NO313381B1 - Bis (akridinkarboksamid) og bis (fenazinkarboksamid), derivat derav, deres fremstilling, farmasöytiske blandinger og anvendelsederav - Google Patents

Info

Publication number

NO313381B1

NO313381B1 NO19991833A NO991833A NO313381B1 NO 313381 B1 NO313381 B1 NO 313381B1 NO 19991833 A NO19991833 A NO 19991833A NO 991833 A NO991833 A NO 991833A NO 313381 B1 NO313381 B1 NO 313381B1

Authority

NO

Norway

Prior art keywords

bis

carboxamide

propyl

methylamine

arh

Prior art date

1996-10-18

Links

• Espacenet
• Global Dossier
• Discuss

• KPZYYKDXZKFBQU-UHFFFAOYSA-N phenazine-1-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)N)=CC=CC3=NC2=C1 KPZYYKDXZKFBQU-UHFFFAOYSA-N 0.000 title claims abstract description 24
• 229940125665 acridine carboxamide Drugs 0.000 title claims abstract description 6
• 238000002360 preparation method Methods 0.000 title claims description 87
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
• XBGNERSKEKDZDS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)NCCN(C)C)=CC=CC3=CC2=C1 XBGNERSKEKDZDS-UHFFFAOYSA-N 0.000 title abstract description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 84
• -1 methylenedioxy group Chemical group 0.000 claims abstract description 43
• 150000003839 salts Chemical class 0.000 claims abstract description 31
• 239000002253 acid Substances 0.000 claims abstract description 24
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 16
• 229910052736 halogen Chemical group 0.000 claims abstract description 13
• 150000002367 halogens Chemical group 0.000 claims abstract description 12
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
• 230000000259 anti-tumor effect Effects 0.000 claims abstract description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 2
• 229910052739 hydrogen Inorganic materials 0.000 claims description 764
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 128
• 229910052799 carbon Inorganic materials 0.000 claims description 98
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 79
• 238000000034 method Methods 0.000 claims description 67
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
• 150000001412 amines Chemical class 0.000 claims description 20
• 229910052801 chlorine Inorganic materials 0.000 claims description 20
• 150000003857 carboxamides Chemical group 0.000 claims description 10
• JGCSKOVQDXEQHI-UHFFFAOYSA-N phenazine-1-carboxylic acid Chemical class C1=CC=C2N=C3C(C(=O)O)=CC=CC3=NC2=C1 JGCSKOVQDXEQHI-UHFFFAOYSA-N 0.000 claims description 10
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 9
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 8
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 229960005141 piperazine Drugs 0.000 claims description 4
• OOGYVVYCCYJADG-UHFFFAOYSA-N acridine-1-carboxylic acid Chemical compound C1=CC=C2C=C3C(C(=O)O)=CC=CC3=NC2=C1 OOGYVVYCCYJADG-UHFFFAOYSA-N 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 239000000126 substance Substances 0.000 claims description 3
• 241001465754 Metazoa Species 0.000 claims description 2
• AORNIVFSXFONEC-UHFFFAOYSA-N acridine-1-carboxamide Chemical class C1=CC=C2C=C3C(C(=O)N)=CC=CC3=NC2=C1 AORNIVFSXFONEC-UHFFFAOYSA-N 0.000 claims description 2
• 229940126601 medicinal product Drugs 0.000 claims description 2
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 claims description 2
• KCBDLLNCTLQLPL-UHFFFAOYSA-N acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)N)=CC=CC3=CC2=C1 KCBDLLNCTLQLPL-UHFFFAOYSA-N 0.000 claims 5
• FXVNOBHHTGCEQM-UHFFFAOYSA-N 9-methylphenazine-1-carboxamide Chemical compound C1=CC(C(N)=O)=C2N=C3C(C)=CC=CC3=NC2=C1 FXVNOBHHTGCEQM-UHFFFAOYSA-N 0.000 claims 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
• QERPXTFYBOVNIT-UHFFFAOYSA-N 3-chlorophenazine-1-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)N)=CC(Cl)=CC3=NC2=C1 QERPXTFYBOVNIT-UHFFFAOYSA-N 0.000 claims 1
• OQMTXUVWXQZPHZ-UHFFFAOYSA-N 4-methylphenazine-1-carboxamide Chemical compound C1=CC=C2N=C3C(C)=CC=C(C(N)=O)C3=NC2=C1 OQMTXUVWXQZPHZ-UHFFFAOYSA-N 0.000 claims 1
• MPLPENLZKBHAMC-UHFFFAOYSA-N 5-methylacridine-4-carboxamide Chemical compound C1=CC(C(N)=O)=C2N=C3C(C)=CC=CC3=CC2=C1 MPLPENLZKBHAMC-UHFFFAOYSA-N 0.000 claims 1
• JFNJUBCNTOTDDB-UHFFFAOYSA-N 6-chlorophenazine-1-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)N)=CC=CC3=NC2=C1Cl JFNJUBCNTOTDDB-UHFFFAOYSA-N 0.000 claims 1
• PZBHEYZCCDJGFS-UHFFFAOYSA-N 6-methylphenazine-1-carboxamide Chemical compound C1=CC=C2N=C3C(C)=CC=CC3=NC2=C1C(N)=O PZBHEYZCCDJGFS-UHFFFAOYSA-N 0.000 claims 1
• VGHRHIHXTONTPK-UHFFFAOYSA-N 7-chlorophenazine-1-carboxamide Chemical compound ClC1=CC=C2N=C3C(C(=O)N)=CC=CC3=NC2=C1 VGHRHIHXTONTPK-UHFFFAOYSA-N 0.000 claims 1
• DYPMNLITWJYPQO-UHFFFAOYSA-N 7-methoxyphenazine-1-carboxamide Chemical compound NC(=O)C1=CC=CC2=NC3=CC(OC)=CC=C3N=C21 DYPMNLITWJYPQO-UHFFFAOYSA-N 0.000 claims 1
• IUEFEUVRIAOTRQ-UHFFFAOYSA-N 7-methylphenazine-1-carboxamide Chemical compound NC(=O)C1=CC=CC2=NC3=CC(C)=CC=C3N=C21 IUEFEUVRIAOTRQ-UHFFFAOYSA-N 0.000 claims 1
• OGXONDPWSNYAIT-UHFFFAOYSA-N 8-methoxyphenazine-1-carboxamide Chemical compound C1=CC=C(C(N)=O)C2=NC3=CC(OC)=CC=C3N=C21 OGXONDPWSNYAIT-UHFFFAOYSA-N 0.000 claims 1
• UGRALQNBBBYVHQ-UHFFFAOYSA-N 8-methylphenazine-1-carboxamide Chemical compound C1=CC=C(C(N)=O)C2=NC3=CC(C)=CC=C3N=C21 UGRALQNBBBYVHQ-UHFFFAOYSA-N 0.000 claims 1
• IAPWGGQZIUEERE-UHFFFAOYSA-N 9-chlorophenazine-1-carboxamide Chemical compound C1=CC(Cl)=C2N=C3C(C(=O)N)=CC=CC3=NC2=C1 IAPWGGQZIUEERE-UHFFFAOYSA-N 0.000 claims 1
• JNMPFZVFHIJSHN-UHFFFAOYSA-N 9-fluorophenazine-1-carboxamide Chemical compound NC(=O)c1cccc2nc3cccc(F)c3nc12 JNMPFZVFHIJSHN-UHFFFAOYSA-N 0.000 claims 1
• MJRFBSHDKBCQOC-UHFFFAOYSA-N 9-methoxyphenazine-1-carboxamide Chemical compound C1=CC(C(N)=O)=C2N=C3C(OC)=CC=CC3=NC2=C1 MJRFBSHDKBCQOC-UHFFFAOYSA-N 0.000 claims 1
• QEXMUDIBEKFQDA-UHFFFAOYSA-N acridine-2-carboxamide Chemical compound C1=CC=CC2=CC3=CC(C(=O)N)=CC=C3N=C21 QEXMUDIBEKFQDA-UHFFFAOYSA-N 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• HBUAKGFNHSQHSX-UHFFFAOYSA-N phenazine-2-carboxamide Chemical compound C1=CC=CC2=NC3=CC(C(=O)N)=CC=C3N=C21 HBUAKGFNHSQHSX-UHFFFAOYSA-N 0.000 claims 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 6
• 239000002246 antineoplastic agent Substances 0.000 abstract description 4
• 230000000694 effects Effects 0.000 abstract description 3
• 125000004104 aryloxy group Chemical group 0.000 abstract description 2
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
• 239000003242 anti bacterial agent Substances 0.000 abstract 1
• 238000005481 NMR spectroscopy Methods 0.000 description 149
• 229910052757 nitrogen Inorganic materials 0.000 description 96
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 79
• 239000000460 chlorine Substances 0.000 description 75
• 238000005859 coupling reaction Methods 0.000 description 75
• 230000008878 coupling Effects 0.000 description 72
• 238000010168 coupling process Methods 0.000 description 72
• 230000004913 activation Effects 0.000 description 67
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
• 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 40
• 235000019439 ethyl acetate Nutrition 0.000 description 39
• 230000002829 reductive effect Effects 0.000 description 39
• 239000000243 solution Substances 0.000 description 39
• 239000003921 oil Substances 0.000 description 36
• 235000019198 oils Nutrition 0.000 description 36
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
• 239000000203 mixture Substances 0.000 description 32
• 239000007787 solid Substances 0.000 description 32
• 239000002904 solvent Substances 0.000 description 32
• 238000006243 chemical reaction Methods 0.000 description 29
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 28
• 239000011734 sodium Substances 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
• JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 23
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 22
• 229910001868 water Inorganic materials 0.000 description 22
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• 206010028980 Neoplasm Diseases 0.000 description 20
• 239000003208 petroleum Substances 0.000 description 20
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 17
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 16
• 150000003840 hydrochlorides Chemical class 0.000 description 16
• DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 14
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 229910002091 carbon monoxide Inorganic materials 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 11
• 238000000354 decomposition reaction Methods 0.000 description 11
• 239000003480 eluent Substances 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 238000007363 ring formation reaction Methods 0.000 description 10
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 9
• JPRPEGGFLLPQJB-UHFFFAOYSA-N 9-methylphenazine-1-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2N=C3C(C)=CC=CC3=NC2=C1 JPRPEGGFLLPQJB-UHFFFAOYSA-N 0.000 description 9
• PCNDJXKNXGMECE-UHFFFAOYSA-N phenazine Chemical class C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 9
• VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical class OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 238000002425 crystallisation Methods 0.000 description 8
• 230000008025 crystallization Effects 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 241000699670 Mus sp. Species 0.000 description 7
• NBIUCDPMOWCGIG-UHFFFAOYSA-N acridine-4-carboxylic acid Chemical class C1=CC=C2N=C3C(C(=O)O)=CC=CC3=CC2=C1 NBIUCDPMOWCGIG-UHFFFAOYSA-N 0.000 description 7
• 201000011510 cancer Diseases 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000003814 drug Substances 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 239000012458 free base Substances 0.000 description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
• VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 5
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
• 229930006000 Sucrose Natural products 0.000 description 5
• OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 5
• 239000006260 foam Substances 0.000 description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• 238000007254 oxidation reaction Methods 0.000 description 5
• 239000002798 polar solvent Substances 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 239000005720 sucrose Substances 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• WCZUOJVHIDLUIX-UHFFFAOYSA-N 1-chloro-n-[3-[3-[(1-chloro-5-methylacridine-4-carbonyl)amino]propyl-methylamino]propyl]-5-methylacridine-4-carboxamide Chemical compound C1=CC(C)=C2N=C3C(C(=O)NCCCN(CCCNC(=O)C=4C5=NC6=C(C)C=CC=C6C=C5C(Cl)=CC=4)C)=CC=C(Cl)C3=CC2=C1 WCZUOJVHIDLUIX-UHFFFAOYSA-N 0.000 description 4
• BLCYFJOUMZPEQG-UHFFFAOYSA-N 1-chloro-n-[3-[3-[(1-chloroacridine-4-carbonyl)amino]propyl-methylamino]propyl]acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)NCCCN(CCCNC(=O)C=4C5=NC6=CC=CC=C6C=C5C(Cl)=CC=4)C)=CC=C(Cl)C3=CC2=C1 BLCYFJOUMZPEQG-UHFFFAOYSA-N 0.000 description 4
• PBIDRTDEJPAXHY-UHFFFAOYSA-N 2-iodobenzene-1,3-dicarboxylic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1I PBIDRTDEJPAXHY-UHFFFAOYSA-N 0.000 description 4
• VEZVKDORRZQQGS-UHFFFAOYSA-N 3-methyl-n-[3-[methyl-[3-[(3-methylacridine-4-carbonyl)amino]propyl]amino]propyl]acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)NCCCN(CCCNC(=O)C=4C5=NC6=CC=CC=C6C=C5C=CC=4C)C)=C(C)C=CC3=CC2=C1 VEZVKDORRZQQGS-UHFFFAOYSA-N 0.000 description 4
• FVEHXLZVGOLWEI-UHFFFAOYSA-N 5-fluoro-n-[3-[3-[(5-fluoroacridine-4-carbonyl)amino]propyl-methylamino]propyl]acridine-4-carboxamide Chemical compound C1=CC(F)=C2N=C3C(C(=O)NCCCN(CCCNC(=O)C=4C5=NC6=C(F)C=CC=C6C=C5C=CC=4)C)=CC=CC3=CC2=C1 FVEHXLZVGOLWEI-UHFFFAOYSA-N 0.000 description 4
• MOMKGDFIUWTTFO-UHFFFAOYSA-N 5-methylacridine-4-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2N=C3C(C)=CC=CC3=CC2=C1 MOMKGDFIUWTTFO-UHFFFAOYSA-N 0.000 description 4
• TUEKQGTZNKPMBA-UHFFFAOYSA-N 7-fluoro-n-[3-[3-[(7-fluoroacridine-4-carbonyl)amino]propyl-methylamino]propyl]acridine-4-carboxamide Chemical compound FC1=CC=C2N=C3C(C(=O)NCCCN(CCCNC(=O)C=4C5=NC6=CC=C(F)C=C6C=C5C=CC=4)C)=CC=CC3=CC2=C1 TUEKQGTZNKPMBA-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 239000005711 Benzoic acid Substances 0.000 description 4
• 101150041968 CDC13 gene Proteins 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 150000001251 acridines Chemical class 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 239000010949 copper Substances 0.000 description 4
• DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 150000007928 imidazolide derivatives Chemical class 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• BXXLTVBTDZXPTN-UHFFFAOYSA-N methyl 2-iodobenzoate Chemical compound COC(=O)C1=CC=CC=C1I BXXLTVBTDZXPTN-UHFFFAOYSA-N 0.000 description 4
• KMBPCQSCMCEPMU-UHFFFAOYSA-N n'-(3-aminopropyl)-n'-methylpropane-1,3-diamine Chemical compound NCCCN(C)CCCN KMBPCQSCMCEPMU-UHFFFAOYSA-N 0.000 description 4
• 230000003647 oxidation Effects 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 125000001424 substituent group Chemical group 0.000 description 4
• 239000006188 syrup Substances 0.000 description 4
• 235000020357 syrup Nutrition 0.000 description 4
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