NZ321172A - CBI analogs of CC-1065 and the duocarmycins - Google Patents

CBI analogs of CC-1065 and the duocarmycins

Info

Publication number: NZ321172A
Authority: NZ; New Zealand
Prior art keywords: alkyl; group; pyrrolidine ring; substituted pyrrolidine; hydrogen
Prior art date: 1995-10-03

Application number

NZ321172A

Other languages

English (en)

Inventor

Dale L Boger

Original Assignee

Scripps Research Inst

Priority date (The priority date 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 date listed.)

1995-10-03

Filing date

1996-10-03

Publication date

2000-02-28

1996-10-03 Application filed by Scripps Research Inst filed Critical Scripps Research Inst

2000-02-28 Publication of NZ321172A publication Critical patent/NZ321172A/en

Links

229960005532 CC-1065 Drugs 0.000 title abstract description 32
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
229960005501 duocarmycin Drugs 0.000 title abstract description 16
229930184221 duocarmycin Natural products 0.000 title abstract description 16
150000001875 compounds Chemical class 0.000 claims abstract description 54
-1 N-substituted pyrrolidine ring Chemical group 0.000 claims description 59
229910052739 hydrogen Inorganic materials 0.000 claims description 56
239000001257 hydrogen Substances 0.000 claims description 40
150000002431 hydrogen Chemical group 0.000 claims description 32
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
229910052799 carbon Inorganic materials 0.000 claims description 21
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 13
206010028980 Neoplasm Diseases 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
HOEFWOBLOGZQIQ-UHFFFAOYSA-N morpholin-4-yl morpholine-4-carbodithioate Chemical compound C1COCCN1C(=S)SN1CCOCC1 HOEFWOBLOGZQIQ-UHFFFAOYSA-N 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims 7
238000004519 manufacturing process Methods 0.000 claims 2
OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical compound [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 abstract description 126
238000005804 alkylation reaction Methods 0.000 abstract description 47
230000001472 cytotoxic effect Effects 0.000 abstract description 47
230000029936 alkylation Effects 0.000 abstract description 41
108020004414 DNA Proteins 0.000 abstract description 36
231100000433 cytotoxic Toxicity 0.000 abstract description 33
230000003389 potentiating effect Effects 0.000 abstract description 26
230000004568 DNA-binding Effects 0.000 abstract description 25
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 abstract description 21
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 14
230000000259 anti-tumor effect Effects 0.000 abstract description 12
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 11
229960005510 duocarmycin SA Drugs 0.000 abstract description 11
238000000338 in vitro Methods 0.000 abstract description 9
230000004048 modification Effects 0.000 abstract description 9
238000012986 modification Methods 0.000 abstract description 9
239000003242 anti bacterial agent Substances 0.000 abstract description 5
229940088710 antibiotic agent Drugs 0.000 abstract description 5
230000009897 systematic effect Effects 0.000 abstract description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 104
238000005481 NMR spectroscopy Methods 0.000 description 97
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 79
235000011468 Albizia julibrissin Nutrition 0.000 description 73
241001070944 Mimosa Species 0.000 description 73
238000002360 preparation method Methods 0.000 description 66
239000000243 solution Substances 0.000 description 59
239000007787 solid Substances 0.000 description 47
230000007118 DNA alkylation Effects 0.000 description 46
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 43
230000036515 potency Effects 0.000 description 41
239000000203 mixture Substances 0.000 description 38
239000002904 solvent Substances 0.000 description 38
229910001868 water Inorganic materials 0.000 description 38
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
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 35
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 35
238000003818 flash chromatography Methods 0.000 description 33
238000013456 study Methods 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
229940093499 ethyl acetate Drugs 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 30
238000000034 method Methods 0.000 description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
239000000543 intermediate Substances 0.000 description 26
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
238000010828 elution Methods 0.000 description 25
230000027455 binding Effects 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 24
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 21
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 20
125000001424 substituent group Chemical group 0.000 description 20
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 17
238000003797 solvolysis reaction Methods 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 16
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
230000009257 reactivity Effects 0.000 description 16
101150041968 CDC13 gene Proteins 0.000 description 14
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
238000003786 synthesis reaction Methods 0.000 description 12
230000002441 reversible effect Effects 0.000 description 11
229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 10
201000011510 cancer Diseases 0.000 description 10
239000000758 substrate Substances 0.000 description 10
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 9
235000018734 Sambucus australis Nutrition 0.000 description 9
244000180577 Sambucus australis Species 0.000 description 9
125000005605 benzo group Chemical group 0.000 description 9
150000007942 carboxylates Chemical class 0.000 description 9
239000002243 precursor Substances 0.000 description 9
230000006641 stabilisation Effects 0.000 description 9
238000011105 stabilization Methods 0.000 description 9
230000000087 stabilizing effect Effects 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
230000004071 biological effect Effects 0.000 description 8
238000011156 evaluation Methods 0.000 description 8
238000001914 filtration Methods 0.000 description 8
150000003254 radicals Chemical class 0.000 description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 7
238000000376 autoradiography Methods 0.000 description 7
230000000368 destabilizing effect Effects 0.000 description 7
230000003993 interaction Effects 0.000 description 7
229930014626 natural product Natural products 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
239000011734 sodium Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
238000010521 absorption reaction Methods 0.000 description 6
230000002152 alkylating effect Effects 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
238000001035 drying Methods 0.000 description 6
239000000499 gel Substances 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
238000012163 sequencing technique Methods 0.000 description 6
229930024421 Adenine Natural products 0.000 description 5
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 5
229960000643 adenine Drugs 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
230000003111 delayed effect Effects 0.000 description 5
230000003292 diminished effect Effects 0.000 description 5
230000000694 effects Effects 0.000 description 5
230000002209 hydrophobic effect Effects 0.000 description 5
230000003834 intracellular effect Effects 0.000 description 5
150000004702 methyl esters Chemical class 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
239000007984 Tris EDTA buffer Substances 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
230000000052 comparative effect Effects 0.000 description 4
230000002860 competitive effect Effects 0.000 description 4
238000010511 deprotection reaction Methods 0.000 description 4
230000009881 electrostatic interaction Effects 0.000 description 4
UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 4
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
230000001965 increasing effect Effects 0.000 description 4
BEAHBHCSAFZHKO-UHFFFAOYSA-N methyl 5-amino-1,3-benzoxazole-2-carboxylate Chemical compound NC1=CC=C2OC(C(=O)OC)=NC2=C1 BEAHBHCSAFZHKO-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
239000012071 phase Substances 0.000 description 4
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 4
239000000843 powder Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
230000007017 scission Effects 0.000 description 4
238000001149 thermolysis Methods 0.000 description 4
230000001988 toxicity Effects 0.000 description 4
231100000419 toxicity Toxicity 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
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
238000013459 approach Methods 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
238000004587 chromatography analysis Methods 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
229940125797 compound 12 Drugs 0.000 description 3
229940126543 compound 14 Drugs 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
239000013078 crystal Substances 0.000 description 3
229940127089 cytotoxic agent Drugs 0.000 description 3
239000002254 cytotoxic agent Substances 0.000 description 3
231100000599 cytotoxic agent Toxicity 0.000 description 3
230000008034 disappearance Effects 0.000 description 3
238000012869 ethanol precipitation Methods 0.000 description 3
MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 3
238000007429 general method Methods 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
238000010348 incorporation Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000011835 investigation Methods 0.000 description 3
230000002427 irreversible effect Effects 0.000 description 3
239000010410 layer Substances 0.000 description 3
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 3
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 3
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
230000004962 physiological condition Effects 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000010992 reflux Methods 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
CNMDREPWSZVYGL-UHFFFAOYSA-N tert-butyl n-(1-iodo-4-phenylmethoxynaphthalen-2-yl)carbamate Chemical compound C=12C=CC=CC2=C(I)C(NC(=O)OC(C)(C)C)=CC=1OCC1=CC=CC=C1 CNMDREPWSZVYGL-UHFFFAOYSA-N 0.000 description 3
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
239000008096 xylene Substances 0.000 description 3
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
JHTQTAYWCUAENJ-UHFFFAOYSA-N 1,3-benzoxazole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1OC=N2 JHTQTAYWCUAENJ-UHFFFAOYSA-N 0.000 description 2
HCUARRIEZVDMPT-UHFFFAOYSA-M 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)[O-])=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-M 0.000 description 2
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 2
OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 2
ALGIYXGLGIECNT-UHFFFAOYSA-N 3h-benzo[e]indole Chemical compound C1=CC=C2C(C=CN3)=C3C=CC2=C1 ALGIYXGLGIECNT-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
108091029792 Alkylated DNA Proteins 0.000 description 2
UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 2
PLKJWVYBFAGRHG-UHFFFAOYSA-N C[N+](C1=CC=C2C=C(NC2=C1)C(=O)[O-])(C)C Chemical compound C[N+](C1=CC=C2C=C(NC2=C1)C(=O)[O-])(C)C PLKJWVYBFAGRHG-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
102000053602 DNA Human genes 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
239000008051 TBE buffer Substances 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
230000004075 alteration Effects 0.000 description 2
239000003972 antineoplastic antibiotic Substances 0.000 description 2
239000012062 aqueous buffer Substances 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
238000003556 assay Methods 0.000 description 2
UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
238000012925 biological evaluation Methods 0.000 description 2
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
239000004327 boric acid Substances 0.000 description 2
239000004202 carbamide Substances 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
238000006555 catalytic reaction Methods 0.000 description 2
229940125810 compound 20 Drugs 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000003013 cytotoxicity Effects 0.000 description 2
231100000135 cytotoxicity Toxicity 0.000 description 2
238000011161 development Methods 0.000 description 2
239000005546 dideoxynucleotide Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001962 electrophoresis Methods 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 2
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
KCKIKSJECTZLJA-UHFFFAOYSA-N indol-4-one Chemical compound O=C1C=CC=C2N=CC=C12 KCKIKSJECTZLJA-UHFFFAOYSA-N 0.000 description 2
NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 2
RXYCUKSOYJWGPE-UHFFFAOYSA-N methyl 2-azidoacetate Chemical compound COC(=O)CN=[N+]=[N-] RXYCUKSOYJWGPE-UHFFFAOYSA-N 0.000 description 2
OLLMSIUDBMURHQ-UHFFFAOYSA-N methyl 5-amino-1-benzofuran-2-carboxylate Chemical compound NC1=CC=C2OC(C(=O)OC)=CC2=C1 OLLMSIUDBMURHQ-UHFFFAOYSA-N 0.000 description 2
PSEIRKHMARZIRI-UHFFFAOYSA-N methyl 6-amino-1h-indole-2-carboxylate Chemical compound C1=C(N)C=C2NC(C(=O)OC)=CC2=C1 PSEIRKHMARZIRI-UHFFFAOYSA-N 0.000 description 2
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
239000004533 oil dispersion Substances 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000008188 pellet Substances 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
230000005588 protonation Effects 0.000 description 2
150000003242 quaternary ammonium salts Chemical class 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 2
238000003756 stirring Methods 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 2
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 2
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 2
238000010200 validation analysis Methods 0.000 description 2
239000003039 volatile agent Substances 0.000 description 2
238000003260 vortexing Methods 0.000 description 2
238000010792 warming Methods 0.000 description 2
SNYJVTXPSXNUSZ-FXTIPPFDSA-N (+)-cpi-cdpi2 Chemical compound C1=C2NC(C(=O)N3CCC4=C5C=C(NC5=CC=C43)C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)NC=C5C)=CC2=C2CCN(C(N)=O)C2=C1 SNYJVTXPSXNUSZ-FXTIPPFDSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
TYNSUEXNGLNQSS-UHFFFAOYSA-N 6-carbamoyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(N)=O TYNSUEXNGLNQSS-UHFFFAOYSA-N 0.000 description 1
BIUCOFQROHIAEO-UHFFFAOYSA-N 7-nitroindole-2-carboxylic acid Chemical compound C1=CC([N+]([O-])=O)=C2NC(C(=O)O)=CC2=C1 BIUCOFQROHIAEO-UHFFFAOYSA-N 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
101710136377 Cold shock-like protein CspH Proteins 0.000 description 1
206010013710 Drug interaction Diseases 0.000 description 1
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
239000011837 N,N-methylenebisacrylamide Substances 0.000 description 1
108091028043 Nucleic acid sequence Proteins 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical group 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
RNOAANRGEYCUQZ-UHFFFAOYSA-N azido acetate Chemical compound CC(=O)ON=[N+]=[N-] RNOAANRGEYCUQZ-UHFFFAOYSA-N 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
239000012965 benzophenone Substances 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
PITJNOYHDJOZBD-DLUDVSRJSA-N chembl307066 Chemical compound C12=CC(=O)C3=CC=CC=C3[C@@]31C[C@@H]3CN2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 PITJNOYHDJOZBD-DLUDVSRJSA-N 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000010835 comparative analysis Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
229940000406 drug candidate Drugs 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
239000000284 extract Substances 0.000 description 1
231100001264 fatal toxicity Toxicity 0.000 description 1
239000006260 foam Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
RJTZUHVCZIGJMB-UHFFFAOYSA-N hydron;1h-indole;chloride Chemical compound Cl.C1=CC=C2NC=CC2=C1 RJTZUHVCZIGJMB-UHFFFAOYSA-N 0.000 description 1
230000005917 in vivo anti-tumor 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
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
238000011068 loading method Methods 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000463 material Substances 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
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
238000002156 mixing Methods 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
239000002547 new drug Substances 0.000 description 1
KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
238000009520 phase I clinical trial Methods 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
BKOVMXWXILSWCU-UHFFFAOYSA-N pyrrolo[3,2-e]benzimidazole Chemical compound C1=CC2=NC=CC2=C2N=CN=C21 BKOVMXWXILSWCU-UHFFFAOYSA-N 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000008439 repair process Effects 0.000 description 1
238000003385 ring cleavage reaction Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
229910052708 sodium Inorganic materials 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
VVLFAAMTGMGYBS-UHFFFAOYSA-M sodium;4-[[4-(ethylamino)-3-methylphenyl]-(4-ethylimino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-3-sulfobenzenesulfonate Chemical compound [Na+].C1=C(C)C(NCC)=CC=C1C(C=1C(=CC(=CC=1)S([O-])(=O)=O)S(O)(=O)=O)=C1C=C(C)C(=NCC)C=C1 VVLFAAMTGMGYBS-UHFFFAOYSA-M 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
108010042747 stallimycin Proteins 0.000 description 1
239000007858 starting material Substances 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
238000010189 synthetic method Methods 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 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)

NZ321172A 1995-10-03 1996-10-03 CBI analogs of CC-1065 and the duocarmycins NZ321172A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US475295P	1995-10-03	1995-10-03
PCT/US1996/016481 WO1997012862A1 (en)	1995-10-03	1996-10-03	Cbi analogs of cc-1065 and the duocarmycins

Publications (1)

Publication Number	Publication Date
NZ321172A true NZ321172A (en)	2000-02-28

Family

ID=21712350

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NZ321172A NZ321172A (en)	1995-10-03	1996-10-03	CBI analogs of CC-1065 and the duocarmycins

Country Status (7)

Country	Link
US (3)	US6548530B1 (2)
EP (1)	EP0862553A4 (2)
JP (1)	JPH11513391A (2)
AU (1)	AU727608B2 (2)
CA (1)	CA2233936A1 (2)
NZ (1)	NZ321172A (2)
WO (1)	WO1997012862A1 (2)

Families Citing this family (94)

* Cited by examiner, † Cited by third party
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
US7691962B2 (en) *	2004-05-19	2010-04-06	Medarex, Inc.	Chemical linkers and conjugates thereof
US7393665B2 (en) *	2005-02-10	2008-07-01	Population Genetics Technologies Ltd	Methods and compositions for tagging and identifying polynucleotides
JP2008529556A (ja) *	2005-02-18	2008-08-07	メダレックス，インク．	前立腺特異的膜抗原（ｐｓｍａ）に対するヒトモノクローナル抗体
US7714016B2 (en) *	2005-04-08	2010-05-11	Medarex, Inc.	Cytotoxic compounds and conjugates with cleavable substrates
NZ566395A (en)	2005-09-26	2012-03-30	Medarex Inc	Human monoclonal antibodies to CD70
EP2354163A3 (en) *	2005-09-26	2013-04-24	Medarex, Inc.	Conjugates of duocarmycin and anti-CD70 or anti-PSMA antibodies
RS52100B (sr) *	2005-10-26	2012-06-30	Medarex, Inc.	Postupci i jedinjenja za pripremu analoga cc-1065
WO2007059404A2 (en)	2005-11-10	2007-05-24	Medarex, Inc.	Duocarmycin derivatives as novel cytotoxic compounds and conjugates
US8383118B2 (en)	2005-12-08	2013-02-26	Medarex, Inc.	Human monoclonal antibodies to fucosyl-GM1 and methods for using anti-fucosyl-GM1
EA017812B1 (ru)	2005-12-08	2013-03-29	Медарекс, Инк.	Выделенное моноклональное антитело или его антигенсвязывающий участок, которые связываются с протеинтирозинкиназой 7 ( ptk7) человека, и их применение
US20090175886A1 (en)	2006-01-17	2009-07-09	Medarex, Inc.	Monoclonal antibodies against cd30 lacking in fucosyl and xylosyl residues
CA2662350A1 (en)	2006-09-05	2008-03-13	Medarex, Inc.	Antibodies to bone morphogenic proteins and receptors therefor and methods for their use
US8481683B2 (en)	2006-12-01	2013-07-09	Medarex, Inc.	Human antibodies that bind CD22 and uses thereof
CL2007003622A1 (es)	2006-12-13	2009-08-07	Medarex Inc	Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales.
MX2009006277A (es)	2006-12-14	2009-07-24	Medarex Inc	Anticuerpos humanos que se enlazan a cd70 y usos de los mismos.
TWI412367B (zh)	2006-12-28	2013-10-21	梅達雷克斯有限責任公司	化學鏈接劑與可裂解基質以及其之綴合物
US9090693B2 (en)	2007-01-25	2015-07-28	Dana-Farber Cancer Institute	Use of anti-EGFR antibodies in treatment of EGFR mutant mediated disease
AR065404A1 (es)	2007-02-21	2009-06-03	Medarex Inc	Conjugados farmaco-ligando, los que se unen a citotoxinas potentes, composicion farmaceutica que los contienen y su uso para retardar o detener el crecimiento de un tumor en un mamifero
CA2680854C (en) *	2007-03-15	2017-02-14	Ludwig Institute For Cancer Research	Treatment method using egfr antibodies and src inhibitors and related formulations
US9901567B2 (en)	2007-08-01	2018-02-27	Syntarga B.V.	Substituted CC-1065 analogs and their conjugates
CN108424454B (zh)	2007-08-14	2022-05-31	路德维格癌症研究所有限公司	靶向egf受体的单克隆抗体175及其衍生物和用途
ES2441115T3 (es) *	2007-11-13	2014-01-31	The Scripps Research Institute	Derivados de CBI sujetos a activación reductora
ES2647317T3 (es)	2008-11-03	2017-12-20	Syntarga B.V.	Análogos de CC-1065 y sus conjugados
CN102341412B (zh)	2009-03-05	2018-01-05	梅达雷克斯有限责任公司	特异于cadm1 的全人抗体
DK2421898T3 (en)	2009-04-20	2016-05-30	Oxford Biotherapeutics Ltd	Cadherin-17 SPECIFIC ANTIBODIES
US20110076232A1 (en) *	2009-09-29	2011-03-31	Ludwig Institute For Cancer Research	Specific binding proteins and uses thereof
EP2470569A1 (en)	2009-10-13	2012-07-04	Oxford Biotherapeutics Ltd.	Antibodies against epha10
DE102009051438A1 (de)	2009-10-30	2011-05-05	Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts	Fluoreszenzfarbstoffe
PT3056203T (pt)	2010-04-21	2018-02-15	Syntarga Bv	Conjugados de análogos de cc-1065 e ligantes bifuncionais
WO2012171020A1 (en)	2011-06-10	2012-12-13	Mersana Therapeutics, Inc.	Protein-polymer-drug conjugates
PL2726508T3 (pl)	2011-06-28	2017-12-29	Oxford Biotherapeutics Ltd	Przeciwciała przeciwko cyklazie ADP-rybozylowej 2
CA2891280C (en)	2012-11-24	2018-03-20	Hangzhou Dac Biotech Co., Ltd.	Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
CA2892863C (en)	2012-12-10	2022-03-15	Mersana Therapeutics, Inc.	Polymeric scaffold based on phf for targeted drug delivery
WO2014093640A1 (en)	2012-12-12	2014-06-19	Mersana Therapeutics,Inc.	Hydroxy-polmer-drug-protein conjugates
US9089614B2 (en)	2012-12-21	2015-07-28	Bioalliance C.V.	Hydrophilic self-immolative linkers and conjugates thereof
PT2978760T (pt) *	2013-03-28	2019-05-31	Scripps Research Inst	Derivado n-acilo o-amino fenol cbi cíclico
WO2015050959A1 (en)	2013-10-01	2015-04-09	Yale University	Anti-kit antibodies and methods of use thereof
KR102087850B1 (ko)	2013-10-11	2020-03-12	메르사나 테라퓨틱스, 인코포레이티드	단백질-고분자-약물 접합체
ES2754397T3 (es)	2013-10-11	2020-04-17	Asana Biosciences Llc	Conjugados de proteína-polímero-fármaco
RU2680404C2 (ru)	2014-01-10	2019-02-21	Синтон Байофармасьютикалс Б. В.	Способ очистки cys-связанных конъюгатов антитело-лекарственное средство
US10464955B2 (en)	2014-02-28	2019-11-05	Hangzhou Dac Biotech Co., Ltd.	Charged linkers and their uses for conjugation
CA2943228C (en)	2014-03-20	2023-03-14	Bristol-Myers Squibb Company	Stabilized fibronectin based scaffold molecules
US9950077B2 (en)	2014-06-20	2018-04-24	Bioalliance C.V.	Anti-folate receptor alpha (FRA) antibody-drug conjugates and methods of using thereof
AU2015349878A1 (en)	2014-11-21	2017-05-25	Bristol-Myers Squibb Company	Antibodies against CD73 and uses thereof
JP6668345B2 (ja)	2014-11-21	2020-03-18	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	修飾された重鎖定常領域を含む抗体
CA2969067A1 (en)	2014-11-25	2016-06-02	Bristol-Myers Squibb Company	Novel pd-l1 binding polypeptides for imaging
JP2018510864A (ja)	2015-03-10	2018-04-19	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	トランスグルタミナーゼによって結合可能な抗体およびそれによって製造される結合体
DK3303396T5 (da)	2015-05-29	2024-10-07	Bristol Myers Squibb Co	Antistoffer mod ox40 og anvendelser deraf
NZ739830A (en)	2015-07-12	2021-12-24	Hangzhou Dac Biotech Co Ltd	Bridge linkers for conjugation of cell-binding molecules
US9839687B2 (en)	2015-07-15	2017-12-12	Suzhou M-Conj Biotech Co., Ltd.	Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
CN104961645A (zh) *	2015-07-22	2015-10-07	中国药科大学	苯氧乙酸类衍生物、其制备方法及其作为药物的用途
CA3008678A1 (en)	2015-12-21	2017-06-29	Bristol-Myers Squibb Company	Variant antibodies for site-specific conjugation
IL260289B (en)	2016-01-08	2022-08-01	Bioalliance Cv	Tetravalent anti-psgl-1 antibodies and uses thereof
EP3423494A1 (en)	2016-03-04	2019-01-09	Bristol-Myers Squibb Company	Combination therapy with anti-cd73 antibodies
WO2018004338A1 (en)	2016-06-27	2018-01-04	Tagworks Pharmaceuticals B.V.	Cleavable tetrazine used in bio-orthogonal drug activation
CN109641911B (zh)	2016-08-19	2023-02-21	百时美施贵宝公司	seco-环丙吡咯并吲哚化合物和其抗体-药物缀合物以及制备和使用方法
US20190218294A1 (en)	2016-09-09	2019-07-18	Bristol-Myers Squibb Company	Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment
KR20220150408A (ko)	2016-11-14	2022-11-10	항저우 디에이씨 바이오테크 씨오, 엘티디	결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용
US11135307B2 (en)	2016-11-23	2021-10-05	Mersana Therapeutics, Inc.	Peptide-containing linkers for antibody-drug conjugates
US20200299400A1 (en)	2017-05-25	2020-09-24	Bristol-Myers Squibb Company	Antibodies comprising modified heavy constant regions
AU2018290330A1 (en)	2017-06-22	2020-01-02	Mersana Therapeutics, Inc.	Methods of producing drug-carrying polymer scaffolds and protein-polymer-drug conjugates
AU2019262520B2 (en)	2018-05-04	2025-07-10	Tagworks Pharmaceuticals B.V.	Tetrazines for high click conjugation yield in vivo and high click release yield
CA3099421C (en)	2018-05-04	2025-05-06	Tagworks Pharmaceuticals B.V.	COMPOUNDS INCLUDING A BINDER TO INCREASE TRANSCYCLOOCTENE STABILITY
CN113365664A (zh)	2018-10-29	2021-09-07	梅尔莎纳医疗公司	具有含肽接头的半胱氨酸工程化的抗体-药物缀合物
IL289094A (en)	2019-06-17	2022-02-01	Tagworks Pharmaceuticals B V	Tetrazines for increasing the speed and yield of the "click release" reaction
DK3983363T3 (da)	2019-06-17	2024-06-24	Tagworks Pharmaceuticals B V	Forbindelser til hurtig og effektiv klikfrigivelse
US20250327057A1 (en)	2021-09-06	2025-10-23	Veraxa Biotech Gmbh	Novel aminoacyl-trna synthetase variants for genetic code expansion in eukaryotes
EP4426727A2 (en)	2021-11-03	2024-09-11	Hangzhou Dac Biotech Co., Ltd.	Specific conjugation of an antibody
DK4186529T3 (da)	2021-11-25	2025-08-25	Veraxa Biotech Gmbh	Forbedrede antistof-payload-konjugater (apc) fremstillet ved stedspecifik konjugering ved hjælp af genetisk kodeudvidelse
WO2023094525A1 (en)	2021-11-25	2023-06-01	Veraxa Biotech Gmbh	Improved antibody-payload conjugates (apcs) prepared by site-specific conjugation utilizing genetic code expansion
US20250135011A1 (en)	2021-12-08	2025-05-01	European Molecular Biology Laboratory	Hydrophilic tetrazine-functionalized payloads for preparation of targeting conjugates
US20250114489A1 (en)	2022-02-15	2025-04-10	Tagworks Pharmaceuticals B.V.	Masked il12 protein
CA3261603A1 (en)	2022-07-15	2024-01-18	Pheon Therapeutics Ltd	ANTIBODY-DRUG CONJUGATES
WO2024080872A1 (en)	2022-10-12	2024-04-18	Tagworks Pharmaceuticals B.V.	Strained bicyclononenes
WO2024153789A1 (en)	2023-01-20	2024-07-25	Basf Se	Stabilized biopolymer composition, their manufacture and use
WO2024191293A1 (en)	2023-03-10	2024-09-19	Tagworks Pharmaceuticals B.V.	Trans-cyclooctene with improved t-linker
KR20260046464A (ko)	2023-07-27	2026-04-07	베락사 바이오테크 게엠베하	친수성 트랜스-시클로옥텐(hyTCO) 화합물, 이를 포함하는 구조체 및 접합체
WO2025056807A1 (en)	2023-09-15	2025-03-20	Basf Se	Stabilized biopolymer composition, their manufacture and use
WO2025149667A1 (en)	2024-01-12	2025-07-17	Pheon Therapeutics Ltd	Antibody drug conjugates and uses thereof
WO2025174248A1 (en)	2024-02-16	2025-08-21	Tagworks Pharmaceuticals B.V.	Trans-cyclooctenes with "or gate" release
WO2026043376A1 (en)	2024-08-22	2026-02-26	Tagworks Pharmaceuticals B.V.	Trans-cyclooctene formulations
WO2026078060A1 (en)	2024-10-08	2026-04-16	Basf Se	Tocopherol alkoxylates for biopolymer stabilization

Family Cites Families (1)

* Cited by examiner, † Cited by third party
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

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
2003
- 2003-04-15 US US10/417,043 patent/US20040002528A1/en not_active Abandoned
2004
- 2004-06-24 US US10/876,992 patent/US20050032860A1/en not_active Abandoned

Also Published As

Publication number	Publication date
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
JPH11513391A (ja)	1999-11-16
US20040002528A1 (en)	2004-01-01
AU727608B2 (en)	2000-12-14

Legal Events

Date	Code	Title	Description
2003-10-31	RENW	Renewal (renewal fees accepted)
2006-10-27	RENW	Renewal (renewal fees accepted)

Publication	Publication Date	Title
NZ321172A (en)	2000-02-28	CBI analogs of CC-1065 and the duocarmycins
Boger et al.	1995	1, 2, 9, 9a-Tetrahydrocyclopropa [c] benz [e] indol-4-one (CBI) Analogs of CC-1065 and the Duocarmycins: Synthesis and Evaluation
Rawal et al.	1987	Photocyclization strategy for the synthesis of antitumor agent CC-1065: synthesis of dideoxy PDE-I and PDE-II. Synthesis of thiophene and furan analogs of dideoxy PDE-I and PDE-II
KR100295128B1 (ko)	2001-09-17	인돌로일구아니딘유도체
US6271251B1 (en)	2001-08-07	Substituted guanidine derivatives, process for production thereof, and pharmaceutical uses thereof
US5834493A (en)	1998-11-10	Indole derivatives as 5-HT1A and/or 5-HT2 ligands
JPH06507182A (ja)	1994-08-11	Ｎ−スルホニル−２−オキソインドール誘導体、それらの製造、及びそれらが存在する薬学的組成物
SK286568B6 (sk)	2009-01-07	Inhibítory farnezyl proteín transferázy
JP2001519412A (ja)	2001-10-23	Ｃｃ−１０６５およびデュオカルマイシンのイソ−ｃｂｉおよびイソ−ｃｉ類似体
FR2655988A1 (fr)	1991-06-21	Nouveaux derives de la napht-1-yl piperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
EA004805B1 (ru)	2004-08-26	5-аминоиндено [1, 2-c]пиразол-4-оны в качестве противораковых и антипролиферативных агентов
JP2004529887A (ja)	2004-09-30	腫瘍治療のためのプロドラッグとしてのピロロ−インドールおよびピロロ−キノリン誘導体
JP3563076B2 (ja)	2004-09-08	ピロロアゼピン誘導体
Mohamadi et al.	1994	Total synthesis and biological properties of novel antineoplastic (chloromethyl) furanoindolines: an asymmetric hydroboration mediated synthesis of the alkylation subunits
Boger et al.	1995	CBI-CDPBO1 and CBI-CDPBI1: CC-1065 analogs containing deep-seated modifications in the DNA binding subunit
JPWO1997020845A1 (ja)	1998-03-31	ピロロアゼピン誘導体
JPH0227358B2 (2)	1990-06-15
EP2185561A2 (fr)	2010-05-19	Dérivés de 1,2,3,4-tetrahydropyrroloý1,2-a¨pyrazine-6-carboxamides et de 2,3,4,5-tetrahydropyrroloý1,2-a¨ý1,4¨-diazépine-7-carboxamides, leur préparation et leur application en thérapeutique
HU219590B (hu)	2001-05-28	Eljárás hexahidrobenz[c,d]indol-származékok előállítására
KR20060085675A (ko)	2006-07-27	이상지혈증 치료를 위한 화합물 및 방법
JPH10237073A (ja)	1998-09-08	新規な置換グアニジン誘導体およびその製法
JP3162572B2 (ja)	2001-05-08	インドロイルグアニジン誘導体
CA2297279C (fr)	2004-05-18	Nouveaux composes cyano-indoles inhibiteurs de recapture de serotonine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
Boger et al.	1995	CC-1065 CBI analogs: an example of enhancement of DNA alkylation efficiency through introduction of stabilizing electrostatic interactions
CA2376876C (fr)	2006-07-11	Nouveaux derives d'isoindoloindolones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent