NZ321172A - CBI analogs of CC-1065 and the duocarmycins - Google Patents
CBI analogs of CC-1065 and the duocarmycinsInfo
- Publication number
- NZ321172A NZ321172A NZ321172A NZ32117296A NZ321172A NZ 321172 A NZ321172 A NZ 321172A NZ 321172 A NZ321172 A NZ 321172A NZ 32117296 A NZ32117296 A NZ 32117296A NZ 321172 A NZ321172 A NZ 321172A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- group
- pyrrolidine ring
- substituted pyrrolidine
- hydrogen
- Prior art date
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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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)
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 (enExample) |
| EP (1) | EP0862553A4 (enExample) |
| JP (1) | JPH11513391A (enExample) |
| AU (1) | AU727608B2 (enExample) |
| CA (1) | CA2233936A1 (enExample) |
| NZ (1) | NZ321172A (enExample) |
| WO (1) | WO1997012862A1 (enExample) |
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| 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 |
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| CN120569216A (zh) | 2023-01-20 | 2025-08-29 | 巴斯夫欧洲公司 | 稳定型生物聚合物组合物、其制造和用途 |
| JP2026509291A (ja) | 2023-03-10 | 2026-03-17 | タグワークス ファーマシューティカルス ビー．ブイ． | 向上されたｔ－リンカーを有するトランス－シクロオクテン |
| EP4750750A1 (en) | 2023-07-27 | 2026-06-03 | Veraxa Biotech GmbH | Hydrophilic trans-cyclooctene (hytco) compounds, constructs and conjugates containing the same |
| CN122206462A (zh) | 2023-09-15 | 2026-06-12 | 巴斯夫欧洲公司 | 稳定型生物聚合物组合物、其制造和用途 |
| 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 |
| TW202617187A (zh) | 2024-08-22 | 2026-05-01 | 荷蘭商泰格沃克斯製藥有限公司 | 反-環辛烯調配物 |
| WO2026078060A1 (en) | 2024-10-08 | 2026-04-16 | Basf Se | Tocopherol alkoxylates for biopolymer stabilization |
| WO2026139575A1 (en) | 2024-12-23 | 2026-07-02 | Veraxa Biotech Gmbh | Novel tco-functionalized glycan engineered immunoglobulin molecules, novel tco-functionalized saccharide compounds for preparing the same, and novel antibody payload conjugates |
Family Cites Families (1)
| 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 JP JP9514522A patent/JPH11513391A/ja not_active Abandoned
- 1996-10-03 EP EP96936498A patent/EP0862553A4/en not_active Withdrawn
- 1996-10-03 AU AU74315/96A patent/AU727608B2/en not_active Ceased
- 1996-10-03 CA CA002233936A patent/CA2233936A1/en not_active Abandoned
- 1996-10-03 US US09/051,264 patent/US6548530B1/en not_active Expired - Fee Related
- 1996-10-03 WO PCT/US1996/016481 patent/WO1997012862A1/en not_active Ceased
- 1996-10-03 NZ NZ321172A patent/NZ321172A/en unknown
-
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 |
|---|---|
| AU7431596A (en) | 1997-04-28 |
| US6548530B1 (en) | 2003-04-15 |
| JPH11513391A (ja) | 1999-11-16 |
| AU727608B2 (en) | 2000-12-14 |
| US20040002528A1 (en) | 2004-01-01 |
| WO1997012862A1 (en) | 1997-04-10 |
| EP0862553A4 (en) | 1999-02-03 |
| US20050032860A1 (en) | 2005-02-10 |
| CA2233936A1 (en) | 1997-04-10 |
| EP0862553A1 (en) | 1998-09-09 |
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