AU2005296389B2 - Nitrobenzindoles and their use in cancer therapy - Google Patents

Info

Publication number

AU2005296389B2

AU2005296389B2 AU2005296389A AU2005296389A AU2005296389B2 AU 2005296389 B2 AU2005296389 B2 AU 2005296389B2 AU 2005296389 A AU2005296389 A AU 2005296389A AU 2005296389 A AU2005296389 A AU 2005296389A AU 2005296389 B2 AU2005296389 B2 AU 2005296389B2

Authority

AU

Australia

Prior art keywords

benzo

dihydro

chloromethyl

indole

nitro

Prior art date

2004-10-22

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011275 oncology therapy Methods 0.000 title abstract description 8
• GNDINQYCDXTGEO-UHFFFAOYSA-N 2-nitro-1h-benzo[g]indole Chemical class C1=CC=CC2=C(NC([N+](=O)[O-])=C3)C3=CC=C21 GNDINQYCDXTGEO-UHFFFAOYSA-N 0.000 title description 3
• 206010021143 Hypoxia Diseases 0.000 claims abstract description 47
• 239000002246 antineoplastic agent Substances 0.000 claims abstract description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 211
• 239000007787 solid Substances 0.000 claims description 163
• 150000001875 compounds Chemical class 0.000 claims description 120
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 66
• 206010028980 Neoplasm Diseases 0.000 claims description 42
• 230000001146 hypoxic effect Effects 0.000 claims description 39
• 238000011282 treatment Methods 0.000 claims description 32
• 238000000034 method Methods 0.000 claims description 30
• -1 benzo[e]indole-7-carbonitrile Chemical compound 0.000 claims description 28
• 210000004027 cell Anatomy 0.000 claims description 27
• 229940124530 sulfonamide Drugs 0.000 claims description 26
• 125000003277 amino group Chemical group 0.000 claims description 20
• 201000011510 cancer Diseases 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 210000004881 tumor cell Anatomy 0.000 claims description 15
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 14
• 125000005605 benzo group Chemical group 0.000 claims description 14
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 13
• 229910019142 PO4 Inorganic materials 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 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 description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 239000010452 phosphate Substances 0.000 claims description 10
• 229910052727 yttrium Inorganic materials 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 9
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 9
• 229940127089 cytotoxic agent Drugs 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 7
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 7
• 208000037841 lung tumor Diseases 0.000 claims description 7
• 229910052721 tungsten Inorganic materials 0.000 claims description 7
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
• 238000001959 radiotherapy Methods 0.000 claims description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
• 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 description 4
• ZBTZUPULECIHOQ-UHFFFAOYSA-N C1=CC2=CC(C(=O)O)=CC=C2C2=C1NCC2 Chemical compound C1=CC2=CC(C(=O)O)=CC=C2C2=C1NCC2 ZBTZUPULECIHOQ-UHFFFAOYSA-N 0.000 claims description 4
• 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 description 4
• 239000002671 adjuvant Substances 0.000 claims description 4
• 210000000481 breast Anatomy 0.000 claims description 4
• 239000000872 buffer Substances 0.000 claims description 4
• 208000032839 leukemia Diseases 0.000 claims description 4
• 230000000802 nitrating effect Effects 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
• 239000003381 stabilizer Substances 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
• ALGIYXGLGIECNT-UHFFFAOYSA-N 3h-benzo[e]indole Chemical compound C1=CC=C2C(C=CN3)=C3C=CC2=C1 ALGIYXGLGIECNT-UHFFFAOYSA-N 0.000 claims description 3
• 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 3
• 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
• 125000000623 heterocyclic group Chemical group 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• PARCSDUIMULVIU-UHFFFAOYSA-N 1-propanoyl-2,3-dihydro-1H-benzo[e]indole-7-sulfonamide Chemical compound C(CC)(=O)C1CNC=2C=CC3=C(C1=2)C=CC(=C3)S(=O)(=O)N PARCSDUIMULVIU-UHFFFAOYSA-N 0.000 claims description 2
• 108010006654 Bleomycin Proteins 0.000 claims description 2
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
• 239000012624 DNA alkylating agent Substances 0.000 claims description 2
• 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 description 2
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
• 229930012538 Paclitaxel Natural products 0.000 claims description 2
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 229960001561 bleomycin Drugs 0.000 claims description 2
• 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 description 2
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 2
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 2
• 229940127093 camptothecin Drugs 0.000 claims description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
• 229960004316 cisplatin Drugs 0.000 claims description 2
• 229960004397 cyclophosphamide Drugs 0.000 claims description 2
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 2
• 229960003668 docetaxel Drugs 0.000 claims description 2
• 229960004679 doxorubicin Drugs 0.000 claims description 2
• 229960005277 gemcitabine Drugs 0.000 claims description 2
• 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 description 2
• 229960000485 methotrexate Drugs 0.000 claims description 2
• 230000001035 methylating effect Effects 0.000 claims description 2
• 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 description 2
• 229960001156 mitoxantrone Drugs 0.000 claims description 2
• 238000006396 nitration reaction Methods 0.000 claims description 2
• 229940127075 other antimetabolite Drugs 0.000 claims description 2
• 229960001592 paclitaxel Drugs 0.000 claims description 2
• 229910052697 platinum Inorganic materials 0.000 claims description 2
• 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 description 2
• 229960004964 temozolomide Drugs 0.000 claims description 2
• 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 2
• OZEDQORHGRJQAF-UHFFFAOYSA-N 1h-indole-7-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CC2=C1NC=C2 OZEDQORHGRJQAF-UHFFFAOYSA-N 0.000 claims 2
• KDFJMPAZFQVTCR-UHFFFAOYSA-N 2,3-dihydro-1h-benzo[e]indole Chemical compound C1=CC2=CC=CC=C2C2=C1NCC2 KDFJMPAZFQVTCR-UHFFFAOYSA-N 0.000 claims 2
• PXLRAEBBNSSDSC-UHFFFAOYSA-N 1-(chloromethyl)-3-[5-[2-(dimethylamino)ethoxy]-1h-indole-2-carbonyl]-5,7-dinitro-1,2-dihydrobenzo[e]indole-8-sulfonamide Chemical compound C1=C([N+]([O-])=O)C2=CC([N+]([O-])=O)=C(S(N)(=O)=O)C=C2C(C(CCl)C2)=C1N2C(=O)C1=CC2=CC(OCCN(C)C)=CC=C2N1 PXLRAEBBNSSDSC-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
• 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
• 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
• 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
• 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
• INPLUHLKGCCAIZ-UHFFFAOYSA-N 2,3-dihydro-1h-benzo[e]indole-7-carboxamide Chemical compound C1=CC2=CC(C(=O)N)=CC=C2C2=C1NCC2 INPLUHLKGCCAIZ-UHFFFAOYSA-N 0.000 claims 1
• BPADEPMRAXEFRM-UHFFFAOYSA-N 2-[[2-[1-(chloromethyl)-5-nitro-7-sulfamoyl-1,2-dihydrobenzo[e]indole-3-carbonyl]-1h-indol-5-yl]oxy]ethyl dihydrogen phosphate Chemical compound OP(=O)(O)OCCOC1=CC=C2NC(C(=O)N3CC(CCl)C=4C5=CC=C(C=C5C([N+]([O-])=O)=CC=43)S(=O)(=O)N)=CC2=C1 BPADEPMRAXEFRM-UHFFFAOYSA-N 0.000 claims 1
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 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
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-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
• 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
• 239000003112 inhibitor Substances 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
• 239000003814 drug Substances 0.000 abstract description 15
• 229940079593 drug Drugs 0.000 abstract description 8
• 230000007954 hypoxia Effects 0.000 abstract description 8
• 230000005855 radiation Effects 0.000 abstract description 7
• 238000002360 preparation method Methods 0.000 abstract description 5
• 229940041181 antineoplastic drug Drugs 0.000 abstract description 4
• YJSNSTMRPIVBKY-UHFFFAOYSA-N 1-nitro-2,3-dihydro-1h-benzo[e]indole Chemical class C1=CC=CC2=C3C([N+](=O)[O-])CNC3=CC=C21 YJSNSTMRPIVBKY-UHFFFAOYSA-N 0.000 abstract description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 458
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 345
• 239000000203 mixture Substances 0.000 description 238
• 235000019439 ethyl acetate Nutrition 0.000 description 229
• 238000005481 NMR spectroscopy Methods 0.000 description 205
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 196
• 239000000243 solution Substances 0.000 description 180
• 229910052757 nitrogen Inorganic materials 0.000 description 170
• 229910052799 carbon Inorganic materials 0.000 description 154
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 133
• 239000003208 petroleum Substances 0.000 description 97
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 94
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 81
• 239000000741 silica gel Substances 0.000 description 75
• 229910002027 silica gel Inorganic materials 0.000 description 75
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 63
• 238000004587 chromatography analysis Methods 0.000 description 61
• 239000012267 brine Substances 0.000 description 58
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