CA2584702A1 - Nitrobenzindoles and their use in cancer therapy - Google Patents

Info

Publication number

CA2584702A1

CA2584702A1 CA002584702A CA2584702A CA2584702A1 CA 2584702 A1 CA2584702 A1 CA 2584702A1 CA 002584702 A CA002584702 A CA 002584702A CA 2584702 A CA2584702 A CA 2584702A CA 2584702 A1 CA2584702 A1 CA 2584702A1

Authority

CA

Canada

Prior art keywords

indole

dihydro

benzo

chloromethyl

carbonyl

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• 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 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 214
• 239000007787 solid Substances 0.000 claims description 163
• 150000001875 compounds Chemical class 0.000 claims description 127
• FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 50
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 40
• -1 1-(Chloromethyl)-3-{5-[2-(dimethylamino)ethoxy] indol-2-carbonyl}-N,N-dimethyl-nitro-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide Chemical compound 0.000 claims description 39
• 206010028980 Neoplasm Diseases 0.000 claims description 39
• 230000001146 hypoxic effect Effects 0.000 claims description 39
• 238000000034 method Methods 0.000 claims description 36
• 238000011282 treatment Methods 0.000 claims description 30
• 210000004027 cell Anatomy 0.000 claims description 26
• 235000010333 potassium nitrate Nutrition 0.000 claims description 25
• 229910052740 iodine Inorganic materials 0.000 claims description 22
• 125000003277 amino group Chemical group 0.000 claims description 21
• UOORRWUZONOOLO-OWOJBTEDSA-N (E)-1,3-dichloropropene Chemical compound ClC\C=C\Cl UOORRWUZONOOLO-OWOJBTEDSA-N 0.000 claims description 20
• 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 description 20
• UOORRWUZONOOLO-UHFFFAOYSA-N telone II Natural products ClCC=CCl UOORRWUZONOOLO-UHFFFAOYSA-N 0.000 claims description 20
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
• 229910000104 sodium hydride Inorganic materials 0.000 claims description 18
• 102000004459 Nitroreductase Human genes 0.000 claims description 16
• 108020001162 nitroreductase Proteins 0.000 claims description 16
• 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 description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 15
• 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 claims description 14
• 201000011510 cancer Diseases 0.000 claims description 13
• 238000006722 reduction reaction Methods 0.000 claims description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
• 229910052794 bromium Inorganic materials 0.000 claims description 12
• 238000006243 chemical reaction Methods 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 12
• 235000011149 sulphuric acid Nutrition 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 12
• 229910019142 PO4 Inorganic materials 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 238000002560 therapeutic procedure Methods 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
• 239000010452 phosphate Substances 0.000 claims description 9
• 210000004881 tumor cell Anatomy 0.000 claims description 9
• 229910052721 tungsten Inorganic materials 0.000 claims description 8
• 229940127089 cytotoxic agent Drugs 0.000 claims description 7
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 7
• 125000000217 alkyl group Chemical group 0.000 claims description 6
• 230000004060 metabolic process Effects 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• WNQKKFNKWGTFIX-UHFFFAOYSA-N 1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-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=CC(C=C(C(=C2OC)OC)OC)=C2N1 WNQKKFNKWGTFIX-UHFFFAOYSA-N 0.000 claims description 5
• 208000037841 lung tumor Diseases 0.000 claims description 5
• 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 description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 238000001959 radiotherapy Methods 0.000 claims description 5
• 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 description 4
• 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 description 4
• 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 description 4
• 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 description 4
• RWAFGSMUNQVMEO-UHFFFAOYSA-N 2-[[1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-1,2-dihydrobenzo[e]indol-7-yl]sulfonylamino]ethyl dihydrogen phosphate Chemical compound C1=C([N+]([O-])=O)C2=CC(S(=O)(=O)NCCOP(O)(O)=O)=CC=C2C(C(CCl)C2)=C1N2C(=O)C1=CC(C=C(C(=C2OC)OC)OC)=C2N1 RWAFGSMUNQVMEO-UHFFFAOYSA-N 0.000 claims description 4
• 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 description 4
• 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 description 4
• 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 description 4
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 4
• 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 description 4
• 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 description 4
• 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 4
• 239000002671 adjuvant Substances 0.000 claims description 4
• 239000000872 buffer Substances 0.000 claims description 4
• 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 description 4
• 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 description 4
• 230000000802 nitrating effect Effects 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
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
• 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 description 3
• 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 description 3
• 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 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
• 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 3
• 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 description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• 210000000481 breast Anatomy 0.000 claims description 3
• 230000026030 halogenation Effects 0.000 claims description 3
• 238000005658 halogenation reaction Methods 0.000 claims description 3
• 125000000623 heterocyclic group Chemical group 0.000 claims description 3
• 238000001727 in vivo Methods 0.000 claims description 3
• 208000032839 leukemia Diseases 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 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
• 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
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
• 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 description 2
• 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 description 2
• 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 description 2
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