-(piperidin-4-ylmethoxy)quinazolin-3-yl]methyl 2,2-dimethylpropanoate Chemical compound COC1=CC(C(N(COC(=O)C(C)(C)C)C=N2)=O)=C2C=C1OCC1CCNCC1 UDQOUIKKIADMCY-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 108010023617 abarelix Proteins 0.000 description 1
• 229960002184 abarelix Drugs 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 150000003838 adenosines Chemical class 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
• 150000008046 alkali metal hydrides Chemical class 0.000 description 1
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 150000001413 amino acids Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229960001220 amsacrine Drugs 0.000 description 1
• XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
• 229960002932 anastrozole Drugs 0.000 description 1
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 230000003432 anti-folate effect Effects 0.000 description 1
• 230000001740 anti-invasion Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000002927 anti-mitotic effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940127074 antifolate Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
• 229960003272 asparaginase Drugs 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 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
• 239000012298 atmosphere Substances 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• 238000000498 ball milling Methods 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 229960002092 busulfan Drugs 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
• 230000003185 calcium uptake Effects 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical group [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 125000001721 carboxyacetyl group Chemical group 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
• 229940046044 combinations of antineoplastic agent Drugs 0.000 description 1
• LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229960000978 cyproterone acetate Drugs 0.000 description 1
• UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
• 239000002274 desiccant Substances 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 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
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
• 239000012153 distilled water Substances 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
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 229950004203 droloxifene Drugs 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 229960001776 edrecolomab Drugs 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• LRHBZJAIQBBNFI-UHFFFAOYSA-N ethyl 3-methoxy-4-[(1-methylpiperidin-4-yl)methoxy]benzoate Chemical compound COC1=CC(C(=O)OCC)=CC=C1OCC1CCN(C)CC1 LRHBZJAIQBBNFI-UHFFFAOYSA-N 0.000 description 1
• RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 229960000255 exemestane Drugs 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 210000000521 femorotibial joint Anatomy 0.000 description 1
• DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
• 229960004039 finasteride Drugs 0.000 description 1
• 150000005699 fluoropyrimidines Chemical class 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
• 229960002074 flutamide Drugs 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
• 229960003690 goserelin acetate Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000009036 growth inhibition Effects 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 229960000890 hydrocortisone Drugs 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• 229960001101 ifosfamide Drugs 0.000 description 1
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
• 238000010191 image analysis Methods 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 150000002485 inorganic esters Chemical class 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 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 1
• 229960004768 irinotecan Drugs 0.000 description 1
• 150000002505 iron Chemical class 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 229960003881 letrozole Drugs 0.000 description 1
• 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 1
• 239000003446 ligand Substances 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 239000008263 liquid aerosol Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 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
• OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
• 229950008959 marimastat Drugs 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 108010082117 matrigel Proteins 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960004296 megestrol acetate Drugs 0.000 description 1
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 230000003562 morphometric effect Effects 0.000 description 1
• 238000013425 morphometry Methods 0.000 description 1
• IMCCZKHIPVEUEI-UHFFFAOYSA-N n,n-difluoroaniline Chemical compound FN(F)C1=CC=CC=C1 IMCCZKHIPVEUEI-UHFFFAOYSA-N 0.000 description 1
• FZMIEQCEGTVFBZ-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CN=C2C=C(OCC3CCN(C)CC3)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F FZMIEQCEGTVFBZ-UHFFFAOYSA-N 0.000 description 1
• CAJIOLKERBQYCQ-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-6-methoxy-7-phenylmethoxyquinazolin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F CAJIOLKERBQYCQ-UHFFFAOYSA-N 0.000 description 1
• JOHNIYZRJXDVBV-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-phenylmethoxyquinazolin-4-amine;hydrochloride Chemical compound Cl.N1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F JOHNIYZRJXDVBV-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
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
• KLOQOWQKKZSVJD-UHFFFAOYSA-N n-fluoro-4-methylaniline Chemical compound CC1=CC=C(NF)C=C1 KLOQOWQKKZSVJD-UHFFFAOYSA-N 0.000 description 1
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
• 230000017066 negative regulation of growth Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
• 229960002653 nilutamide Drugs 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000003305 oral gavage Methods 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000011164 ossification Effects 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000001575 pathological effect Effects 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
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000003014 phosphoric acid esters Chemical class 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 150000003057 platinum Chemical class 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 239000000583 progesterone congener Substances 0.000 description 1
• 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
• 229960004432 raltitrexed Drugs 0.000 description 1
• 229920005604 random copolymer Polymers 0.000 description 1
• 229960000460 razoxane Drugs 0.000 description 1
• BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000000630 rising effect Effects 0.000 description 1
• 229960003522 roquinimex Drugs 0.000 description 1
• 238000002390 rotary evaporation Methods 0.000 description 1
• 108091008601 sVEGFR Proteins 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000004017 serum-free culture medium Substances 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
• 239000001117 sulphuric acid Substances 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 238000003419 tautomerization reaction Methods 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
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• CTEDVGRUGMPBHE-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CO)CC1 CTEDVGRUGMPBHE-UHFFFAOYSA-N 0.000 description 1
• DJQLEEANCWENKG-UHFFFAOYSA-N tert-butyl 4-[[4-(4-bromo-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidine-1-carboxylate Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)OC(C)(C)C)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F DJQLEEANCWENKG-UHFFFAOYSA-N 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229960003433 thalidomide Drugs 0.000 description 1
• 229960001196 thiotepa Drugs 0.000 description 1
• 239000003734 thymidylate synthase inhibitor 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
• 238000011200 topical administration Methods 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
• 229960005026 toremifene Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 210000003606 umbilical vein Anatomy 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 230000006711 vascular endothelial growth factor production Effects 0.000 description 1
• 239000013598 vector Substances 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 210000003905 vulva Anatomy 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1