ES2253786T3 - Compuestos de ciclopropilindola y su uso como precursores de medicamentos. - Google Patents
Compuestos de ciclopropilindola y su uso como precursores de medicamentos.Info
- Publication number
- ES2253786T3 ES2253786T3 ES97942316T ES97942316T ES2253786T3 ES 2253786 T3 ES2253786 T3 ES 2253786T3 ES 97942316 T ES97942316 T ES 97942316T ES 97942316 T ES97942316 T ES 97942316T ES 2253786 T3 ES2253786 T3 ES 2253786T3
- Authority
- ES
- Spain
- Prior art keywords
- indole
- dihydro
- chloromethyl
- mmol
- benz
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 82
- 239000003814 drug Substances 0.000 title description 15
- 229940079593 drug Drugs 0.000 title description 14
- 239000002243 precursor Substances 0.000 title description 4
- 102000004459 Nitroreductase Human genes 0.000 claims abstract description 22
- 108020001162 nitroreductase Proteins 0.000 claims abstract description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims abstract description 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 219
- 239000000203 mixture Substances 0.000 claims description 87
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 80
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 80
- -1 5,6,7-trimethoxyindole-2-yl Chemical group 0.000 claims description 57
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 56
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 40
- 206010028980 Neoplasm Diseases 0.000 claims description 28
- 239000013598 vector Substances 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 9
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- DQUZJKNVYSYKDE-UHFFFAOYSA-N methyl 8-(chloromethyl)-4-nitro-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CCl)C4=C5C=C(NC5=C([N+]([O-])=O)C=C43)C(=O)OC)=CC2=C1 DQUZJKNVYSYKDE-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 230000001613 neoplastic effect Effects 0.000 claims description 5
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 4
- MAMMFIUMKJUAKQ-UHFFFAOYSA-N methyl 8-(chloromethyl)-4-(dimethylamino)-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CCl)C4=C5C=C(NC5=C(N(C)C)C=C43)C(=O)OC)=CC2=C1 MAMMFIUMKJUAKQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- GYUFCODDHMVUKY-UHFFFAOYSA-N methyl 8-(chloromethyl)-4-(methylamino)-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C=4C=C(C=5NC(=CC=5C=4C(CCl)C3)C(=O)OC)NC)=CC2=C1 GYUFCODDHMVUKY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 1
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Chemical group O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 abstract description 39
- 108090000790 Enzymes Proteins 0.000 abstract description 39
- 150000001412 amines Chemical class 0.000 abstract description 9
- 108010006303 Carboxypeptidases Proteins 0.000 abstract description 7
- 102000005367 Carboxypeptidases Human genes 0.000 abstract description 7
- 125000000168 pyrrolyl group Chemical group 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 388
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
- 239000000243 solution Substances 0.000 description 125
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 124
- 239000000460 chlorine Substances 0.000 description 124
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- 239000007787 solid Substances 0.000 description 62
- 238000000921 elemental analysis Methods 0.000 description 57
- 239000003208 petroleum Substances 0.000 description 51
- 239000002253 acid Substances 0.000 description 41
- 230000002829 reductive effect Effects 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- 238000002360 preparation method Methods 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 238000010992 reflux Methods 0.000 description 32
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 239000000284 extract Substances 0.000 description 27
- 229940002612 prodrug Drugs 0.000 description 25
- 239000000651 prodrug Substances 0.000 description 25
- 239000007832 Na2SO4 Substances 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- 239000002244 precipitate Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 19
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 229910019020 PtO2 Inorganic materials 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 12
- 238000010511 deprotection reaction Methods 0.000 description 12
- 238000010828 elution Methods 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- 229910002091 carbon monoxide Inorganic materials 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 239000008096 xylene Substances 0.000 description 11
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000002502 liposome Substances 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 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 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 7
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
- 239000011736 potassium bicarbonate Substances 0.000 description 7
- 235000015497 potassium bicarbonate Nutrition 0.000 description 7
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 7
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- JZMUJQGIASARGH-UHFFFAOYSA-N 5,6,7-trimethoxy-1h-indole-2-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC2=C1NC(C(O)=O)=C2 JZMUJQGIASARGH-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 241000701161 unidentified adenovirus Species 0.000 description 6
- INCAQIRDTKGRNM-UHFFFAOYSA-N 2-cyclopropyl-1h-indole Chemical class C1CC1C1=CC2=CC=CC=C2N1 INCAQIRDTKGRNM-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 125000001931 aliphatic group Chemical group 0.000 description 5
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 108010062699 gamma-Glutamyl Hydrolase Proteins 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- IMGLSHLXZGIZRU-UHFFFAOYSA-N (4-methoxyphenyl)methyl 1-hydroxy-4-nitronaphthalene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=CC([N+]([O-])=O)=C(C=CC=C2)C2=C1O IMGLSHLXZGIZRU-UHFFFAOYSA-N 0.000 description 4
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical class C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 4
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- ASWXNYNXAOQCCD-UHFFFAOYSA-N dichloro(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Cl)(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 ASWXNYNXAOQCCD-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- JFCQEDHGNNZCLN-UHFFFAOYSA-L glutarate(2-) Chemical compound [O-]C(=O)CCCC([O-])=O JFCQEDHGNNZCLN-UHFFFAOYSA-L 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- RXYCUKSOYJWGPE-UHFFFAOYSA-N methyl 2-azidoacetate Chemical compound COC(=O)CN=[N+]=[N-] RXYCUKSOYJWGPE-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 150000003738 xylenes Chemical class 0.000 description 4
- MHSGOABISYIYKP-UHFFFAOYSA-N (4-nitrophenyl)methyl carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(COC(Cl)=O)C=C1 MHSGOABISYIYKP-UHFFFAOYSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-O 1-methylimidazole Chemical compound CN1C=C[NH+]=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-O 0.000 description 3
- GQTIAGAYLRMEHQ-UHFFFAOYSA-N 3-formyl-2-hydroxy-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC(C=O)=C1O GQTIAGAYLRMEHQ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 101100441092 Danio rerio crlf3 gene Proteins 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- 229910006124 SOCl2 Inorganic materials 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- VQXINLNPICQTLR-UHFFFAOYSA-N carbonyl diazide Chemical compound [N-]=[N+]=NC(=O)N=[N+]=[N-] VQXINLNPICQTLR-UHFFFAOYSA-N 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- AQRVKOAIXZBVCJ-UHFFFAOYSA-N methyl 4-amino-8-(chloromethyl)-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CCl)C4=C5C=C(NC5=C(N)C=C43)C(=O)OC)=CC2=C1 AQRVKOAIXZBVCJ-UHFFFAOYSA-N 0.000 description 3
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 3
- 150000007523 nucleic acids Chemical group 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 235000021395 porridge Nutrition 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 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 3
- 238000006467 substitution reaction Methods 0.000 description 3
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 3
- LZPYYIKBDKBSTA-UHFFFAOYSA-N (2-iodo-3-nitrophenyl)methanol Chemical compound OCC1=CC=CC([N+]([O-])=O)=C1I LZPYYIKBDKBSTA-UHFFFAOYSA-N 0.000 description 2
- HYZNAHCBJSMZLR-UHFFFAOYSA-N (2-iodo-3-nitrophenyl)methyl acetate Chemical compound CC(=O)OCC1=CC=CC([N+]([O-])=O)=C1I HYZNAHCBJSMZLR-UHFFFAOYSA-N 0.000 description 2
- CXCORYBQTWAYEO-UHFFFAOYSA-N (3-amino-2-iodophenyl)methyl acetate Chemical compound CC(=O)OCC1=CC=CC(N)=C1I CXCORYBQTWAYEO-UHFFFAOYSA-N 0.000 description 2
- ARNUMSOEZWTGTP-UHFFFAOYSA-N (4-methoxyphenyl)methyl 1-hydroxynaphthalene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=CC=C(C=CC=C2)C2=C1O ARNUMSOEZWTGTP-UHFFFAOYSA-N 0.000 description 2
- YNIMPWMWPYPERB-UHFFFAOYSA-N 1-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-3-[(4-methoxyphenyl)methyl]-4-nitronaphthalene-2-carboxylic acid Chemical compound COC1=CC=C(C=C1)CC2=C(C3=CC=CC=C3C(=C2C(=O)O)C(C(=O)OC)C(=O)OC)[N+](=O)[O-] YNIMPWMWPYPERB-UHFFFAOYSA-N 0.000 description 2
- OKXHHSORNQTRRW-UHFFFAOYSA-N 1-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-4-nitronaphthalene-2-carboxylic acid Chemical compound C1=CC=C2C(C(C(=O)OC)C(=O)OC)=C(C(O)=O)C=C([N+]([O-])=O)C2=C1 OKXHHSORNQTRRW-UHFFFAOYSA-N 0.000 description 2
- XGKIWLRDLSNCRB-UHFFFAOYSA-N 1-methyl-4-nitropyrrole-2-carbaldehyde Chemical compound CN1C=C([N+]([O-])=O)C=C1C=O XGKIWLRDLSNCRB-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylamino-1-chloro-ethane hydrochloride Natural products CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 2
- JNZXWLAEKYYPHA-UHFFFAOYSA-N 2-hydroxy-3-methyl-5-nitrobenzoic acid Chemical compound CC1=CC([N+]([O-])=O)=CC(C(O)=O)=C1O JNZXWLAEKYYPHA-UHFFFAOYSA-N 0.000 description 2
- XWOGTRRVKVPJSP-UHFFFAOYSA-N 2-iodo-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1I XWOGTRRVKVPJSP-UHFFFAOYSA-N 0.000 description 2
- LFOCPNZCWSZXJK-UHFFFAOYSA-N 3-amino-2-iodobenzaldehyde Chemical compound NC1=CC=CC(C=O)=C1I LFOCPNZCWSZXJK-UHFFFAOYSA-N 0.000 description 2
- WMAZMEXFZKFZPJ-UHFFFAOYSA-N 3-amino-4-iodo-1H-indole-2-carboxylic acid Chemical compound C1=CC2=C(C(=C1)I)C(=C(N2)C(=O)O)N WMAZMEXFZKFZPJ-UHFFFAOYSA-N 0.000 description 2
- OTXSQWJJLQYZMO-UHFFFAOYSA-N 3-o-tert-butyl 1-o,1-o'-dimethyl 5-nitro-2h-benzo[e]indole-1,1,3-tricarboxylate Chemical compound C1=CC=CC2=C3C(C(=O)OC)(C(=O)OC)CN(C(=O)OC(C)(C)C)C3=CC([N+]([O-])=O)=C21 OTXSQWJJLQYZMO-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
- FVHZNZGBURSDBX-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]-1h-indole-2-carboxylic acid;hydrochloride Chemical compound Cl.CN(C)CCOC1=CC=C2NC(C(O)=O)=CC2=C1 FVHZNZGBURSDBX-UHFFFAOYSA-N 0.000 description 2
- WKTSVUBPXMSWLQ-UHFFFAOYSA-N 6-o-tert-butyl 2-o-methyl 8-(hydroxymethyl)-4-nitro-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2,6-dicarboxylate Chemical compound [O-][N+](=O)C1=C2NC(C(=O)OC)=CC2=C2C(CO)CN(C(=O)OC(C)(C)C)C2=C1 WKTSVUBPXMSWLQ-UHFFFAOYSA-N 0.000 description 2
- RFDLQXYXVUIREH-UHFFFAOYSA-N 6-o-tert-butyl 2-o-methyl 8-(hydroxymethyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2,6-dicarboxylate Chemical compound C1=C2NC(C(=O)OC)=CC2=C2C(CO)CN(C(=O)OC(C)(C)C)C2=C1 RFDLQXYXVUIREH-UHFFFAOYSA-N 0.000 description 2
- LCTHWTATFCDQAZ-UHFFFAOYSA-N 6-o-tert-butyl 2-o-methyl 8-[(2,2,6,6-tetramethylpiperidin-1-yl)oxymethyl]-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2,6-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C2=CC=C3NC(C(=O)OC)=CC3=C2C1CON1C(C)(C)CCCC1(C)C LCTHWTATFCDQAZ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- FGFUBBNNYLNVLJ-UHFFFAOYSA-N indolone Natural products C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- ANFHFIAKJGLDJV-UHFFFAOYSA-N methyl 8-(chloromethyl)-4-[(4-nitrophenyl)methoxycarbonylamino]-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound C=12NC(C(=O)OC)=CC2=C2C(CCl)CN(C(=O)C=3NC4=C(OC)C(OC)=C(OC)C=C4C=3)C2=CC=1NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 ANFHFIAKJGLDJV-UHFFFAOYSA-N 0.000 description 2
- ALBYZHPKGIWYMA-UHFFFAOYSA-N methyl 8-(hydroxymethyl)-4-nitro-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CO)C4=C5C=C(NC5=C([N+]([O-])=O)C=C43)C(=O)OC)=CC2=C1 ALBYZHPKGIWYMA-UHFFFAOYSA-N 0.000 description 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 210000004882 non-tumor cell Anatomy 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- QHSBUSNRUYTBLO-UHFFFAOYSA-N 2-azido-3-[4-(2-chloroethoxy)-3-methoxyphenyl]prop-2-enoic acid Chemical compound COc1cc(C=C(N=[N+]=[N-])C(O)=O)ccc1OCCCl QHSBUSNRUYTBLO-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- IIUPTHVVXMBJMQ-UHFFFAOYSA-N 3-amino-6-chloro-n-(diaminomethylidene)-5-(dimethylamino)pyrazine-2-carboxamide;hydrochloride Chemical compound Cl.CN(C)C1=NC(N)=C(C(=O)N=C(N)N)N=C1Cl IIUPTHVVXMBJMQ-UHFFFAOYSA-N 0.000 description 1
- DCBNVCCDXRZXOX-UHFFFAOYSA-N 4-(2-chloroethoxy)-3-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OCCCl DCBNVCCDXRZXOX-UHFFFAOYSA-N 0.000 description 1
- CCCVQPGAXZNTIL-UHFFFAOYSA-N 4-[2-(dimethylamino)ethoxy]aniline Chemical compound CN(C)CCOC1=CC=C(N)C=C1 CCCVQPGAXZNTIL-UHFFFAOYSA-N 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- QAHUNXWGQVQHLT-UHFFFAOYSA-N 5-acetamido-1h-indole-2-carboxylic acid Chemical compound CC(=O)NC1=CC=C2NC(C(O)=O)=CC2=C1 QAHUNXWGQVQHLT-UHFFFAOYSA-N 0.000 description 1
- FVFILQVUFMEXBX-UHFFFAOYSA-N 5-methoxy-3-methyl-2-nitrophenol Chemical compound COC1=CC(C)=C([N+]([O-])=O)C(O)=C1 FVFILQVUFMEXBX-UHFFFAOYSA-N 0.000 description 1
- YEBJVSLNUMZXRJ-UHFFFAOYSA-N 5-methoxyindole-2-carboxylic acid Chemical compound COC1=CC=C2NC(C(O)=O)=CC2=C1 YEBJVSLNUMZXRJ-UHFFFAOYSA-N 0.000 description 1
- LHFOJSCXLFKDIR-UHFFFAOYSA-N 5-nitro-1h-indole-2-carboxylic acid Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)O)=CC2=C1 LHFOJSCXLFKDIR-UHFFFAOYSA-N 0.000 description 1
- PPZACKOLDOLONU-UHFFFAOYSA-N 6-(2-chloroethoxy)-5-methoxy-1h-indole-2-carboxylic acid Chemical compound C1=C(OCCCl)C(OC)=CC2=C1NC(C(O)=O)=C2 PPZACKOLDOLONU-UHFFFAOYSA-N 0.000 description 1
- WDUPJVJHMXQTHX-UHFFFAOYSA-N 6-[2-(dimethylamino)ethoxy]-5-methoxy-1h-indole-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=C(OCCN(C)C)C(OC)=CC2=C1NC(C(O)=O)=C2 WDUPJVJHMXQTHX-UHFFFAOYSA-N 0.000 description 1
- KQGCKRKNUGHNEI-UHFFFAOYSA-N 7-[2-(dimethylamino)ethoxy]-5-methoxy-1h-indole-2-carboxylic acid;hydrochloride Chemical compound Cl.COC1=CC(OCCN(C)C)=C2NC(C(O)=O)=CC2=C1 KQGCKRKNUGHNEI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 125000006847 BOC protecting group Chemical group 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101100532679 Caenorhabditis elegans scc-1 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910020366 ClO 4 Inorganic materials 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 241000031711 Cytophagaceae Species 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 230000007118 DNA alkylation Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 1
- 102100021023 Gamma-glutamyl hydrolase Human genes 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 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 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 125000000815 N-oxide group Chemical group 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- ISKQADXMHQSTHK-UHFFFAOYSA-N [4-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=C(CN)C=C1 ISKQADXMHQSTHK-UHFFFAOYSA-N 0.000 description 1
- SMLWNVQYWLODEU-UHFFFAOYSA-N [amino-(2-iodophenyl)methyl] acetate Chemical compound C(C)(=O)OC(C1=C(C=CC=C1)I)N SMLWNVQYWLODEU-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- BBZDXMBRAFTCAA-AREMUKBSSA-N carzelesin Chemical compound C1=2NC=C(C)C=2C([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)C3=CC4=CC=C(C=C4O3)N(CC)CC)=C2C=C1OC(=O)NC1=CC=CC=C1 BBZDXMBRAFTCAA-AREMUKBSSA-N 0.000 description 1
- 229950007509 carzelesin Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- GKZOTESPJQWNKZ-UHFFFAOYSA-N chlorosulfonylmethylidene(dimethyl)azanium Chemical compound C[N+](C)=CS(Cl)(=O)=O GKZOTESPJQWNKZ-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-UHFFFAOYSA-N 0.000 description 1
- QSQXPRJUZJUTIP-UHFFFAOYSA-N ethyl 5-[2-(dimethylamino)ethoxy]-1h-indole-2-carboxylate Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)OCC)=CC2=C1 QSQXPRJUZJUTIP-UHFFFAOYSA-N 0.000 description 1
- SYJFOPHTAQJBMP-UHFFFAOYSA-N ethyl 7-[2-(dimethylamino)ethoxy]-5-methoxy-1h-indole-2-carboxylate Chemical compound COC1=CC(OCCN(C)C)=C2NC(C(=O)OCC)=CC2=C1 SYJFOPHTAQJBMP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108010042430 galactose receptor Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- QRMNENFZDDYDEF-GOSISDBHSA-N methyl (8s)-8-(bromomethyl)-2-methyl-4-(4-methylpiperazine-1-carbonyl)oxy-6-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-7,8-dihydro-3h-pyrrolo[3,2-e]indole-1-carboxylate Chemical compound C1([C@H](CBr)CN(C1=C1)C(=O)C=2NC3=C(OC)C(OC)=C(OC)C=C3C=2)=C2C(C(=O)OC)=C(C)NC2=C1OC(=O)N1CCN(C)CC1 QRMNENFZDDYDEF-GOSISDBHSA-N 0.000 description 1
- OKFSZCXMVHNSGZ-ONEGZZNKSA-N methyl (e)-3-(1-methyl-4-nitropyrrol-2-yl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC([N+]([O-])=O)=CN1C OKFSZCXMVHNSGZ-ONEGZZNKSA-N 0.000 description 1
- CCZSKIJGGMGMML-VOTSOKGWSA-N methyl (e)-3-[4-(butanoylamino)-1-methylpyrrol-2-yl]prop-2-enoate Chemical compound CCCC(=O)NC=1C=C(\C=C\C(=O)OC)N(C)C=1 CCZSKIJGGMGMML-VOTSOKGWSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- SPWSLPYCDDUJPE-UHFFFAOYSA-N methyl 6-(2-chloroethoxy)-5-methoxy-1h-indole-2-carboxylate Chemical compound COC1=C(OCCCl)C=C2NC(C(=O)OC)=CC2=C1 SPWSLPYCDDUJPE-UHFFFAOYSA-N 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- HHQJWDKIRXRTLS-UHFFFAOYSA-N n'-bromobutanediamide Chemical compound NC(=O)CCC(=O)NBr HHQJWDKIRXRTLS-UHFFFAOYSA-N 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- VLZLOWPYUQHHCG-UHFFFAOYSA-N nitromethylbenzene Chemical compound [O-][N+](=O)CC1=CC=CC=C1 VLZLOWPYUQHHCG-UHFFFAOYSA-N 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 150000008223 ribosides Chemical class 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005758 transcription activity Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9619082 | 1996-09-12 | ||
| GBGB9619082.2A GB9619082D0 (en) | 1996-09-12 | 1996-09-12 | Further cyclopropylindoles and their seco precursors,and their use as prodrugs |
| GB9707394 | 1997-04-10 | ||
| GBGB9707394.4A GB9707394D0 (en) | 1997-04-10 | 1997-04-10 | Further cyclopropylindoles and their seco precursors, and their use as prodrugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2253786T3 true ES2253786T3 (es) | 2006-06-01 |
Family
ID=26310030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97942316T Expired - Lifetime ES2253786T3 (es) | 1996-09-12 | 1997-09-12 | Compuestos de ciclopropilindola y su uso como precursores de medicamentos. |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0938474B1 (OSRAM) |
| JP (1) | JP4155598B2 (OSRAM) |
| AT (1) | ATE310725T1 (OSRAM) |
| AU (1) | AU721037B2 (OSRAM) |
| CA (1) | CA2265874C (OSRAM) |
| DE (1) | DE69734722T2 (OSRAM) |
| ES (1) | ES2253786T3 (OSRAM) |
| NZ (1) | NZ334344A (OSRAM) |
| WO (1) | WO1998011101A2 (OSRAM) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9818730D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
| ES2260570T3 (es) | 1998-08-27 | 2006-11-01 | Spirogen Limited | Pirrolobenziodiazepinas dimericas. |
| GB9909612D0 (en) * | 1999-04-26 | 1999-06-23 | Cancer Res Campaign Tech | N-protected amines and their use as prodrugs |
| US6909006B1 (en) * | 1999-08-27 | 2005-06-21 | Spirogen Limited | Cyclopropylindole derivatives |
| BR0110414A (pt) * | 2000-04-28 | 2003-02-11 | Baxter Healthcare Sa | Derivados de 2-acil indol e seu uso como agentes antitumores |
| WO2001083448A2 (de) * | 2000-05-02 | 2001-11-08 | Tietze Lutz F | Neue prodrugs von 6-hydroxy-2,3-dihydro-1h-indolen, 5-hydroxy-1,2-dihydro-3h-pyrrolo[3,2-e]indolen und 5-hydroxy-1,2-dihydro-3h-benzo[e]indolen sowie von 6-hydroxy-1,2,3,4-tetrahydro-benzo[f]chinolin-derivaten für eine selektive krebstherapie |
| DE60211905T2 (de) * | 2001-02-22 | 2007-01-18 | School Of Pharmacy, University Of London | Benz-indol- und benzo-chinolin-derivate als prodrugs zur tumorbehandlung |
| US7235578B2 (en) * | 2002-05-17 | 2007-06-26 | Auckland Uniservices Limited | Processes for preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl-(amine-derived)] compounds and analogues thereof, and to products obtained therefrom |
| GB0226593D0 (en) | 2002-11-14 | 2002-12-24 | Consultants Ltd | Compounds |
| US20050032868A1 (en) * | 2003-05-02 | 2005-02-10 | Garofalo Albert W. | Selected substituted pyrazole derivatives and related compounds as bradykinin B1 receptor antagonists |
| TW200509910A (en) | 2003-05-02 | 2005-03-16 | Elan Pharm Inc | Substituted pyrazole derivatives and related compounds as bradykinin B1 receptor antagonists |
| GB0321295D0 (en) | 2003-09-11 | 2003-10-15 | Spirogen Ltd | Synthesis of protected pyrrolobenzodiazepines |
| NZ536107A (en) * | 2004-10-22 | 2007-06-29 | Auckland Uniservices Ltd | Nitrobenzindoles and their use in cancer therapy |
| WO2007059404A2 (en) * | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
| US8940784B2 (en) * | 2006-02-02 | 2015-01-27 | Syntarga B.V. | Water-soluble CC-1065 analogs and their conjugates |
| WO2008039087A2 (en) * | 2006-09-29 | 2008-04-03 | Auckland Uniservices Limited | Indoline derivatives and uses thereof |
| TWI412367B (zh) | 2006-12-28 | 2013-10-21 | Medarex Llc | 化學鏈接劑與可裂解基質以及其之綴合物 |
| TW200900059A (en) | 2007-02-21 | 2009-01-01 | Medarex Inc | Chemical linkers with single amino acids and conjugates thereof |
| US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| RU2562232C2 (ru) | 2008-11-03 | 2015-09-10 | Синтарга Б.В. | Новые аналоги сс-1065 и их конъюгаты |
| DE102009051438A1 (de) | 2009-10-30 | 2011-05-05 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts | Fluoreszenzfarbstoffe |
| HUE030846T2 (en) | 2010-04-21 | 2017-06-28 | Syntarga Bv | Conjugates of cc-1065 analogs and bifunctional linkers |
| PL3092010T3 (pl) | 2014-01-10 | 2019-01-31 | Synthon Biopharmaceuticals B.V. | Sposób oczyszczania połączonych cysteiną koniugatów przeciwciało-lek |
| JP6224268B2 (ja) | 2014-01-10 | 2017-11-01 | シントン・バイオファーマシューティカルズ・ビー．ブイ．Ｓｙｎｔｈｏｎ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｂ．Ｖ． | 子宮内膜癌の治療において使用するためのデュオカルマイシンａｄｃ |
| HRP20160697T1 (hr) | 2014-01-10 | 2016-07-15 | Synthon Biopharmaceuticals B.V. | Duokarmicin adcs koji pokazuje poboljšanu antitumorsku aktivnost in vivo |
| CN108653288B (zh) * | 2018-05-29 | 2020-05-05 | 福建医科大学孟超肝胆医院(福州市传染病医院) | 一种乏氧响应聚合物纳米粒及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2598819B2 (ja) * | 1986-12-19 | 1997-04-09 | ジ・アップジョン・カンパニー | 新規なｃｃ‐１０６５同族体 |
| JP2642165B2 (ja) * | 1988-07-22 | 1997-08-20 | 協和醗酵工業株式会社 | 新規ｄｃ−８９化合物およびその製造法 |
| KR100208957B1 (ko) * | 1990-04-25 | 1999-07-15 | 로렌스 티. 마이젠헬더 | 신규한 cc-1065 유사체 |
| GB9516943D0 (en) * | 1995-08-18 | 1995-10-18 | Cancer Soc Auckland Div Nz Inc | Novel cyclopropylindoles and their secoprecursors,and their use as prodrugs |
| US6548530B1 (en) * | 1995-10-03 | 2003-04-15 | The Scripps Research Institute | CBI analogs of CC-1065 and the duocarmycins |
| EP0888301B1 (en) * | 1996-03-08 | 2005-08-10 | The Scripps Research Institute | Mcbi analogs of cc-1065 and the duocarmycins |
-
1997
- 1997-09-12 AT AT97942316T patent/ATE310725T1/de not_active IP Right Cessation
- 1997-09-12 WO PCT/NZ1997/000117 patent/WO1998011101A2/en not_active Ceased
- 1997-09-12 AU AU44039/97A patent/AU721037B2/en not_active Ceased
- 1997-09-12 ES ES97942316T patent/ES2253786T3/es not_active Expired - Lifetime
- 1997-09-12 NZ NZ334344A patent/NZ334344A/xx unknown
- 1997-09-12 CA CA002265874A patent/CA2265874C/en not_active Expired - Fee Related
- 1997-09-12 DE DE69734722T patent/DE69734722T2/de not_active Expired - Fee Related
- 1997-09-12 EP EP97942316A patent/EP0938474B1/en not_active Expired - Lifetime
- 1997-09-12 JP JP53749297A patent/JP4155598B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4155598B2 (ja) | 2008-09-24 |
| EP0938474A2 (en) | 1999-09-01 |
| WO1998011101A2 (en) | 1998-03-19 |
| AU721037B2 (en) | 2000-06-22 |
| AU4403997A (en) | 1998-04-02 |
| CA2265874A1 (en) | 1998-03-19 |
| CA2265874C (en) | 2007-08-28 |
| DE69734722D1 (de) | 2005-12-29 |
| WO1998011101A3 (en) | 1998-04-23 |
| EP0938474B1 (en) | 2005-11-23 |
| JP2000517292A (ja) | 2000-12-26 |
| DE69734722T2 (de) | 2006-07-20 |
| NZ334344A (en) | 2000-08-25 |
| ATE310725T1 (de) | 2005-12-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2253786T3 (es) | Compuestos de ciclopropilindola y su uso como precursores de medicamentos. | |
| US6130237A (en) | Condensed N-aclyindoles as antitumor agents | |
| US5985909A (en) | Cyclopropylindoles and their seco precursors, and their use as prodrugs | |
| ES2371191T3 (es) | Compuestos citotóxicos. | |
| JP4669611B2 (ja) | 化合物 | |
| ES2764523T3 (es) | Compuestos de 7-feniletilamino-4H-pirimido[4,5-D][1,3]oxazin-2-ona y su uso como inhibidores de IDH1 mutantes | |
| EP3458069B1 (en) | Pyrrolobenzodiazepines and conjugates thereof | |
| BRPI0712167A2 (pt) | compostos de aziridinil-epotilona | |
| BRPI0712165A2 (pt) | conjugado de análogos de aziridinil-eptiolona, composições farmacêuticas compreendendo os mesmos e usos dos mesmos | |
| NZ515044A (en) | N-protected amines and their use as prodrugs | |
| CN101044114B (zh) | 硝基苯并吲哚和它们在癌症疗法中的用途 | |
| US7235578B2 (en) | Processes for preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl-(amine-derived)] compounds and analogues thereof, and to products obtained therefrom | |
| US6251933B1 (en) | Seco precursors of cyclopropylindolines and their use as prodrugs | |
| EP0944596B1 (en) | 1-acryloylindoline derivatives and their use as prodrugs of anticancer agents | |
| ES2882531T3 (es) | Compuesto anti-virus CMVH | |
| JPH08151380A (ja) | ビス（トリフルオロメチルピロロインドールカルボン酸エステル）誘導体及びその製造方法 | |
| JPH0834787A (ja) | ピロロカルバゾール誘導体及びその製造方法 |