CA2392873A1 - Benzo[a]phenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase i and ii - Google Patents
Benzo[a]phenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase i and ii Download PDFInfo
- Publication number
- CA2392873A1 CA2392873A1 CA002392873A CA2392873A CA2392873A1 CA 2392873 A1 CA2392873 A1 CA 2392873A1 CA 002392873 A CA002392873 A CA 002392873A CA 2392873 A CA2392873 A CA 2392873A CA 2392873 A1 CA2392873 A1 CA 2392873A1
- Authority
- CA
- Canada
- Prior art keywords
- benzo
- phenazine
- carboxylic acid
- amide
- dimethylamino
- Prior art date
- 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
- 239000003112 inhibitor Substances 0.000 title claims abstract description 19
- QDGSQQMUZONPER-UHFFFAOYSA-N benzo[a]phenazine-11-carboxamide Chemical class C1=CC=CC2=C(N=C3C(C(=O)N)=CC=CC3=N3)C3=CC=C21 QDGSQQMUZONPER-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 211
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 30
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 25
- 102000003915 DNA Topoisomerases Human genes 0.000 claims abstract description 22
- 108090000323 DNA Topoisomerases Proteins 0.000 claims abstract description 22
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 claims abstract description 21
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 claims abstract description 21
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 14
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 13
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 11
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 3
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 (2-dimethylamino-ethyl)-amide 4-Hydroxy-benzo[a]phenazine-11-carboxylic acid (2-dimethylamino-ethyl)-amide Chemical compound 0.000 claims description 94
- GMAMQZVLSLMBFK-UHFFFAOYSA-N 4-methoxybenzo[a]phenazine-11-carboxylic acid Chemical compound C1=CC2=NC3=CC=CC(C(O)=O)=C3N=C2C2=C1C(OC)=CC=C2 GMAMQZVLSLMBFK-UHFFFAOYSA-N 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 33
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 7
- QUQUQZHBQSXVDN-UHFFFAOYSA-N 4-aminobenzo[a]phenazine-11-carboxylic acid Chemical compound C1=CC2=NC3=CC=CC(C(O)=O)=C3N=C2C2=C1C(N)=CC=C2 QUQUQZHBQSXVDN-UHFFFAOYSA-N 0.000 claims description 6
- SOFSGGQTMQBVNT-UHFFFAOYSA-N 4-azidobenzo[a]phenazine-11-carboxylic acid Chemical compound [N-]=[N+]=NC1=CC=CC2=C(N=C3C(C(=O)O)=CC=CC3=N3)C3=CC=C21 SOFSGGQTMQBVNT-UHFFFAOYSA-N 0.000 claims description 6
- KFTKDMSJDGPIQK-UHFFFAOYSA-N 4-methylbenzo[a]phenazine-11-carboxylic acid Chemical compound C1=CC2=NC3=CC=CC(C(O)=O)=C3N=C2C2=C1C(C)=CC=C2 KFTKDMSJDGPIQK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 238000007385 chemical modification Methods 0.000 claims description 6
- KETQAJRQOHHATG-UHFFFAOYSA-N 1,2-naphthoquinone Chemical compound C1=CC=C2C(=O)C(=O)C=CC2=C1 KETQAJRQOHHATG-UHFFFAOYSA-N 0.000 claims description 5
- 229940105324 1,2-naphthoquinone Drugs 0.000 claims description 5
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 claims description 5
- 235000010233 benzoic acid Nutrition 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- LKHUWHQEMJTELV-UHFFFAOYSA-N 4-fluorobenzo[a]phenazine-11-carboxylic acid Chemical compound FC1=CC=CC2=C(N=C3C(C(=O)O)=CC=CC3=N3)C3=CC=C21 LKHUWHQEMJTELV-UHFFFAOYSA-N 0.000 claims description 4
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- IBMHXIHITBJPCY-UHFFFAOYSA-N methyl 3-(dimethylamino)-2-[(4-methoxybenzo[a]phenazine-11-carbonyl)amino]propanoate Chemical compound COC1=CC=CC2=C(N=C3C(C(=O)NC(CN(C)C)C(=O)OC)=CC=CC3=N3)C3=CC=C21 IBMHXIHITBJPCY-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 229940121375 antifungal agent Drugs 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000000840 anti-viral effect Effects 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims 2
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- ZJUVFEFUJHQCGY-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-ethoxybenzo[a]phenazine-11-carboxamide Chemical compound C1=CC2=NC3=CC=CC(C(=O)NCCN(C)C)=C3N=C2C2=C1C(OCC)=CC=C2 ZJUVFEFUJHQCGY-UHFFFAOYSA-N 0.000 description 1
- OYPDBVPVJYEKLP-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-methoxy-10-(methylamino)benzo[a]phenazine-11-carboxamide Chemical compound C1=CC=C2C3=NC4=C(C(=O)NCCN(C)C)C(NC)=CC=C4N=C3C=CC2=C1OC OYPDBVPVJYEKLP-UHFFFAOYSA-N 0.000 description 1
- NWBJUOIOERGURY-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-methoxy-8-methylbenzo[a]phenazine-11-carboxamide Chemical compound C1=CC2=NC3=C(C)C=CC(C(=O)NCCN(C)C)=C3N=C2C2=C1C(OC)=CC=C2 NWBJUOIOERGURY-UHFFFAOYSA-N 0.000 description 1
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- DVCMITYIGQXEFS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-methylsulfonylbenzo[a]phenazine-11-carboxamide Chemical compound CS(=O)(=O)C1=CC=CC2=C(N=C3C(C(=O)NCCN(C)C)=CC=CC3=N3)C3=CC=C21 DVCMITYIGQXEFS-UHFFFAOYSA-N 0.000 description 1
- CHQHTDSEZJZYED-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-nitrobenzo[a]phenazine-11-carboxamide Chemical compound [O-][N+](=O)C1=CC=CC2=C(N=C3C(C(=O)NCCN(C)C)=CC=CC3=N3)C3=CC=C21 CHQHTDSEZJZYED-UHFFFAOYSA-N 0.000 description 1
- QKCJOMCOKABQIO-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-phenylmethoxybenzo[a]phenazine-11-carboxamide Chemical compound C=1C=CC2=C3N=C4C(C(=O)NCCN(C)C)=CC=CC4=NC3=CC=C2C=1OCC1=CC=CC=C1 QKCJOMCOKABQIO-UHFFFAOYSA-N 0.000 description 1
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- GVEYKYRTFVKZLF-UHFFFAOYSA-N n-[2-(dimethylamino)propyl]-4-methoxybenzo[a]phenazine-11-carboxamide Chemical compound C1=CC2=NC3=CC=CC(C(=O)NCC(C)N(C)C)=C3N=C2C2=C1C(OC)=CC=C2 GVEYKYRTFVKZLF-UHFFFAOYSA-N 0.000 description 1
- NKQGFHJQWKUPPI-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-4-methoxybenzo[a]phenazine-11-carboxamide Chemical compound C1=CC2=NC3=CC=CC(C(=O)NCCCN(C)C)=C3N=C2C2=C1C(OC)=CC=C2 NKQGFHJQWKUPPI-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 150000002988 phenazines Chemical class 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- ICZHJFWIOPYQCA-UHFFFAOYSA-N pirkle's alcohol Chemical compound C1=CC=C2C(C(O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 ICZHJFWIOPYQCA-UHFFFAOYSA-N 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000003579 shift reagent Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 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 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-N tert-butyl hydrogen carbonate Chemical compound CC(C)(C)OC(O)=O XKXIQBVKMABYQJ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- YJSKZIATOGOJEB-UHFFFAOYSA-N thieno[2,3-b]pyrazine Chemical compound C1=CN=C2SC=CC2=N1 YJSKZIATOGOJEB-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/46—Phenazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9928542.1 | 1999-12-02 | ||
GBGB9928542.1A GB9928542D0 (en) | 1999-12-02 | 1999-12-02 | Pharmaceutical compounds |
PCT/GB2000/004609 WO2001046157A1 (en) | 1999-12-02 | 2000-12-01 | Benzo[a]phenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase i and ii |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2392873A1 true CA2392873A1 (en) | 2001-06-28 |
Family
ID=10865607
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002392873A Abandoned CA2392873A1 (en) | 1999-12-02 | 2000-12-01 | Benzo[a]phenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase i and ii |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP1240148A1 (xx) |
JP (1) | JP2003518103A (xx) |
KR (1) | KR100767613B1 (xx) |
CN (1) | CN1304380C (xx) |
AU (1) | AU784397B2 (xx) |
BR (1) | BR0016093A (xx) |
CA (1) | CA2392873A1 (xx) |
GB (2) | GB9928542D0 (xx) |
HK (1) | HK1046133B (xx) |
HU (1) | HUP0300392A3 (xx) |
MX (1) | MXPA02005476A (xx) |
MY (1) | MY136029A (xx) |
PL (1) | PL356482A1 (xx) |
TW (1) | TWI280242B (xx) |
WO (1) | WO2001046157A1 (xx) |
ZA (1) | ZA200204296B (xx) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2433071A (en) * | 2005-12-05 | 2007-06-13 | Kontrakt Technology Ltd | Organic acids comprising planar conjugated heterocyclic molecular system, & photoelectric layer thereof with rodlike supramolecules for use in solar cell |
CN102898388B (zh) * | 2012-09-26 | 2014-12-03 | 浙江工业大学 | 一种合成取代苯并[α]吩嗪类化合物的方法 |
CN103360329B (zh) * | 2013-07-18 | 2015-11-18 | 中国科学院南海海洋研究所 | 一类吩嗪化合物及其在制备抗肿瘤药物中的应用 |
CN106554321B (zh) * | 2015-09-25 | 2019-05-28 | 陆源 | 一种吩嗪类物质、其制备方法及其应用 |
CN113461623A (zh) * | 2021-07-14 | 2021-10-01 | 长江大学 | 一种抗病毒化合物及其制备方法和应用 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5696131A (en) * | 1993-01-22 | 1997-12-09 | Xenova Limited | Treatment of cancers |
AU691787B2 (en) * | 1992-05-28 | 1998-05-28 | Xenova Limited | Treatment of cancers |
PL332416A1 (en) * | 1996-09-23 | 1999-09-13 | Rutgers | Substituted heterocyclic compounds as anticarcinogenic agents |
WO1998045272A1 (en) * | 1997-04-07 | 1998-10-15 | Latrobe University | Topoisomerase inhibitors |
-
1999
- 1999-12-02 GB GBGB9928542.1A patent/GB9928542D0/en not_active Ceased
-
2000
- 2000-12-01 HU HU0300392A patent/HUP0300392A3/hu unknown
- 2000-12-01 CN CNB008187096A patent/CN1304380C/zh not_active Expired - Fee Related
- 2000-12-01 WO PCT/GB2000/004609 patent/WO2001046157A1/en active Application Filing
- 2000-12-01 KR KR1020027007033A patent/KR100767613B1/ko not_active IP Right Cessation
- 2000-12-01 PL PL00356482A patent/PL356482A1/xx not_active Application Discontinuation
- 2000-12-01 GB GB0215275A patent/GB2373499B/en not_active Expired - Fee Related
- 2000-12-01 CA CA002392873A patent/CA2392873A1/en not_active Abandoned
- 2000-12-01 MX MXPA02005476A patent/MXPA02005476A/es not_active Application Discontinuation
- 2000-12-01 EP EP00979799A patent/EP1240148A1/en not_active Withdrawn
- 2000-12-01 AU AU17184/01A patent/AU784397B2/en not_active Ceased
- 2000-12-01 BR BR0016093-8A patent/BR0016093A/pt not_active IP Right Cessation
- 2000-12-01 MY MYPI20005670A patent/MY136029A/en unknown
- 2000-12-01 JP JP2001547068A patent/JP2003518103A/ja active Pending
- 2000-12-02 TW TW089125715A patent/TWI280242B/zh not_active IP Right Cessation
-
2002
- 2002-05-29 ZA ZA200204296A patent/ZA200204296B/en unknown
- 2002-10-10 HK HK02107392.7A patent/HK1046133B/zh not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
GB0215275D0 (en) | 2002-08-14 |
TWI280242B (en) | 2007-05-01 |
HK1046133B (zh) | 2005-04-15 |
HUP0300392A2 (hu) | 2003-07-28 |
HUP0300392A3 (en) | 2003-09-29 |
ZA200204296B (en) | 2003-05-29 |
GB2373499B (en) | 2004-11-17 |
CN1304380C (zh) | 2007-03-14 |
AU1718401A (en) | 2001-07-03 |
GB9928542D0 (en) | 2000-02-02 |
PL356482A1 (en) | 2004-06-28 |
WO2001046157A1 (en) | 2001-06-28 |
KR100767613B1 (ko) | 2007-10-19 |
HK1046133A1 (en) | 2002-12-27 |
MXPA02005476A (es) | 2003-09-22 |
BR0016093A (pt) | 2002-08-20 |
MY136029A (en) | 2008-07-31 |
KR20020070305A (ko) | 2002-09-05 |
GB2373499A (en) | 2002-09-25 |
JP2003518103A (ja) | 2003-06-03 |
AU784397B2 (en) | 2006-03-23 |
EP1240148A1 (en) | 2002-09-18 |
CN1433406A (zh) | 2003-07-30 |
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