KR20060058781A

KR20060058781A - Ｖｅｇｆ 수용체 티로신 키나아제의 억제제로서의 퀴나졸린유도체

Ｖｅｇｆ 수용체 티로신 키나아제의 억제제로서의 퀴나졸린유도체 Download PDF

Info

Publication number: KR20060058781A
Authority: KR; South Korea
Prior art keywords: alkyl; alkanoyl; alkylaminoc; aminoc; defined above
Prior art date: 2003-08-06
Legal status : Withdrawn

Application number

KR1020067002552A

Other languages

English (en)

Korean (ko)

Inventor

로랑 프랑수아 앙드레 앙느깽

Original Assignee

아스트라제네카 아베

Priority date

2003-08-06

Filing date

2004-08-05

Publication date

2006-05-30

2004-08-05 Application filed by 아스트라제네카 아베 filed Critical 아스트라제네카 아베

2006-05-30 Publication of KR20060058781A publication Critical patent/KR20060058781A/ko

Status Withdrawn legal-status Critical Current

Links

108091008598 receptor tyrosine kinases Proteins 0.000 title description 14
102000027426 receptor tyrosine kinases Human genes 0.000 title description 14
239000003112 inhibitor Substances 0.000 title description 12
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical class N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 title description 5
125000000217 alkyl group Chemical group 0.000 claims abstract description 975
150000001875 compounds Chemical class 0.000 claims abstract description 196
125000003545 alkoxy group Chemical group 0.000 claims abstract description 166
150000003839 salts Chemical class 0.000 claims abstract description 81
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 64
239000001257 hydrogen Substances 0.000 claims abstract description 64
238000000034 method Methods 0.000 claims abstract description 41
241001465754 Metazoa Species 0.000 claims abstract description 18
230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 12
239000003814 drug Substances 0.000 claims abstract description 12
238000004519 manufacturing process Methods 0.000 claims abstract description 9
230000001603 reducing effect Effects 0.000 claims abstract description 9
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 6
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
125000001589 carboacyl group Chemical group 0.000 claims description 346
125000000623 heterocyclic group Chemical group 0.000 claims description 205
125000001424 substituent group Chemical group 0.000 claims description 194
-1 methylenedioxy Chemical group 0.000 claims description 168
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 120
229910052757 nitrogen Inorganic materials 0.000 claims description 104
125000000304 alkynyl group Chemical group 0.000 claims description 98
125000003342 alkenyl group Chemical group 0.000 claims description 96
229920006395 saturated elastomer Polymers 0.000 claims description 87
125000005842 heteroatom Chemical group 0.000 claims description 77
229910052760 oxygen Inorganic materials 0.000 claims description 69
229910052717 sulfur Inorganic materials 0.000 claims description 68
125000005843 halogen group Chemical group 0.000 claims description 67
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 60
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 59
150000002431 hydrogen Chemical class 0.000 claims description 55
125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 50
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 50
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
125000004043 oxo group Chemical group O=* 0.000 claims description 45
125000003282 alkyl amino group Chemical group 0.000 claims description 44
125000004093 cyano group Chemical group *C#N 0.000 claims description 43
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 41
125000004103 aminoalkyl group Chemical group 0.000 claims description 38
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 36
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 36
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 35
125000004966 cyanoalkyl group Chemical group 0.000 claims description 33
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 32
125000004122 cyclic group Chemical group 0.000 claims description 28
125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 18
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 17
230000002792 vascular Effects 0.000 claims description 16
125000001153 fluoro group Chemical group F* 0.000 claims description 15
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 14
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 12
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
241001648652 Croton ovalifolius Species 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
WLAGZIBGTRJBLJ-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-(2-methoxyethylamino)ethanone Chemical compound C1CN(C(=O)CNCCOC)CCC1COC1=CC2=NC=NC(NC=3C(=CC(Cl)=CC=3)F)=C2C=C1OC WLAGZIBGTRJBLJ-UHFFFAOYSA-N 0.000 claims description 3
HFWPMRCXAOALMT-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-(3,3-difluoropyrrolidin-1-yl)ethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN3CC(F)(F)CC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F HFWPMRCXAOALMT-UHFFFAOYSA-N 0.000 claims description 3
FAANUEQUJPCZNF-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-(methylamino)ethanone Chemical compound C1CN(C(=O)CNC)CCC1COC1=CC2=NC=NC(NC=3C(=CC(Cl)=CC=3)F)=C2C=C1OC FAANUEQUJPCZNF-UHFFFAOYSA-N 0.000 claims description 3
SEILYBVXQXQCKV-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-morpholin-4-ylethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN3CCOCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F SEILYBVXQXQCKV-UHFFFAOYSA-N 0.000 claims description 3
PZGRIHOWUZQLNY-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN3CCCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F PZGRIHOWUZQLNY-UHFFFAOYSA-N 0.000 claims description 3
ZLGXMJUMDIQCQX-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)-1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]ethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN3CCN(CC3)C(C)=O)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F ZLGXMJUMDIQCQX-UHFFFAOYSA-N 0.000 claims description 3
206010041349 Somnolence Diseases 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
JGLLVNSIUQPNQA-MRXNPFEDSA-N 1-[(3r)-3-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound N1=CN=C2C=C(OC[C@H]3CN(CCC3)C(=O)CN(C)C)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F JGLLVNSIUQPNQA-MRXNPFEDSA-N 0.000 claims description 2
JGLLVNSIUQPNQA-INIZCTEOSA-N 1-[(3s)-3-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound N1=CN=C2C=C(OC[C@@H]3CN(CCC3)C(=O)CN(C)C)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F JGLLVNSIUQPNQA-INIZCTEOSA-N 0.000 claims description 2
IWASYXNYJUYQBV-UHFFFAOYSA-N 1-[4-[2-[4-(4-bromo-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxyethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound N1=CN=C2C=C(OCCC3CCN(CC3)C(=O)CN(C)C)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F IWASYXNYJUYQBV-UHFFFAOYSA-N 0.000 claims description 2
VYRBUOLLDDZYRU-UHFFFAOYSA-N 1-[4-[2-[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxyethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound N1=CN=C2C=C(OCCC3CCN(CC3)C(=O)CN(C)C)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F VYRBUOLLDDZYRU-UHFFFAOYSA-N 0.000 claims description 2
ILOFHIKOHSYOMT-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN(C)C)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F ILOFHIKOHSYOMT-UHFFFAOYSA-N 0.000 claims description 2
OCYPSDDYPPRKEV-UHFFFAOYSA-N 1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-piperidin-1-ylethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN3CCCCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F OCYPSDDYPPRKEV-UHFFFAOYSA-N 0.000 claims description 2
IKUGFRROILOMDR-WMPKNSHKSA-N 2-[(3ar,6as)-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl]-1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]ethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CN3C[C@@H]4OCO[C@@H]4C3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F IKUGFRROILOMDR-WMPKNSHKSA-N 0.000 claims description 2
RTDCVKKDDKPPHK-OYRHEFFESA-N 7-[2-[(3as,6ar)-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl]ethoxy]-n-(4-bromo-2-fluorophenyl)-6-methoxyquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCN3C[C@@H]4OCO[C@@H]4C3)C(OC)=CC2=C1NC1=CC=C(Br)C=C1F RTDCVKKDDKPPHK-OYRHEFFESA-N 0.000 claims description 2
RVTANFFPLYGDFU-SZPZYZBQSA-N 7-[3-[(3aS,6aR)-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrol-5-yl]propoxy]-N-(4-bromo-2-fluorophenyl)-6-methoxyquinazolin-2-amine Chemical compound N1=C2C=C(OCCCN3C[C@@H]4OCO[C@@H]4C3)C(OC)=CC2=CN=C1NC1=CC=C(Br)C=C1F RVTANFFPLYGDFU-SZPZYZBQSA-N 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
KRZJRNZICWNMOA-GXSJLCMTSA-N (3s,4r)-4,8-dihydroxy-3-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2[C@@H](O)[C@@H](OC)CC(=O)C2=C1O KRZJRNZICWNMOA-GXSJLCMTSA-N 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 29
206010028980 Neoplasm Diseases 0.000 abstract description 22
238000011282 treatment Methods 0.000 abstract description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
201000010099 disease Diseases 0.000 abstract description 12
230000033115 angiogenesis Effects 0.000 abstract description 10
201000011510 cancer Diseases 0.000 abstract description 9
238000002360 preparation method Methods 0.000 abstract description 6
230000002137 anti-vascular effect Effects 0.000 abstract description 4
206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 2
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
125000004356 hydroxy functional group Chemical group O* 0.000 description 46
239000000203 mixture Substances 0.000 description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
238000001228 spectrum Methods 0.000 description 35
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
239000007787 solid Substances 0.000 description 32
239000000243 solution Substances 0.000 description 32
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 30
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 29
238000006243 chemical reaction Methods 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
239000011541 reaction mixture Substances 0.000 description 23
239000007858 starting material Substances 0.000 description 23
210000004027 cell Anatomy 0.000 description 22
238000012360 testing method Methods 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
238000004440 column chromatography Methods 0.000 description 19
230000008569 process Effects 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
229910021529 ammonia Inorganic materials 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
230000002829 reductive effect Effects 0.000 description 15
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 14
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
238000003556 assay Methods 0.000 description 12
238000010992 reflux Methods 0.000 description 12
239000002904 solvent Substances 0.000 description 12
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 12
102400001368 Epidermal growth factor Human genes 0.000 description 11
101800003838 Epidermal growth factor Proteins 0.000 description 11
239000002585 base Substances 0.000 description 11
229940116977 epidermal growth factor Drugs 0.000 description 11
239000003102 growth factor Substances 0.000 description 11
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
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
102000004190 Enzymes Human genes 0.000 description 10
108090000790 Enzymes Proteins 0.000 description 10
FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 10
239000012267 brine Substances 0.000 description 10
239000003701 inert diluent Substances 0.000 description 10
229940002612 prodrug Drugs 0.000 description 10
239000000651 prodrug Substances 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 9
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
229940088598 enzyme Drugs 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
238000013459 approach Methods 0.000 description 8
238000001914 filtration Methods 0.000 description 8
238000001727 in vivo Methods 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
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
102000005962 receptors Human genes 0.000 description 8
108020003175 receptors Proteins 0.000 description 8
238000007363 ring formation reaction Methods 0.000 description 8
239000003826 tablet Substances 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
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 8
241000282412 Homo Species 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
239000003795 chemical substances by application Substances 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
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 6
150000001721 carbon Chemical group 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
239000002552 dosage form Substances 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
230000012010 growth Effects 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
BXRGTEOKLSVMJU-UHFFFAOYSA-N 4-chloro-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1Cl BXRGTEOKLSVMJU-UHFFFAOYSA-N 0.000 description 5
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 5
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 5
108091003079 Bovine Serum Albumin Proteins 0.000 description 5
0 Cc1cc2ncnc(*c(ccc(*)c3)c3F)c2cc1* Chemical compound Cc1cc2ncnc(*c(ccc(*)c3)c3F)c2cc1* 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
229960001456 adenosine triphosphate Drugs 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
108700003601 dimethylglycine Proteins 0.000 description 5
210000002889 endothelial cell Anatomy 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229940078490 n,n-dimethylglycine Drugs 0.000 description 5
239000002953 phosphate buffered saline Substances 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
230000009467 reduction Effects 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
CSFDTBRRIBJILD-UHFFFAOYSA-N 4-chloro-2-fluoroaniline Chemical compound NC1=CC=C(Cl)C=C1F CSFDTBRRIBJILD-UHFFFAOYSA-N 0.000 description 4
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 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
239000005541 ACE inhibitor Substances 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
208000001953 Hypotension Diseases 0.000 description 4
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 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
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
229910052784 alkaline earth metal Inorganic materials 0.000 description 4
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 4
239000002220 antihypertensive agent Substances 0.000 description 4
210000003050 axon Anatomy 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
239000002775 capsule Substances 0.000 description 4
150000007942 carboxylates Chemical class 0.000 description 4
229960001701 chloroform Drugs 0.000 description 4
230000001086 cytosolic effect Effects 0.000 description 4
238000001514 detection method Methods 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
208000021822 hypotensive Diseases 0.000 description 4
230000001077 hypotensive effect Effects 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 4
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 4
230000000306 recurrent effect Effects 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
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 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
241000701447 unidentified baculovirus Species 0.000 description 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
201000001320 Atherosclerosis Diseases 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 3
229940127291 Calcium channel antagonist Drugs 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
229920002785 Croscarmellose sodium Polymers 0.000 description 3
102000001301 EGF receptor Human genes 0.000 description 3
108060006698 EGF receptor Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-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
241000699666 Mus <mouse, genus> Species 0.000 description 3
101100372761 Mus musculus Flt1 gene Proteins 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
208000034038 Pathologic Neovascularization Diseases 0.000 description 3
102000004257 Potassium Channel Human genes 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
101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
235000011114 ammonium hydroxide Nutrition 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
229940030600 antihypertensive agent Drugs 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
230000036772 blood pressure Effects 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
239000000480 calcium channel blocker Substances 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
230000004663 cell proliferation Effects 0.000 description 3
238000002512 chemotherapy Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
229960001681 croscarmellose sodium Drugs 0.000 description 3
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
239000012045 crude solution Substances 0.000 description 3
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
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 3
150000002170 ethers Chemical class 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
230000006870 function Effects 0.000 description 3
BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 3
201000011066 hemangioma Diseases 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
230000001939 inductive effect Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
229930182817 methionine Natural products 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
108020001213 potassium channel Proteins 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
125000000719 pyrrolidinyl group Chemical group 0.000 description 3
150000003246 quinazolines Chemical class 0.000 description 3
210000003491 skin Anatomy 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000001488 sodium phosphate Substances 0.000 description 3
229910000162 sodium phosphate Inorganic materials 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000011550 stock solution Substances 0.000 description 3
239000000758 substrate Substances 0.000 description 3
210000001519 tissue Anatomy 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
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
230000008728 vascular permeability Effects 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
ZTOJFFHGPLIVKC-YAFCTCPESA-N (2e)-3-ethyl-2-[(z)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S\1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C/1=N/N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-YAFCTCPESA-N 0.000 description 2
UVNGEPOWQCFTDI-UHFFFAOYSA-N (6-methoxy-4-oxo-1h-quinazolin-7-yl) acetate Chemical compound N1=CNC(=O)C2=C1C=C(OC(C)=O)C(OC)=C2 UVNGEPOWQCFTDI-UHFFFAOYSA-N 0.000 description 2
DNPHXICYCDCOAR-UHFFFAOYSA-N 2-amino-5-methoxy-4-phenylmethoxybenzamide Chemical compound COC1=CC(C(N)=O)=C(N)C=C1OCC1=CC=CC=C1 DNPHXICYCDCOAR-UHFFFAOYSA-N 0.000 description 2
YJGACXPWXDBICM-UHFFFAOYSA-N 2-chloro-1-[4-[[4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]ethanone Chemical compound N1=CN=C2C=C(OCC3CCN(CC3)C(=O)CCl)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F YJGACXPWXDBICM-UHFFFAOYSA-N 0.000 description 2
MDBOZMACAZGNHS-UHFFFAOYSA-N 4,5,6,6a-tetrahydro-3ah-[1,3]dioxolo[4,5-c]pyrrole Chemical compound C1NCC2OCOC21 MDBOZMACAZGNHS-UHFFFAOYSA-N 0.000 description 2
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 2
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 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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
ZHLRYPLSYOYNQM-UHFFFAOYSA-N 7-hydroxy-6-methoxy-1h-quinazolin-4-one Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1O ZHLRYPLSYOYNQM-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
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
108020004414 DNA Proteins 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical class CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 2
201000009273 Endometriosis Diseases 0.000 description 2
108010041308 Endothelial Growth Factors Proteins 0.000 description 2
108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 2
102100031706 Fibroblast growth factor 1 Human genes 0.000 description 2
241000238631 Hexapoda 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
239000005909 Kieselgur Substances 0.000 description 2
206010025282 Lymphoedema Diseases 0.000 description 2
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical class NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
206010027514 Metrorrhagia Diseases 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
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
229910021607 Silver chloride Inorganic materials 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 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
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-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
206010052428 Wound Diseases 0.000 description 2
208000027418 Wounds and injury Diseases 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
230000003213 activating effect Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
208000038016 acute inflammation Diseases 0.000 description 2
230000006022 acute inflammation Effects 0.000 description 2
239000000556 agonist Substances 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000004037 angiogenesis inhibitor Substances 0.000 description 2
239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
230000000692 anti-sense effect Effects 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
238000000149 argon plasma sintering Methods 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
102000012740 beta Adrenergic Receptors Human genes 0.000 description 2
108010079452 beta Adrenergic Receptors Proteins 0.000 description 2
239000002876 beta blocker Substances 0.000 description 2
229940097320 beta blocking agent Drugs 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 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
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
229960001433 erlotinib Drugs 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000006260 foam Substances 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
239000012634 fragment Substances 0.000 description 2
239000012458 free base Substances 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
239000000499 gel Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
229910052737 gold Inorganic materials 0.000 description 2
239000010931 gold 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
238000010348 incorporation Methods 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
208000017169 kidney disease Diseases 0.000 description 2
210000002429 large intestine Anatomy 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
208000002502 lymphedema Diseases 0.000 description 2
229910001629 magnesium chloride Inorganic materials 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
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
238000013508 migration Methods 0.000 description 2
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 2
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 2
150000002828 nitro derivatives Chemical class 0.000 description 2
208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase 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
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
229940068918 polyethylene glycol 400 Drugs 0.000 description 2
229920001184 polypeptide Polymers 0.000 description 2
239000001103 potassium chloride Substances 0.000 description 2
235000011164 potassium chloride Nutrition 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
238000000746 purification Methods 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
238000001959 radiotherapy Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
230000002207 retinal effect Effects 0.000 description 2
238000012552 review Methods 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
229910052709 silver Inorganic materials 0.000 description 2
239000004332 silver Substances 0.000 description 2
HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 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
238000010561 standard procedure Methods 0.000 description 2
230000004936 stimulating effect Effects 0.000 description 2
MAXQBMZDVBHSLW-UHFFFAOYSA-N tert-butyl 3,4-dihydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(O)C(O)C1 MAXQBMZDVBHSLW-UHFFFAOYSA-N 0.000 description 2
HFUHSIILHDVFPQ-UHFFFAOYSA-N tert-butyl 3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate Chemical compound O1COC2CN(C(=O)OC(C)(C)C)CC21 HFUHSIILHDVFPQ-UHFFFAOYSA-N 0.000 description 2
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 2
DLDGRYDIAFYLSH-UHFFFAOYSA-N tert-butyl 4-[(4-chloro-6-methoxyquinazolin-7-yl)oxymethyl]piperidine-1-carboxylate Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCC1CCN(C(=O)OC(C)(C)C)CC1 DLDGRYDIAFYLSH-UHFFFAOYSA-N 0.000 description 2
NEDQLWFPVBNZSR-UHFFFAOYSA-N tert-butyl 4-[2-(4-chloro-6-methoxyquinazolin-7-yl)oxyethyl]piperidine-1-carboxylate Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCCC1CCN(C(=O)OC(C)(C)C)CC1 NEDQLWFPVBNZSR-UHFFFAOYSA-N 0.000 description 2
RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 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
238000004809 thin layer chromatography Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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 class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
239000004066 vascular targeting agent Substances 0.000 description 2
ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-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
GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
TUKVTPQCBBQLHP-UHFFFAOYSA-N 2-(piperidin-4-ylmethoxy)quinazoline Chemical compound N=1C=C2C=CC=CC2=NC=1OCC1CCNCC1 TUKVTPQCBBQLHP-UHFFFAOYSA-N 0.000 description 1
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-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
BWYJJZBRYSADRP-UHFFFAOYSA-N 2-methoxyquinazoline Chemical compound C1=CC=CC2=NC(OC)=NC=C21 BWYJJZBRYSADRP-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
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
ZTOJFFHGPLIVKC-UHFFFAOYSA-N 3-ethyl-2-[(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C1=NN=C1SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-UHFFFAOYSA-N 0.000 description 1
JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-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
VRDGPSDTYIITKT-UHFFFAOYSA-N 4,5,6,6a-tetrahydro-3ah-[1,3]dioxolo[4,5-c]pyrrole;hydrochloride Chemical compound Cl.O1COC2CNCC21 VRDGPSDTYIITKT-UHFFFAOYSA-N 0.000 description 1
JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-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
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
229920001817 Agar Polymers 0.000 description 1
102400000068 Angiostatin Human genes 0.000 description 1
108010079709 Angiostatins Proteins 0.000 description 1
241000156724 Antirhea Species 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
108090000461 Aurora Kinase A Proteins 0.000 description 1
102100032311 Aurora kinase A Human genes 0.000 description 1
108700020463 BRCA1 Proteins 0.000 description 1
102000036365 BRCA1 Human genes 0.000 description 1
101150072950 BRCA1 gene Proteins 0.000 description 1
102000052609 BRCA2 Human genes 0.000 description 1
108700020462 BRCA2 Proteins 0.000 description 1
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
101150008921 Brca2 gene 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
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
108091006146 Channels Proteins 0.000 description 1
235000001258 Cinchona calisaya Nutrition 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
102000000311 Cytosine Deaminase Human genes 0.000 description 1
108010080611 Cytosine Deaminase Proteins 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
206010012689 Diabetic retinopathy Diseases 0.000 description 1
239000006145 Eagle's minimal essential medium Substances 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
101150009958 FLT4 gene Proteins 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
101150048336 Flt1 gene Proteins 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
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 1
101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
108010069236 Goserelin Proteins 0.000 description 1
239000007995 HEPES buffer Substances 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
101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-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
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
JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
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
108010047852 Integrin alphaVbeta3 Proteins 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000000588 Interleukin-2 Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
102000004388 Interleukin-4 Human genes 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
241000764238 Isis Species 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
239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
108010000817 Leuprolide Proteins 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
108700041567 MDR Genes Proteins 0.000 description 1
102000010750 Metalloproteins Human genes 0.000 description 1
108010063312 Metalloproteins Proteins 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
241001024304 Mino Species 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
206010028289 Muscle atrophy Diseases 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-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
LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
102000004459 Nitroreductase Human genes 0.000 description 1
208000022873 Ocular disease Diseases 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
235000019502 Orange oil Nutrition 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
108091005804 Peptidases Proteins 0.000 description 1
229920005439 Perspex® Polymers 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
206010035226 Plasma cell myeloma Diseases 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
239000004365 Protease Substances 0.000 description 1
229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 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
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
241000256251 Spodoptera frugiperda Species 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
102000006601 Thymidine Kinase Human genes 0.000 description 1
108020004440 Thymidine kinase Proteins 0.000 description 1
IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
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
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
229940122803 Vinca alkaloid Drugs 0.000 description 1
108020005202 Viral DNA Proteins 0.000 description 1
241000700605 Viruses Species 0.000 description 1
108010076089 accutase Proteins 0.000 description 1
150000001242 acetic acid derivatives Chemical class 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
230000004913 activation Effects 0.000 description 1
150000003838 adenosines Chemical class 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
238000012382 advanced drug delivery Methods 0.000 description 1
239000008272 agar Substances 0.000 description 1
230000032683 aging Effects 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides 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
208000026935 allergic disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
125000002820 allylidene group Chemical group [H]C(=[*])C([H])=C([H])[H] 0.000 description 1
102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
239000002160 alpha blocker Substances 0.000 description 1
229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
DOAYJPJLHNHQSU-UHFFFAOYSA-N aluminum;lithium;hydrate Chemical compound [Li].O.[Al] DOAYJPJLHNHQSU-UHFFFAOYSA-N 0.000 description 1
150000001413 amino acids Chemical group 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical class 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
229960001220 amsacrine Drugs 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
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
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
230000003527 anti-angiogenesis Effects 0.000 description 1
230000003432 anti-folate effect Effects 0.000 description 1
230000000340 anti-metabolite 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
239000003080 antimitotic agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 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
229940120638 avastin Drugs 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical class N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
229960000397 bevacizumab Drugs 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000005388 borosilicate glass Substances 0.000 description 1
SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 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
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
230000003185 calcium uptake Effects 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
229940127093 camptothecin Drugs 0.000 description 1
229950002826 canertinib Drugs 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 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
150000001735 carboxylic acids Chemical class 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
230000012292 cell migration Effects 0.000 description 1
238000001516 cell proliferation assay Methods 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
229940081734 cellulose acetate phthalate Drugs 0.000 description 1
229960005395 cetuximab Drugs 0.000 description 1
230000008859 change Effects 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000003638 chemical reducing agent Substances 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
229960004630 chlorambucil Drugs 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 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
229940047120 colony stimulating factors Drugs 0.000 description 1
238000011284 combination treatment Methods 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
238000001816 cooling Methods 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
238000012136 culture method Methods 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
229960003843 cyproterone 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
229940127089 cytotoxic agent Drugs 0.000 description 1
229960000640 dactinomycin Drugs 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
210000004443 dendritic cell Anatomy 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
FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
235000015872 dietary supplement Nutrition 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
239000006185 dispersion Substances 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
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
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
230000007831 electrophysiology Effects 0.000 description 1
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000001952 enzyme assay Methods 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
230000008472 epithelial growth Effects 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
102000015694 estrogen receptors Human genes 0.000 description 1
108010038795 estrogen receptors Proteins 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
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
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
208000030533 eye disease Diseases 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
229960004039 finasteride Drugs 0.000 description 1
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
229960002258 fulvestrant Drugs 0.000 description 1
229960002584 gefitinib Drugs 0.000 description 1
238000001415 gene therapy Methods 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
239000001963 growth medium Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
229940022353 herceptin Drugs 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
239000005457 ice water Substances 0.000 description 1
229960000908 idarubicin Drugs 0.000 description 1
HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
229960001101 ifosfamide Drugs 0.000 description 1
238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
230000001024 immunotherapeutic effect Effects 0.000 description 1
238000009169 immunotherapy Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
150000002485 inorganic esters Chemical class 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
238000012739 integrated shape imaging system Methods 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
229940028885 interleukin-4 Drugs 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
229960004768 irinotecan Drugs 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
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
210000003734 kidney Anatomy 0.000 description 1
229940043355 kinase inhibitor Drugs 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
229960004338 leuprorelin Drugs 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
239000007937 lozenge Substances 0.000 description 1
208000002780 macular degeneration Diseases 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
HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
229960004961 mechlorethamine Drugs 0.000 description 1
239000002609 medium Substances 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
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
229960001924 melphalan Drugs 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 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
230000005012 migration Effects 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
239000003607 modifier Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
WHYJHPLPIYHJTH-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=CC=C12 WHYJHPLPIYHJTH-UHFFFAOYSA-N 0.000 description 1
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 description 1
VFEJMQCGWYJTJQ-CYBMUJFWSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-[[(3r)-piperidin-3-yl]methoxy]quinazolin-4-amine Chemical compound N1=CN=C2C=C(OC[C@H]3CNCCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F VFEJMQCGWYJTJQ-CYBMUJFWSA-N 0.000 description 1
VFEJMQCGWYJTJQ-ZDUSSCGKSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-[[(3s)-piperidin-3-yl]methoxy]quinazolin-4-amine Chemical compound N1=CN=C2C=C(OC[C@@H]3CNCCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F VFEJMQCGWYJTJQ-ZDUSSCGKSA-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
AHLKSOXEVRYIRD-UHFFFAOYSA-N n-phenylquinazolin-2-amine Chemical class N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=C1 AHLKSOXEVRYIRD-UHFFFAOYSA-N 0.000 description 1
230000018791 negative regulation of catalytic activity Effects 0.000 description 1
230000017066 negative regulation of growth Effects 0.000 description 1
108020001162 nitroreductase Proteins 0.000 description 1
OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
230000008520 organization Effects 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000012402 patch clamp technique Methods 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000009120 phenotypic response Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
102000020233 phosphotransferase Human genes 0.000 description 1
239000003757 phosphotransferase inhibitor Substances 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
150000003057 platinum Chemical class 0.000 description 1
229960003171 plicamycin Drugs 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
239000003450 potassium channel blocker Substances 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 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
VIXWGKYSYIBATJ-UHFFFAOYSA-N pyrrol-2-one Chemical compound O=C1C=CC=N1 VIXWGKYSYIBATJ-UHFFFAOYSA-N 0.000 description 1
229960000948 quinine Drugs 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
230000001850 reproductive effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
238000005070 sampling Methods 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
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 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
238000010532 solid phase synthesis reaction Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000012258 stirred mixture Substances 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
150000003460 sulfonic acids Chemical class 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
230000004083 survival effect Effects 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
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
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
OJCLHERKFHHUTB-SECBINFHSA-N tert-butyl (3r)-3-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H](CO)C1 OJCLHERKFHHUTB-SECBINFHSA-N 0.000 description 1
CLCDLCFSOLUQNN-CYBMUJFWSA-N tert-butyl (3r)-3-[(4-chloro-6-methoxyquinazolin-7-yl)oxymethyl]piperidine-1-carboxylate Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OC[C@@H]1CCCN(C(=O)OC(C)(C)C)C1 CLCDLCFSOLUQNN-CYBMUJFWSA-N 0.000 description 1
YEBDZDMYLQHGGZ-UHFFFAOYSA-N tert-butyl 2,5-dihydropyrrole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC1 YEBDZDMYLQHGGZ-UHFFFAOYSA-N 0.000 description 1
YBNJZIDYXCGAPX-UHFFFAOYSA-N tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CCO)CC1 YBNJZIDYXCGAPX-UHFFFAOYSA-N 0.000 description 1
LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-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
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
238000002560 therapeutic procedure Methods 0.000 description 1
229960001196 thiotepa Drugs 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
239000003734 thymidylate synthase inhibitor Substances 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
239000003558 transferase inhibitor Substances 0.000 description 1
230000007704 transition Effects 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
229960000575 trastuzumab Drugs 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
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
210000004881 tumor cell Anatomy 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
230000006426 vascular sprouting Effects 0.000 description 1
230000004862 vasculogenesis Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 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
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
229960004355 vindesine Drugs 0.000 description 1
UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
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
210000003905 vulva Anatomy 0.000 description 1
238000005406 washing Methods 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