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
Links
- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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 |
|---|---|---|---|
| NZNZ536107 | 2004-10-22 | ||
| NZ536107A NZ536107A (en) | 2004-10-22 | 2004-10-22 | Nitrobenzindoles and their use in cancer therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2007118938A true RU2007118938A (ru) | 2008-11-27 |
Family
ID=36203204
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007118938/04A RU2007118938A (ru) | 2004-10-22 | 2005-10-21 | Нитробензиндолы и их применение в терапии рака |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7718688B2 (enExample) |
| EP (1) | EP1809603A4 (enExample) |
| JP (1) | JP2008517905A (enExample) |
| KR (1) | KR20070083806A (enExample) |
| CN (1) | CN101044114B (enExample) |
| AU (1) | AU2005296389B2 (enExample) |
| BR (1) | BRPI0517285A (enExample) |
| CA (1) | CA2584702A1 (enExample) |
| IL (1) | IL182652A0 (enExample) |
| MX (1) | MX2007004596A (enExample) |
| NZ (1) | NZ536107A (enExample) |
| RU (1) | RU2007118938A (enExample) |
| WO (1) | WO2006043839A1 (enExample) |
| ZA (1) | ZA200703699B (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5346589B2 (ja) * | 2006-02-02 | 2013-11-20 | シンタルガ・ビーブイ | 水溶性ｃｃ−１０６５類似体及びその接合体 |
| 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 |
| HUE025137T2 (en) | 2007-08-21 | 2016-01-28 | Senomyx Inc | Compositions are bitter taste blocking (blocking) compounds |
| NZ571028A (en) * | 2008-09-03 | 2011-01-28 | Auckland Uniservices Ltd | Nitrobenzindole compounds and their use in cancer treatment |
| HUE035798T2 (en) | 2008-11-03 | 2018-05-28 | Syntarga Bv | CC-1065 analogues and conjugates |
| HUE030846T2 (en) | 2010-04-21 | 2017-06-28 | Syntarga Bv | 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 |
| US9278124B2 (en) | 2012-10-16 | 2016-03-08 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| EP2948184B1 (en) | 2014-01-10 | 2016-03-23 | Synthon Biopharmaceuticals B.V. | Duocarmycin adcs showing improved in vivo antitumor activity |
| RU2686085C2 (ru) | 2014-01-10 | 2019-04-24 | Синтон Байофармасьютикалс Б. В. | Конъюгаты антитело-лекарственное средство (adc) с дуокармицином, применяемые для лечения рака эндометрия |
| LT3092010T (lt) | 2014-01-10 | 2018-10-25 | Synthon Biopharmaceuticals B.V. | Metodas, skirtas gryninimui cys-sujungtų antikūno-vaisto konjugatų |
| DK3160513T3 (da) | 2014-06-30 | 2020-04-06 | Glykos Finland Oy | Saccharidderivat af en toksisk payload og antistofkonjugater deraf |
| 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 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0938474B1 (en) * | 1996-09-12 | 2005-11-23 | Auckland Uniservices Limited | Cyclopropylindole compounds and their use as prodrugs |
| US7192977B2 (en) * | 2001-02-22 | 2007-03-20 | School Of Pharmacy | Benz-indole and benzo-quinoline derivatives as prodrugs for tumor treatment |
| US7235578B2 (en) * | 2002-05-17 | 2007-06-26 | Auckland Uniservices Limited | Processes for preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl-(amine-derived)] compounds and analogues thereof, and to products obtained therefrom |
| 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 |
-
2004
- 2004-10-22 NZ NZ536107A patent/NZ536107A/en not_active IP Right Cessation
-
2005
- 2005-10-21 RU RU2007118938/04A patent/RU2007118938A/ru not_active Application Discontinuation
- 2005-10-21 WO PCT/NZ2005/000278 patent/WO2006043839A1/en not_active Ceased
- 2005-10-21 KR KR1020077009468A patent/KR20070083806A/ko not_active Ceased
- 2005-10-21 EP EP05800725A patent/EP1809603A4/en not_active Withdrawn
- 2005-10-21 JP JP2007537835A patent/JP2008517905A/ja active Pending
- 2005-10-21 US US11/666,014 patent/US7718688B2/en not_active Expired - Fee Related
- 2005-10-21 AU AU2005296389A patent/AU2005296389B2/en not_active Ceased
- 2005-10-21 CA CA002584702A patent/CA2584702A1/en not_active Abandoned
- 2005-10-21 BR BRPI0517285-3A patent/BRPI0517285A/pt not_active Application Discontinuation
- 2005-10-21 CN CN2005800362035A patent/CN101044114B/zh not_active Expired - Fee Related
- 2005-10-21 MX MX2007004596A patent/MX2007004596A/es not_active Application Discontinuation
-
2007
- 2007-04-18 IL IL182652A patent/IL182652A0/en unknown
- 2007-05-08 ZA ZA200703699A patent/ZA200703699B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2584702A1 (en) | 2006-04-27 |
| BRPI0517285A (pt) | 2008-10-07 |
| EP1809603A4 (en) | 2009-09-02 |
| AU2005296389B2 (en) | 2012-03-15 |
| ZA200703699B (en) | 2008-10-29 |
| US7718688B2 (en) | 2010-05-18 |
| WO2006043839A1 (en) | 2006-04-27 |
| MX2007004596A (es) | 2007-06-22 |
| AU2005296389A1 (en) | 2006-04-27 |
| KR20070083806A (ko) | 2007-08-24 |
| CN101044114B (zh) | 2012-02-15 |
| CN101044114A (zh) | 2007-09-26 |
| IL182652A0 (en) | 2007-07-24 |
| NZ536107A (en) | 2007-06-29 |
| US20080119442A1 (en) | 2008-05-22 |
| JP2008517905A (ja) | 2008-05-29 |
| EP1809603A1 (en) | 2007-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2007118938A (ru) | Нитробензиндолы и их применение в терапии рака | |
| EP2209375B1 (en) | Parp inhibitor compounds, compositions and methods of use | |
| KR20160132130A (ko) | 폐의 비소세포 암종 및 난소암을 치료하기 위한 디안하이드로갈락티톨 및 이의 유사체 또는 유도체 | |
| US12448388B2 (en) | PRMT5 inhibitors and uses thereof | |
| PL185737B1 (pl) | Nowe zastosowanie inhibitorów cGMP-fosfodiesterazy | |
| CN111565756A (zh) | 包含生物活性化合物的具有刚性间隔基团的聚合物 | |
| JP2017512841A5 (enExample) | ||
| ES3011282T3 (en) | Imidazo[4,5-c]pyridine derivatives as toll-like receptor agonsits | |
| KR20220008869A (ko) | 항암 핵 호르몬 수용체-표적화 화합물 | |
| JP2000510828A (ja) | 腫瘍崩壊剤および放射線療法の臨床効果を増強するためのプロテインキナーゼｃ阻害剤の使用 | |
| TW201722421A (zh) | 雙脫水半乳糖醇或其衍生物和類似物藉由ｄｎａ損傷之誘導和細胞周期之延宕治療非小細胞肺癌、神經膠母細胞瘤及卵巢癌之用途 | |
| US20170056336A1 (en) | Co-targeting androgen receptor splice variants and mtor signaling pathway for the treatment of castration-resistant prostate cancer | |
| US20170015672A1 (en) | Substituted pyrrolo[2,3-d]pyrimidines for selectively targeting tumor cells with fr-alpha and fr-beta type receptors | |
| CN119161349A (zh) | 一类kras g12d蛋白降解剂及其用途 | |
| JP2008517905A5 (enExample) | ||
| CN101484443A (zh) | 放射线治疗增强剂 | |
| US20150126536A1 (en) | Methods of Using Selective Chemotherapeutic Agents for Targeting Tumor Cells | |
| US10561658B2 (en) | Thieno- and pyrrolopyrimidine analogues as anticancer agents and methods of use thereof | |
| CN101155600B (zh) | 放射线治疗增强剂 | |
| US20200147216A1 (en) | Disease detection and treatment through activation of compounds using external energy | |
| TW202108570A (zh) | 抗癌核荷爾蒙受體標靶化合物 | |
| CA2444334A1 (fr) | Associations pharmaceutiques a base de derives de pyridoindolone et d'agents anticancereux | |
| WO2014106763A1 (en) | Pyridopyrazines as anticancer agents | |
| HUP0402578A2 (hu) | 3-Heteroaril-3,5-dihidro-4-oxo-4H-piridazino[4,5-b]indol-1-karboxamid-származékok, előállításuk, intermedierjeik és a vegyületeket tartalmazó gyógyászati készítmények | |
| US20250122208A1 (en) | Chemokine receptor modulators and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA93 | Acknowledgement of application withdrawn (no request for examination) |
Effective date: 20090206 |