RU2007118938A - Нитробензиндолы и их применение в терапии рака - Google Patents
Нитробензиндолы и их применение в терапии рака Download PDFInfo
- Publication number
- RU2007118938A RU2007118938A RU2007118938/04A RU2007118938A RU2007118938A RU 2007118938 A RU2007118938 A RU 2007118938A RU 2007118938/04 A RU2007118938/04 A RU 2007118938/04A RU 2007118938 A RU2007118938 A RU 2007118938A RU 2007118938 A RU2007118938 A RU 2007118938A
- Authority
- RU
- Russia
- Prior art keywords
- indole
- chloromethyl
- benzo
- dihydro
- carbonyl
- Prior art date
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- 238000011275 oncology therapy Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 31
- 238000000034 method Methods 0.000 claims 17
- 125000003277 amino group Chemical group 0.000 claims 16
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 12
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 8
- 150000002367 halogens Chemical class 0.000 claims 8
- 210000004881 tumor cell Anatomy 0.000 claims 8
- 229910019142 PO4 Inorganic materials 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000010452 phosphate Substances 0.000 claims 6
- -1 NR 2 2 Inorganic materials 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 206010021143 Hypoxia Diseases 0.000 claims 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 4
- 230000001146 hypoxic effect Effects 0.000 claims 4
- 208000020816 lung neoplasm Diseases 0.000 claims 4
- 208000037841 lung tumor Diseases 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 238000011084 recovery Methods 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 102000004459 Nitroreductase Human genes 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims 3
- 108020001162 nitroreductase Proteins 0.000 claims 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims 2
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 210000000481 breast Anatomy 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 2
- 230000026030 halogenation Effects 0.000 claims 2
- 238000005658 halogenation reaction Methods 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 238000006396 nitration reaction Methods 0.000 claims 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 2
- 238000007363 ring formation reaction Methods 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 2
- UOORRWUZONOOLO-OWOJBTEDSA-N (E)-1,3-dichloropropene Chemical compound ClC\C=C\Cl UOORRWUZONOOLO-OWOJBTEDSA-N 0.000 claims 1
- LATMWQAFEIWYRQ-XVNBXDOJSA-N 1-(chloromethyl)-3-[(e)-3-(3-hydroxy-4-methoxyphenyl)prop-2-enoyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C(O)C(OC)=CC=C1\C=C\C(=O)N1C(C=C([N+]([O-])=O)C=2C3=CC=C(C=2)S(N)(=O)=O)=C3C(CCl)C1 LATMWQAFEIWYRQ-XVNBXDOJSA-N 0.000 claims 1
- JNCZLHZYZFUYPG-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-(2-hydroxyethoxy)-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound OCCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)S(=O)(=O)N)=CC2=C1 JNCZLHZYZFUYPG-UHFFFAOYSA-N 0.000 claims 1
- ONBRUSLZBBCEOY-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-6-carbonitrile Chemical compound C1=C([N+]([O-])=O)C2=C(C#N)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 ONBRUSLZBBCEOY-UHFFFAOYSA-N 0.000 claims 1
- QSJBKCXFDLMTHS-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-6-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=C(C(N)=O)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 QSJBKCXFDLMTHS-UHFFFAOYSA-N 0.000 claims 1
- CSTIBFCQKXQVDK-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-6-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=C(S(N)(=O)=O)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 CSTIBFCQKXQVDK-UHFFFAOYSA-N 0.000 claims 1
- DKJMAWIEBGBFPH-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-carbonitrile Chemical compound C1=C([N+]([O-])=O)C2=CC(C#N)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 DKJMAWIEBGBFPH-UHFFFAOYSA-N 0.000 claims 1
- AGRPHKIPGKQQIF-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC(C(N)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 AGRPHKIPGKQQIF-UHFFFAOYSA-N 0.000 claims 1
- HYBNOGLMWRFIKT-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC(S(N)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 HYBNOGLMWRFIKT-UHFFFAOYSA-N 0.000 claims 1
- GOQCLYGXSWDFNL-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonohydrazide Chemical compound C1=C([N+]([O-])=O)C2=CC(S(=O)(=O)NN)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 GOQCLYGXSWDFNL-UHFFFAOYSA-N 0.000 claims 1
- BPQAYFOOHPWBLW-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-8-carbonitrile Chemical compound C1=C([N+]([O-])=O)C2=CC=C(C#N)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 BPQAYFOOHPWBLW-UHFFFAOYSA-N 0.000 claims 1
- VMJMFHABPZZZRC-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-8-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC=C(C(N)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 VMJMFHABPZZZRC-UHFFFAOYSA-N 0.000 claims 1
- PHYSKKPAAAGXEK-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-8-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC=C(S(N)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 PHYSKKPAAAGXEK-UHFFFAOYSA-N 0.000 claims 1
- FDAITWSCHGZWGT-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n,n-dimethyl-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC(S(=O)(=O)N(C)C)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 FDAITWSCHGZWGT-UHFFFAOYSA-N 0.000 claims 1
- LMXAPRZDOFHAGK-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-(2-hydroxyethyl)-5-nitro-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC(C(=O)NCCO)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 LMXAPRZDOFHAGK-UHFFFAOYSA-N 0.000 claims 1
- KRUNPKDABQVLHA-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-(2-hydroxyethyl)-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC(S(=O)(=O)NCCO)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 KRUNPKDABQVLHA-UHFFFAOYSA-N 0.000 claims 1
- RNYIWIYMMHVWIU-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-[2-(dimethylamino)ethyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)S(=O)(=O)NCCN(C)C)=CC2=C1 RNYIWIYMMHVWIU-UHFFFAOYSA-N 0.000 claims 1
- UBJJRHQOKABVOI-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-hydroxy-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC(S(=O)(=O)NO)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 UBJJRHQOKABVOI-UHFFFAOYSA-N 0.000 claims 1
- MPBMMEDHTJHPJB-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-methyl-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)S(=O)(=O)NC)=CC2=C1 MPBMMEDHTJHPJB-UHFFFAOYSA-N 0.000 claims 1
- YOACZPGGGOMPDE-UHFFFAOYSA-N 1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC(C(N)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 YOACZPGGGOMPDE-UHFFFAOYSA-N 0.000 claims 1
- LAHZRRYNNDURLE-UHFFFAOYSA-N 1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-8-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC=C(S(N)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 LAHZRRYNNDURLE-UHFFFAOYSA-N 0.000 claims 1
- IEZAHBPNCWUCOQ-RUDMXATFSA-N 1-(chloromethyl)-n-(2-hydroxyethyl)-3-[(e)-3-(4-methoxyphenyl)prop-2-enoyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)N1C(C=C([N+]([O-])=O)C=2C3=CC=C(C=2)C(=O)NCCO)=C3C(CCl)C1 IEZAHBPNCWUCOQ-RUDMXATFSA-N 0.000 claims 1
- GFGCVLXZJQENDB-RUDMXATFSA-N 1-(chloromethyl)-n-(2-hydroxyethyl)-3-[(e)-3-(4-methoxyphenyl)prop-2-enoyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)N1C(C=C([N+]([O-])=O)C=2C3=CC=C(C=2)S(=O)(=O)NCCO)=C3C(CCl)C1 GFGCVLXZJQENDB-RUDMXATFSA-N 0.000 claims 1
- POALEYSRWKHSKO-UHFFFAOYSA-N 1-(chloromethyl)-n-(2-hydroxyethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC(C(=O)NCCO)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 POALEYSRWKHSKO-UHFFFAOYSA-N 0.000 claims 1
- RJLBITIFTMTFDJ-UHFFFAOYSA-N 1-(chloromethyl)-n-(2-hydroxyethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC(S(=O)(=O)NCCO)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 RJLBITIFTMTFDJ-UHFFFAOYSA-N 0.000 claims 1
- VQMQJTIXPZZTHY-UHFFFAOYSA-N 1-(chloromethyl)-n-[2-(dimethylamino)ethyl]-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC(C(=O)NCCN(C)C)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 VQMQJTIXPZZTHY-UHFFFAOYSA-N 0.000 claims 1
- ANMNEGCPBPTGMK-UHFFFAOYSA-N 1-(chloromethyl)-n-[2-(dimethylamino)ethyl]-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-8-carboxamide Chemical compound C1=C([N+]([O-])=O)C2=CC=C(C(=O)NCCN(C)C)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 ANMNEGCPBPTGMK-UHFFFAOYSA-N 0.000 claims 1
- SMSGKARSVYZHOQ-UHFFFAOYSA-N 1-[1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indol-6-yl]ethanone Chemical compound C1=C([N+]([O-])=O)C2=C(C(C)=O)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 SMSGKARSVYZHOQ-UHFFFAOYSA-N 0.000 claims 1
- VOKGXYWYOIEEEQ-UHFFFAOYSA-N 1-[1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indol-7-yl]ethanone Chemical compound C1=C([N+]([O-])=O)C2=CC(C(C)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 VOKGXYWYOIEEEQ-UHFFFAOYSA-N 0.000 claims 1
- HBUGUFVSORQDFD-UHFFFAOYSA-N 1-[1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indol-8-yl]ethanone Chemical compound C1=C([N+]([O-])=O)C2=CC=C(C(C)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 HBUGUFVSORQDFD-UHFFFAOYSA-N 0.000 claims 1
- XDWNQMVXLIYVJG-UHFFFAOYSA-N 1-[1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indol-6-yl]ethanone Chemical compound C1=C([N+]([O-])=O)C2=C(C(C)=O)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 XDWNQMVXLIYVJG-UHFFFAOYSA-N 0.000 claims 1
- XTARRYIOOJBKAR-UHFFFAOYSA-N 1-[1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indol-7-yl]ethanone Chemical compound C1=C([N+]([O-])=O)C2=CC(C(C)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 XTARRYIOOJBKAR-UHFFFAOYSA-N 0.000 claims 1
- OCWVMULXKFFKLQ-UHFFFAOYSA-N 1-[5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-1,2-dihydrobenzo[e]indol-7-yl]ethanone Chemical compound C1=C(N)C2=CC(C(C)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 OCWVMULXKFFKLQ-UHFFFAOYSA-N 0.000 claims 1
- REBLBXCYDPNMFU-UHFFFAOYSA-N 5-amino-1-(chloromethyl)-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C(N)C2=CC(S(N)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 REBLBXCYDPNMFU-UHFFFAOYSA-N 0.000 claims 1
- HXTOCPLOGIPMSZ-UHFFFAOYSA-N 5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-1,2-dihydrobenzo[e]indole-7-carbonitrile Chemical compound C1=C(N)C2=CC(C#N)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 HXTOCPLOGIPMSZ-UHFFFAOYSA-N 0.000 claims 1
- FCANZPUAMYFRBM-UHFFFAOYSA-N 5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-1,2-dihydrobenzo[e]indole-7-carboxamide Chemical compound C1=C(N)C2=CC(C(N)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 FCANZPUAMYFRBM-UHFFFAOYSA-N 0.000 claims 1
- AISKAQWMIIWMLK-UHFFFAOYSA-N 5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C(N)C2=CC(S(N)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 AISKAQWMIIWMLK-UHFFFAOYSA-N 0.000 claims 1
- XLBDPRIHVOLENG-UHFFFAOYSA-N 5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-(2-hydroxyethyl)-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound C1=C(N)C2=CC(S(=O)(=O)NCCO)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 XLBDPRIHVOLENG-UHFFFAOYSA-N 0.000 claims 1
- JUOUEFUFBKCDTN-UHFFFAOYSA-N 5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-n-methyl-1,2-dihydrobenzo[e]indole-7-sulfonamide Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C(N)=CC=43)S(=O)(=O)NC)=CC2=C1 JUOUEFUFBKCDTN-UHFFFAOYSA-N 0.000 claims 1
- 108010006654 Bleomycin Proteins 0.000 claims 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 1
- 239000012624 DNA alkylating agent Substances 0.000 claims 1
- 241000588724 Escherichia coli Species 0.000 claims 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims 1
- WXZOMBNPDJUSJP-UHFFFAOYSA-N [1-(chloromethyl)-5,6-dinitro-1,2-dihydrobenzo[e]indol-3-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1=C([N+]([O-])=O)C2=C([N+]([O-])=O)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 WXZOMBNPDJUSJP-UHFFFAOYSA-N 0.000 claims 1
- CWJXZICDUNWYNT-UHFFFAOYSA-N [1-(chloromethyl)-5,6-dinitro-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C([N+]([O-])=O)C2=C([N+]([O-])=O)C=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 CWJXZICDUNWYNT-UHFFFAOYSA-N 0.000 claims 1
- IGEXYFMZPKZJQH-UHFFFAOYSA-N [1-(chloromethyl)-5,7-dinitro-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C([N+]([O-])=O)C2=CC([N+]([O-])=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 IGEXYFMZPKZJQH-UHFFFAOYSA-N 0.000 claims 1
- HAPJQPJEQBJFGB-UHFFFAOYSA-N [1-(chloromethyl)-5,7-dinitro-2,3-dihydrobenzo[e]indol-1-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1NC2=CC([N+]([O-])=O)=C3C=C([N+]([O-])=O)C=CC3=C2C1(CCl)C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 HAPJQPJEQBJFGB-UHFFFAOYSA-N 0.000 claims 1
- CUUJCKOKECFPPI-UHFFFAOYSA-N [1-(chloromethyl)-5,9-dinitro-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C([N+]([O-])=O)C2=CC=CC([N+]([O-])=O)=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 CUUJCKOKECFPPI-UHFFFAOYSA-N 0.000 claims 1
- VABOGHWYNKJERS-UHFFFAOYSA-N [1-(chloromethyl)-5,9-dinitro-2,3-dihydrobenzo[e]indol-1-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1NC2=CC([N+]([O-])=O)=C3C=CC=C([N+]([O-])=O)C3=C2C1(CCl)C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 VABOGHWYNKJERS-UHFFFAOYSA-N 0.000 claims 1
- AOBBYGQDEDVVJT-UHFFFAOYSA-N [1-(chloromethyl)-7-methylsulfonyl-5-nitro-1,2-dihydrobenzo[e]indol-3-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1=C([N+]([O-])=O)C2=CC(S(C)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 AOBBYGQDEDVVJT-UHFFFAOYSA-N 0.000 claims 1
- DABBZWMVDTVEBN-UHFFFAOYSA-N [1-(chloromethyl)-7-methylsulfonyl-5-nitro-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C([N+]([O-])=O)C2=CC(S(C)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 DABBZWMVDTVEBN-UHFFFAOYSA-N 0.000 claims 1
- YHSMOBOHRHLNCV-UHFFFAOYSA-N [1-(chloromethyl)-8-methylsulfonyl-5-nitro-1,2-dihydrobenzo[e]indol-3-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1=C([N+]([O-])=O)C2=CC=C(S(C)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 YHSMOBOHRHLNCV-UHFFFAOYSA-N 0.000 claims 1
- CNKSSIIIWWYHBN-UHFFFAOYSA-N [1-(chloromethyl)-8-methylsulfonyl-5-nitro-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C([N+]([O-])=O)C2=CC=C(S(C)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 CNKSSIIIWWYHBN-UHFFFAOYSA-N 0.000 claims 1
- JNEFRXUIQUVTEG-UHFFFAOYSA-N [5-amino-1-(chloromethyl)-7-methylsulfonyl-1,2-dihydrobenzo[e]indol-3-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1=C(N)C2=CC(S(C)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 JNEFRXUIQUVTEG-UHFFFAOYSA-N 0.000 claims 1
- QLYIVYWIMWHWRQ-UHFFFAOYSA-N [5-amino-1-(chloromethyl)-7-methylsulfonyl-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C(N)C2=CC(S(C)(=O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 QLYIVYWIMWHWRQ-UHFFFAOYSA-N 0.000 claims 1
- WUVSAGBRTWDSPK-UHFFFAOYSA-N [5-amino-1-(chloromethyl)-8-methylsulfonyl-1,2-dihydrobenzo[e]indol-3-yl]-(5,6,7-trimethoxy-1h-indol-2-yl)methanone Chemical compound C1=C(N)C2=CC=C(S(C)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 WUVSAGBRTWDSPK-UHFFFAOYSA-N 0.000 claims 1
- ITWQEVQRPXKWDA-UHFFFAOYSA-N [5-amino-1-(chloromethyl)-8-methylsulfonyl-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C(N)C2=CC=C(S(C)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 ITWQEVQRPXKWDA-UHFFFAOYSA-N 0.000 claims 1
- ZNYKOZRGVWSEGR-UHFFFAOYSA-N [7-amino-1-(chloromethyl)-5-nitro-1,2-dihydrobenzo[e]indol-3-yl]-[5-[2-(dimethylamino)ethoxy]-1h-indol-2-yl]methanone Chemical compound C1=C([N+]([O-])=O)C2=CC(N)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 ZNYKOZRGVWSEGR-UHFFFAOYSA-N 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 claims 1
- 229960001561 bleomycin Drugs 0.000 claims 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 1
- 229960004316 cisplatin Drugs 0.000 claims 1
- 229960004397 cyclophosphamide Drugs 0.000 claims 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims 1
- 229960004679 doxorubicin Drugs 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229960005277 gemcitabine Drugs 0.000 claims 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
- 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 claims 1
- 230000002140 halogenating effect Effects 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 239000003999 initiator Substances 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 210000000936 intestine Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000004060 metabolic process Effects 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- RDHFVPXFTWSRDZ-UHFFFAOYSA-N methyl 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-carboxylate Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)C(=O)OC)=CC2=C1 RDHFVPXFTWSRDZ-UHFFFAOYSA-N 0.000 claims 1
- VXTWJWWWFAYIDU-UHFFFAOYSA-N methyl 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indole-8-carboxylate Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3C=4C=C(C5=CC=C(C=C5C=4C(CCl)C3)C(=O)OC)[N+]([O-])=O)=CC2=C1 VXTWJWWWFAYIDU-UHFFFAOYSA-N 0.000 claims 1
- HOQRMRAEBPDBKM-UHFFFAOYSA-N methyl 1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indole-7-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)C(=O)OC)=CC2=C1 HOQRMRAEBPDBKM-UHFFFAOYSA-N 0.000 claims 1
- FYEOKJDNSRSHEU-UHFFFAOYSA-N methyl 5-amino-1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-1,2-dihydrobenzo[e]indole-7-carboxylate Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C(N)=CC=43)C(=O)OC)=CC2=C1 FYEOKJDNSRSHEU-UHFFFAOYSA-N 0.000 claims 1
- 230000001035 methylating effect Effects 0.000 claims 1
- 229960001156 mitoxantrone Drugs 0.000 claims 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims 1
- CDYSYTQMAYGEHJ-UHFFFAOYSA-N n-[[1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5-nitro-1,2-dihydrobenzo[e]indol-7-yl]sulfonyl]propanamide Chemical compound CN(C)CCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)S(=O)(=O)NC(=O)CC)=CC2=C1 CDYSYTQMAYGEHJ-UHFFFAOYSA-N 0.000 claims 1
- 101150091037 nfsB gene Proteins 0.000 claims 1
- 230000000802 nitrating effect Effects 0.000 claims 1
- 229940127075 other antimetabolite Drugs 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229910052697 platinum Inorganic materials 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 229910000104 sodium hydride Inorganic materials 0.000 claims 1
- 239000012312 sodium hydride Substances 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
- UOORRWUZONOOLO-UHFFFAOYSA-N telone II Natural products ClCC=CCl UOORRWUZONOOLO-UHFFFAOYSA-N 0.000 claims 1
- 229960004964 temozolomide Drugs 0.000 claims 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- QVMPZNRFXAKISM-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=C2[N+]([O-])=NC(=N)N(O)C2=C1 QVMPZNRFXAKISM-UHFFFAOYSA-N 0.000 claims 1
- 229950002376 tirapazamine Drugs 0.000 claims 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 claims 1
- LHJZSWVADJCBNI-ONEGZZNKSA-N C/C=C/c(cc1O)ccc1OC Chemical compound C/C=C/c(cc1O)ccc1OC LHJZSWVADJCBNI-ONEGZZNKSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| NZNZ536107 | 2004-10-22 |
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| JP (1) | JP2008517905A (https=) |
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| CN (1) | CN101044114B (https=) |
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| EP1994000B1 (en) * | 2006-02-02 | 2017-08-23 | Syntarga B.V. | Water-soluble cc-1065 analogs and their conjugates |
| US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| US8076491B2 (en) | 2007-08-21 | 2011-12-13 | Senomyx, Inc. | Compounds that inhibit (block) bitter taste in composition and use thereof |
| KR101558193B1 (ko) | 2007-08-21 | 2015-10-12 | 세노믹스, 인코포레이티드 | 인간 ｔ2ｒ 쓴맛 수용체 및 이의 용도 |
| NZ571028A (en) * | 2008-09-03 | 2011-01-28 | Auckland Uniservices Ltd | Nitrobenzindole compounds and their use in cancer treatment |
| AU2009320481C1 (en) | 2008-11-03 | 2016-12-08 | Syntarga B.V. | Novel CC-1065 analogs and their conjugates |
| AU2011243294C1 (en) | 2010-04-21 | 2015-12-03 | Syntarga B.V. | Novel conjugates of CC-1065 analogs and bifunctional linkers |
| CN102827061A (zh) * | 2012-09-19 | 2012-12-19 | 兰州大学 | 5,6,7-三甲氧基吲哚类衍生物、制备方法及用途 |
| WO2014062856A1 (en) | 2012-10-16 | 2014-04-24 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| AU2015205574B2 (en) | 2014-01-10 | 2019-08-15 | Byondis B.V. | Method for purifying Cys-linked antibody-drug conjugates |
| HUE029672T2 (en) | 2014-01-10 | 2017-03-28 | Synthon Biopharmaceuticals Bv | Duokarmicin-ADCs for use in the treatment of endometrial cancer |
| CN105899236B (zh) | 2014-01-10 | 2019-07-26 | 斯索恩生物制药有限公司 | 表现出改进的体内抗肿瘤活性的倍癌霉素adc |
| EP3160513B1 (en) | 2014-06-30 | 2020-02-12 | Glykos Finland Oy | Saccharide derivative of a toxic payload and antibody conjugates thereof |
| JPWO2019004413A1 (ja) * | 2017-06-30 | 2020-05-07 | 東レ株式会社 | インドリン誘導体及びそれを含む細胞毒性剤 |
| CN112724068A (zh) * | 2020-12-30 | 2021-04-30 | 蔡桂坡 | 具有hdac抑制活性的吲哚类衍生物的合成方法及肿瘤应用 |
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| NZ334344A (en) | 1996-09-12 | 2000-08-25 | Cancer Res Campaign Tech | benzo[e]indole and pyrrolo[3,2-e]indole compounds and their use as prodrugs |
| JP4862120B2 (ja) * | 2001-02-22 | 2012-01-25 | ユニヴァーシティ オブ ブラッドフォード | 腫瘍治療のためのプロドラッグとしてのベンズ−インドールおよびベンゾ−キノリン誘導体 |
| WO2003097635A1 (en) * | 2002-05-17 | 2003-11-27 | Auckland Uniservices Limited | Processes for preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3h-[ring fused indol-5-yl(amine-derived)] compounds and analogues thereof, and to products obtained therefrom |
| NZ529249A (en) | 2003-10-31 | 2006-04-28 | Auckland Uniservices Ltd | Novel nitrophenyl mustard and nitrophenylaziridine alcohols and their corresponding phosphates and their use as targeted cytotoxic |
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2004
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2005
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- 2005-10-21 CA CA002584702A patent/CA2584702A1/en not_active Abandoned
- 2005-10-21 US US11/666,014 patent/US7718688B2/en not_active Expired - Fee Related
- 2005-10-21 BR BRPI0517285-3A patent/BRPI0517285A/pt not_active Application Discontinuation
- 2005-10-21 AU AU2005296389A patent/AU2005296389B2/en not_active Ceased
- 2005-10-21 WO PCT/NZ2005/000278 patent/WO2006043839A1/en not_active Ceased
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- 2005-10-21 RU RU2007118938/04A patent/RU2007118938A/ru not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| NZ536107A (en) | 2007-06-29 |
| US7718688B2 (en) | 2010-05-18 |
| US20080119442A1 (en) | 2008-05-22 |
| BRPI0517285A (pt) | 2008-10-07 |
| EP1809603A1 (en) | 2007-07-25 |
| JP2008517905A (ja) | 2008-05-29 |
| CN101044114B (zh) | 2012-02-15 |
| CN101044114A (zh) | 2007-09-26 |
| CA2584702A1 (en) | 2006-04-27 |
| AU2005296389A1 (en) | 2006-04-27 |
| AU2005296389B2 (en) | 2012-03-15 |
| EP1809603A4 (en) | 2009-09-02 |
| WO2006043839A1 (en) | 2006-04-27 |
| IL182652A0 (en) | 2007-07-24 |
| KR20070083806A (ko) | 2007-08-24 |
| MX2007004596A (es) | 2007-06-22 |
| ZA200703699B (en) | 2008-10-29 |
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