JPH11513391A - Ｃｃ−１０６５ 及びズオカーマイシンのｃｂｉ 類縁体 - Google Patents
Ｃｃ−１０６５ 及びズオカーマイシンのｃｂｉ 類縁体Info
- Publication number
- JPH11513391A JPH11513391A JP9514522A JP51452297A JPH11513391A JP H11513391 A JPH11513391 A JP H11513391A JP 9514522 A JP9514522 A JP 9514522A JP 51452297 A JP51452297 A JP 51452297A JP H11513391 A JPH11513391 A JP H11513391A
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl
- structural formula
- following structural
- cbi
- 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.)
- Abandoned
Links
- 229960005532 CC-1065 Drugs 0.000 title abstract description 33
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 title abstract description 22
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 title abstract description 16
- 229960005501 duocarmycin Drugs 0.000 title abstract description 11
- 229930184221 duocarmycin Natural products 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 84
- -1 N-substituted pyrrolidine ring Chemical group 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 58
- 150000002431 hydrogen Chemical class 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 239000000460 chlorine Substances 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 3
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
- HOEFWOBLOGZQIQ-UHFFFAOYSA-N morpholin-4-yl morpholine-4-carbodithioate Chemical group C1COCCN1C(=S)SN1CCOCC1 HOEFWOBLOGZQIQ-UHFFFAOYSA-N 0.000 claims description 3
- 150000003235 pyrrolidines Chemical class 0.000 claims 2
- 239000003814 drug Substances 0.000 abstract description 107
- 229940079593 drug Drugs 0.000 abstract description 105
- 108020004414 DNA Proteins 0.000 abstract description 46
- 230000001472 cytotoxic effect Effects 0.000 abstract description 38
- 231100000433 cytotoxic Toxicity 0.000 abstract description 26
- 230000004568 DNA-binding Effects 0.000 abstract description 23
- UIGRBLXJJABSCB-UHFFFAOYSA-N benzo[e]indol-4-one Chemical compound O=C1C=C2C=CC=CC2=C2C1=NC=C2 UIGRBLXJJABSCB-UHFFFAOYSA-N 0.000 abstract description 21
- 230000003389 potentiating effect Effects 0.000 abstract description 19
- 230000000259 anti-tumor effect Effects 0.000 abstract description 12
- 230000002152 alkylating effect Effects 0.000 abstract description 10
- 238000000338 in vitro Methods 0.000 abstract description 10
- 230000001965 increasing effect Effects 0.000 abstract description 9
- 230000004048 modification Effects 0.000 abstract description 7
- 238000012986 modification Methods 0.000 abstract description 7
- 239000003242 anti bacterial agent Substances 0.000 abstract description 6
- 229940088710 antibiotic agent Drugs 0.000 abstract description 6
- VQNATVDKACXKTF-UHFFFAOYSA-N Duocarmycin SA Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C(C64CC6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-UHFFFAOYSA-N 0.000 abstract description 3
- 229960005510 duocarmycin SA Drugs 0.000 abstract description 3
- 230000009897 systematic effect Effects 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 104
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 84
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- 238000005481 NMR spectroscopy Methods 0.000 description 76
- 238000002360 preparation method Methods 0.000 description 63
- 239000000243 solution Substances 0.000 description 53
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 48
- XQRJFEVDQXEIAX-JFYQDRLCSA-M cobinamide Chemical class [Co]N([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@H](O)C)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O XQRJFEVDQXEIAX-JFYQDRLCSA-M 0.000 description 48
- 239000000203 mixture Substances 0.000 description 48
- 239000007787 solid Substances 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 42
- 239000002904 solvent Substances 0.000 description 39
- 230000007118 DNA alkylation Effects 0.000 description 34
- 238000005804 alkylation reaction Methods 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 235000019876 cocoa butter improver Nutrition 0.000 description 33
- 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 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- 238000003818 flash chromatography Methods 0.000 description 31
- 230000029936 alkylation Effects 0.000 description 29
- 238000000034 method Methods 0.000 description 28
- 239000012298 atmosphere Substances 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 27
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 26
- 229920003211 cis-1,4-polyisoprene Polymers 0.000 description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
- 238000003797 solvolysis reaction Methods 0.000 description 22
- 238000000354 decomposition reaction Methods 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 239000007864 aqueous solution Substances 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- 238000010828 elution Methods 0.000 description 17
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 17
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 14
- 230000027455 binding Effects 0.000 description 14
- 238000009739 binding Methods 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 230000009257 reactivity Effects 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 230000003013 cytotoxicity Effects 0.000 description 12
- 231100000135 cytotoxicity Toxicity 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000005119 centrifugation Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
- 230000002441 reversible effect Effects 0.000 description 10
- 230000006641 stabilisation Effects 0.000 description 10
- 238000011105 stabilization Methods 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 9
- 125000005605 benzo group Chemical group 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 235000018734 Sambucus australis Nutrition 0.000 description 8
- 244000180577 Sambucus australis Species 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 8
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 229930014626 natural product Natural products 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 229930024421 Adenine Natural products 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229960000643 adenine Drugs 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 5
- 239000000370 acceptor Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 238000000376 autoradiography Methods 0.000 description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 230000003111 delayed effect Effects 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000006265 spirocyclization reaction Methods 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108020005124 DNA Adducts Proteins 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- YXDYHFYQRLFAFN-UHFFFAOYSA-N methyl 6-nitro-1h-benzimidazole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)OC)=NC2=C1 YXDYHFYQRLFAFN-UHFFFAOYSA-N 0.000 description 4
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 4
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000006798 ring closing metathesis reaction Methods 0.000 description 4
- 230000007017 scission 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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 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 3
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 239000007984 Tris EDTA buffer Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- VJAMBZRWYAAZSN-UHFFFAOYSA-N bis(2,4-dinitrophenyl) carbonate Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC=C1OC(=O)OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O VJAMBZRWYAAZSN-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 229940126543 compound 14 Drugs 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 230000009881 electrostatic interaction Effects 0.000 description 3
- 238000012869 ethanol precipitation Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 3
- RXYCUKSOYJWGPE-UHFFFAOYSA-N methyl 2-azidoacetate Chemical compound COC(=O)CN=[N+]=[N-] RXYCUKSOYJWGPE-UHFFFAOYSA-N 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- WYURNTSHIVDZCO-SVYQBANQSA-N oxolane-d8 Chemical compound [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- KYCVRKPFNLCHLL-UHFFFAOYSA-N tert-butyl 5-aminoindole-1-carboxylate Chemical compound NC1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 KYCVRKPFNLCHLL-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
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- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- AZVARJHZBXHUSO-DZQVEHCYSA-N methyl (1R,4R,12S)-4-methyl-3,7-dioxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),8-diene-4-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 AZVARJHZBXHUSO-DZQVEHCYSA-N 0.000 description 1
- NQPIEWBAWBFGOB-UHFFFAOYSA-N methyl 1h-indole-2-carboxylate Chemical class C1=CC=C2NC(C(=O)OC)=CC2=C1 NQPIEWBAWBFGOB-UHFFFAOYSA-N 0.000 description 1
- IBQIXBZOZOCHFI-UHFFFAOYSA-N methyl 3-(2-azidophenyl)prop-2-enoate Chemical compound COC(=O)C=CC1=CC=CC=C1N=[N+]=[N-] IBQIXBZOZOCHFI-UHFFFAOYSA-N 0.000 description 1
- KRPDKDKJKIBCBX-UHFFFAOYSA-N methyl 5-amino-1h-indole-2-carboxylate Chemical compound NC1=CC=C2NC(C(=O)OC)=CC2=C1 KRPDKDKJKIBCBX-UHFFFAOYSA-N 0.000 description 1
- PTZVWKVAXNDAIR-UHFFFAOYSA-N methyl 5-nitro-1h-indole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)OC)=CC2=C1 PTZVWKVAXNDAIR-UHFFFAOYSA-N 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- PUPKPAZSFZOLOR-UHFFFAOYSA-N n,n-dimethylformamide;toluene Chemical compound CN(C)C=O.CC1=CC=CC=C1 PUPKPAZSFZOLOR-UHFFFAOYSA-N 0.000 description 1
- UPBAOYRENQEPJO-UHFFFAOYSA-N n-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide Chemical compound CN1C=C(NC=O)C=C1C(=O)NC1=CN(C)C(C(=O)NC2=CN(C)C(C(=O)NCCC(N)=N)=C2)=C1 UPBAOYRENQEPJO-UHFFFAOYSA-N 0.000 description 1
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 description 1
- XOOMNEFVDUTJPP-UHFFFAOYSA-N naphthalene-1,3-diol Chemical compound C1=CC=CC2=CC(O)=CC(O)=C21 XOOMNEFVDUTJPP-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- OJPNKYLDSDFUPG-UHFFFAOYSA-N p-quinomethane Chemical class C=C1C=CC(=O)C=C1 OJPNKYLDSDFUPG-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical class OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- YZHUMGUJCQRKBT-UHFFFAOYSA-M sodium chlorate Chemical compound [Na+].[O-]Cl(=O)=O YZHUMGUJCQRKBT-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 108010042747 stallimycin Proteins 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- LZOZLBFZGFLFBV-UHFFFAOYSA-N sulfene Chemical compound C=S(=O)=O LZOZLBFZGFLFBV-UHFFFAOYSA-N 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000001429 visible spectrum Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 101150061972 zur gene Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- 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
- C07D209/96—Spiro-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US475295P | 1995-10-03 | 1995-10-03 | |
| US60/004,752 | 1995-10-03 | ||
| PCT/US1996/016481 WO1997012862A1 (en) | 1995-10-03 | 1996-10-03 | Cbi analogs of cc-1065 and the duocarmycins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH11513391A true JPH11513391A (ja) | 1999-11-16 |
| JPH11513391A5 JPH11513391A5 (https=) | 2004-10-14 |
Family
ID=21712350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9514522A Abandoned JPH11513391A (ja) | 1995-10-03 | 1996-10-03 | Ｃｃ−１０６５ 及びズオカーマイシンのｃｂｉ 類縁体 |
Country Status (7)
| Country | Link |
|---|---|
| US (3) | US6548530B1 (https=) |
| EP (1) | EP0862553A4 (https=) |
| JP (1) | JPH11513391A (https=) |
| AU (1) | AU727608B2 (https=) |
| CA (1) | CA2233936A1 (https=) |
| NZ (1) | NZ321172A (https=) |
| WO (1) | WO1997012862A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009513676A (ja) * | 2005-10-26 | 2009-04-02 | メダレックス インコーポレイテッド | Ｃｃ−１０６５類似体の調製方法及び調製用化合物 |
| JP2016515577A (ja) * | 2013-03-28 | 2016-05-30 | ザ スクリプス リサーチ インスティテュート | 環状ｎ−アシルｏ−アミノフェノールｃｂｉ誘導体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843937A (en) * | 1996-05-23 | 1998-12-01 | Panorama Research, Inc. | DNA-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents |
| AU721037B2 (en) * | 1996-09-12 | 2000-06-22 | Auckland Uniservices Limited | Condensed N-acylindoles as antitumor agents |
| US6130237A (en) * | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
| EP1408960B1 (en) | 2001-02-22 | 2006-05-31 | School Of Pharmacy, University Of London | Benz-indole and benzo-quinoline derivatives as prodrugs for tumour treatment |
| DE10121215A1 (de) * | 2001-04-30 | 2002-10-31 | Merck Patent Gmbh | Dihydro-imidazo[4,5-e]indol- und 7H-Pyrrolo[3,2-f]chinoxalin Derivate als nikotinische Acetylcholinrezeptor Liganden und/oder serotonerge Liganden |
| DE10121217A1 (de) * | 2001-04-30 | 2002-10-31 | Merck Patent Gmbh | 6H-Oxazolo[4,5-e]indol-Derivate als nikotinische Acetylcholinrezeptor Liganden und/oder serotonerge Liganden |
| AU2002311919B8 (en) | 2001-05-11 | 2007-03-22 | Ludwig Institute For Cancer Research Ltd | Specific binding proteins and uses thereof |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| US6989452B2 (en) * | 2001-05-31 | 2006-01-24 | Medarex, Inc. | Disulfide prodrugs and linkers and stabilizers useful therefor |
| CA2460345A1 (en) | 2001-09-13 | 2003-03-20 | Synta Pharmaceuticals Corp. | 2-aroylimidazole compounds for treating cancer |
| US6756397B2 (en) * | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
| JP4806680B2 (ja) * | 2004-05-19 | 2011-11-02 | メダレックス インコーポレイテッド | 自己犠牲リンカー及び薬剤複合体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843937A (en) * | 1996-05-23 | 1998-12-01 | Panorama Research, Inc. | DNA-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents |
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1996
- 1996-10-03 AU AU74315/96A patent/AU727608B2/en not_active Ceased
- 1996-10-03 WO PCT/US1996/016481 patent/WO1997012862A1/en not_active Ceased
- 1996-10-03 NZ NZ321172A patent/NZ321172A/en unknown
- 1996-10-03 US US09/051,264 patent/US6548530B1/en not_active Expired - Fee Related
- 1996-10-03 CA CA002233936A patent/CA2233936A1/en not_active Abandoned
- 1996-10-03 EP EP96936498A patent/EP0862553A4/en not_active Withdrawn
- 1996-10-03 JP JP9514522A patent/JPH11513391A/ja not_active Abandoned
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2003
- 2003-04-15 US US10/417,043 patent/US20040002528A1/en not_active Abandoned
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2004
- 2004-06-24 US US10/876,992 patent/US20050032860A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009513676A (ja) * | 2005-10-26 | 2009-04-02 | メダレックス インコーポレイテッド | Ｃｃ−１０６５類似体の調製方法及び調製用化合物 |
| JP2016515577A (ja) * | 2013-03-28 | 2016-05-30 | ザ スクリプス リサーチ インスティテュート | 環状ｎ−アシルｏ−アミノフェノールｃｂｉ誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ321172A (en) | 2000-02-28 |
| CA2233936A1 (en) | 1997-04-10 |
| US20050032860A1 (en) | 2005-02-10 |
| AU7431596A (en) | 1997-04-28 |
| WO1997012862A1 (en) | 1997-04-10 |
| US6548530B1 (en) | 2003-04-15 |
| EP0862553A4 (en) | 1999-02-03 |
| EP0862553A1 (en) | 1998-09-09 |
| US20040002528A1 (en) | 2004-01-01 |
| AU727608B2 (en) | 2000-12-14 |
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