NO314304B1 - Isokinoloner og fremgangsmåte for fremstilling derav - Google Patents

Isokinoloner og fremgangsmåte for fremstilling derav Download PDF

Info

Publication number: NO314304B1
Authority: NO; Norway
Prior art keywords: dione; benzo; isoquinoline; hydroxy; mmol
Prior art date: 1996-11-01

Application number

NO19992104A

Other languages

English (en)

Norwegian (no)

Other versions

NO992104D0 (no

NO992104L (no

Inventor

Albert Kudzoi Amegadzie

Maureen Elizabeth Carey

John Michael Domagala

Liren Huang

Ronald George Micetich

Rajeshwar Singh

Michael Andrew Stier

Arkadii Vaisburg

Joseph Peter Sanchez

Original Assignee

Warner Lambert Co

Priority date (The priority date 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 date listed.)

1996-11-01

Filing date

1999-04-30

Publication date

2003-03-03

1999-04-30 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

1999-04-30 Publication of NO992104D0 publication Critical patent/NO992104D0/no

1999-04-30 Publication of NO992104L publication Critical patent/NO992104L/no

2003-03-03 Publication of NO314304B1 publication Critical patent/NO314304B1/no

Links

238000000034 method Methods 0.000 title description 92
238000002360 preparation method Methods 0.000 title description 15
VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 title description 2
230000008569 process Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 289
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 48
238000006243 chemical reaction Methods 0.000 claims description 48
-1 4-aminopiperidin-1-yl Chemical group 0.000 claims description 40
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
229910052739 hydrogen Inorganic materials 0.000 claims description 30
125000000623 heterocyclic group Chemical group 0.000 claims description 28
229910052794 bromium Inorganic materials 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 22
239000000460 chlorine Substances 0.000 claims description 20
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 16
229910052801 chlorine Inorganic materials 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
229910052731 fluorine Inorganic materials 0.000 claims description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000005842 heteroatom Chemical group 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000002757 morpholinyl group Chemical group 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
VCNMFLKYEGUCKM-UHFFFAOYSA-N 2-hydroxy-5-methoxy-6-(4-methylpiperazin-1-yl)benzo[de]isoquinoline-1,3-dione Chemical compound COC1=CC(=C23)C(=O)N(O)C(=O)C3=CC=CC2=C1N1CCN(C)CC1 VCNMFLKYEGUCKM-UHFFFAOYSA-N 0.000 claims description 4
DWUBPAASNUUBCU-UHFFFAOYSA-N 2-hydroxy-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCCC1 DWUBPAASNUUBCU-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[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
IDZVLKHXQYTTOG-UHFFFAOYSA-N 2,5-dihydroxy-4-methyl-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C=3C=CC=C2C(=O)N(O)C(=O)C=1C(C)=C(O)C=3N1CCCCC1 IDZVLKHXQYTTOG-UHFFFAOYSA-N 0.000 claims description 3
LAKUFAAPCUJNPX-UHFFFAOYSA-N 2-hydroxy-1,3-dioxo-6-pyrrolidin-1-ylbenzo[de]isoquinoline-5-carbonitrile Chemical compound N#CC1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCC1 LAKUFAAPCUJNPX-UHFFFAOYSA-N 0.000 claims description 3
UGJDLNPCBHXMOA-UHFFFAOYSA-N 2-hydroxy-5-nitro-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=CC([N+]([O-])=O)=CC=1C(=O)N(O)C(=O)C2=CC=C3N1CCCC1 UGJDLNPCBHXMOA-UHFFFAOYSA-N 0.000 claims description 3
DQEDYLYGNXBYEL-UHFFFAOYSA-N 2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCC1 DQEDYLYGNXBYEL-UHFFFAOYSA-N 0.000 claims description 3
KFLBGPGBDPQKHA-UHFFFAOYSA-N 5,6-dichloro-2-hydroxy-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=C(Cl)C(Cl)=CC=1C(=O)N(O)C(=O)C2=CC=C3N1CCCC1 KFLBGPGBDPQKHA-UHFFFAOYSA-N 0.000 claims description 3
PXAQYRGXLYOJMD-UHFFFAOYSA-N 5-amino-2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound NC1=CC(=C23)C(=O)N(O)C(=O)C3=CC=CC2=C1N1CCCC1 PXAQYRGXLYOJMD-UHFFFAOYSA-N 0.000 claims description 3
NNTARCMWJIHGAU-UHFFFAOYSA-N 5-bromo-2-hydroxy-6-(3-methylpiperidin-1-yl)benzo[de]isoquinoline-1,3-dione Chemical compound C1C(C)CCCN1C1=C(Br)C=C2C3=C1C=CC=C3C(=O)N(O)C2=O NNTARCMWJIHGAU-UHFFFAOYSA-N 0.000 claims description 3
GWXFJYZUOJYIKL-UHFFFAOYSA-N 5-bromo-2-hydroxy-6-(4-methylpiperazin-1-yl)benzo[de]isoquinoline-1,3-dione Chemical compound C1CN(C)CCN1C1=C(Br)C=C2C3=C1C=CC=C3C(=O)N(O)C2=O GWXFJYZUOJYIKL-UHFFFAOYSA-N 0.000 claims description 3
PKACYCVWDJAOII-UHFFFAOYSA-N 5-bromo-2-hydroxy-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound BrC1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCCC1 PKACYCVWDJAOII-UHFFFAOYSA-N 0.000 claims description 3
150000001298 alcohols Chemical class 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 3
SURCGQGDUADKBL-UHFFFAOYSA-N 2-(2-hydroxyethylamino)-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(NCCO)C2=O)=O)=C3C2=CC=CC3=C1 SURCGQGDUADKBL-UHFFFAOYSA-N 0.000 claims description 2
FWFSQTLRNHWDCI-UHFFFAOYSA-N 2-hydroxy-1,3-dioxo-6-piperidin-1-ylbenzo[de]isoquinoline-5-carbonitrile Chemical compound N#CC1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCCC1 FWFSQTLRNHWDCI-UHFFFAOYSA-N 0.000 claims description 2
CPMFJQQUQBZYRL-UHFFFAOYSA-N 2-hydroxy-5,8-dinitro-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(=C23)C(=O)N(O)C(=O)C2=CC([N+]([O-])=O)=CC3=C1N1CCCC1 CPMFJQQUQBZYRL-UHFFFAOYSA-N 0.000 claims description 2
CFGXDQWLLZACHI-UHFFFAOYSA-N 2-hydroxy-5-methoxy-6-morpholin-4-ylbenzo[de]isoquinoline-1,3-dione Chemical compound COC1=CC(=C23)C(=O)N(O)C(=O)C3=CC=CC2=C1N1CCOCC1 CFGXDQWLLZACHI-UHFFFAOYSA-N 0.000 claims description 2
IMHJUABQUNHEMK-UHFFFAOYSA-N 2-hydroxy-5-methoxy-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=2C3=CC(OC)=CC=2C(=O)N(O)C(=O)C1=CC=C3N1CCCC1 IMHJUABQUNHEMK-UHFFFAOYSA-N 0.000 claims description 2
JPUIXQUVMINRFJ-UHFFFAOYSA-N 2-hydroxy-5-nitro-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCC1 JPUIXQUVMINRFJ-UHFFFAOYSA-N 0.000 claims description 2
OUDNMYOPYPGBOD-UHFFFAOYSA-N 2-hydroxy-6-(4-methylpiperazin-1-yl)benzo[de]isoquinoline-1,3-dione Chemical compound C1CN(C)CCN1C1=CC=C2C3=C1C=CC=C3C(=O)N(O)C2=O OUDNMYOPYPGBOD-UHFFFAOYSA-N 0.000 claims description 2
HXRJLYQLUFXROP-UHFFFAOYSA-N 2-hydroxy-6-morpholin-4-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCOCC1 HXRJLYQLUFXROP-UHFFFAOYSA-N 0.000 claims description 2
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
KUFPJTLNHJRYJE-UHFFFAOYSA-N 5-bromo-2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound BrC1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCC1 KUFPJTLNHJRYJE-UHFFFAOYSA-N 0.000 claims description 2
LKSHJTJDRCAWEU-UHFFFAOYSA-N 5-chloro-2-hydroxy-6-(3-methoxypyrrolidin-1-yl)benzo[de]isoquinoline-1,3-dione Chemical compound C1C(OC)CCN1C1=C(Cl)C=C2C3=C1C=CC=C3C(=O)N(O)C2=O LKSHJTJDRCAWEU-UHFFFAOYSA-N 0.000 claims description 2
HVCIKRLEWIFUPO-UHFFFAOYSA-N 5-chloro-2-hydroxy-8-nitro-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=CC([N+]([O-])=O)=CC=1C(=O)N(O)C(=O)C2=CC(Cl)=C3N1CCCC1 HVCIKRLEWIFUPO-UHFFFAOYSA-N 0.000 claims description 2
HRCMUWXKQHOULX-UHFFFAOYSA-N 5-fluoro-2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound FC1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CCCC1 HRCMUWXKQHOULX-UHFFFAOYSA-N 0.000 claims description 2
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
PISMCGHINLJCAB-UHFFFAOYSA-N 8-bromo-5-chloro-2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound ClC1=CC(=C23)C(=O)N(O)C(=O)C2=CC(Br)=CC3=C1N1CCCC1 PISMCGHINLJCAB-UHFFFAOYSA-N 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
238000010511 deprotection reaction Methods 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
SKBHZSLCDPEXBF-UHFFFAOYSA-N 11-hydroxy-4-(pyridin-2-ylmethyl)-6-oxa-4,11-diazatetracyclo[7.7.1.02,7.013,17]heptadeca-1(17),2(7),8,13,15-pentaene-10,12-dione Chemical compound C1OC2=CC(=C34)C(=O)N(O)C(=O)C3=CC=CC4=C2CN1CC1=CC=CC=N1 SKBHZSLCDPEXBF-UHFFFAOYSA-N 0.000 claims 1
OUOPXQSYZJBTMB-UHFFFAOYSA-N 2-hydroxy-5-methoxy-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound COC1=CC(=C23)C(=O)N(O)C(=O)C3=CC=CC2=C1N1CCCCC1 OUOPXQSYZJBTMB-UHFFFAOYSA-N 0.000 claims 1
FCIHRNHSIWJAJP-UHFFFAOYSA-N 6-(3-aminopyrrolidin-1-yl)-2-hydroxy-5-methoxybenzo[de]isoquinoline-1,3-dione Chemical compound COC1=CC(=C23)C(=O)N(O)C(=O)C3=CC=CC2=C1N1CCC(N)C1 FCIHRNHSIWJAJP-UHFFFAOYSA-N 0.000 claims 1
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 1
NOKUPYDPWYMPCL-QRPNPIFTSA-N C1CN(C[C@H]1N)C2=C(C=C3C4=C2C=CC=C4C(=O)N(C3=O)O)Br.Cl Chemical compound C1CN(C[C@H]1N)C2=C(C=C3C4=C2C=CC=C4C(=O)N(C3=O)O)Br.Cl NOKUPYDPWYMPCL-QRPNPIFTSA-N 0.000 claims 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 157
229910001868 water Inorganic materials 0.000 description 139
239000000243 solution Substances 0.000 description 125
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 124
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 116
239000000203 mixture Substances 0.000 description 112
239000007787 solid Substances 0.000 description 91
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 89
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 84
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 80
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
239000002244 precipitate Substances 0.000 description 62
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 58
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
238000005481 NMR spectroscopy Methods 0.000 description 52
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 41
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 41
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
239000000725 suspension Substances 0.000 description 37
239000011541 reaction mixture Substances 0.000 description 35
239000002904 solvent Substances 0.000 description 32
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 25
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 25
229960000583 acetic acid Drugs 0.000 description 25
229910017604 nitric acid Inorganic materials 0.000 description 25
239000005457 ice water Substances 0.000 description 23
238000001914 filtration Methods 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
239000000047 product Substances 0.000 description 20
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
239000002585 base Substances 0.000 description 18
238000005984 hydrogenation reaction Methods 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
238000003756 stirring Methods 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
238000010992 reflux Methods 0.000 description 16
229940086542 triethylamine Drugs 0.000 description 16
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 15
150000008064 anhydrides Chemical class 0.000 description 15
238000004440 column chromatography Methods 0.000 description 15
150000001412 amines Chemical class 0.000 description 14
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 14
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
239000003054 catalyst Substances 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
FKVNZFAMXGMPOU-UHFFFAOYSA-N 23204-36-6 Chemical compound C1=CC2=CC(O)=CC(C(=O)OC3=O)=C2C3=C1 FKVNZFAMXGMPOU-UHFFFAOYSA-N 0.000 description 9
239000002775 capsule Substances 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
239000000843 powder Substances 0.000 description 9
238000011282 treatment Methods 0.000 description 9
239000000706 filtrate Substances 0.000 description 8
IJVILRCYHDHVKF-UHFFFAOYSA-N 4-chloro-3-nitro-1,8-naphthalic anhydride Chemical compound C1=CC2=C(Cl)C([N+](=O)[O-])=CC(C(=O)OC3=O)=C2C3=C1 IJVILRCYHDHVKF-UHFFFAOYSA-N 0.000 description 7
IFTIXOTURKKYNL-UHFFFAOYSA-N 5-bromo-6-nitro-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C2=3)=CC=CC=3C([N+](=O)[O-])=C(Br)C=C2C(=O)N1OCC1=CC=CC=C1 IFTIXOTURKKYNL-UHFFFAOYSA-N 0.000 description 7
QIXHMCMCFSNKOG-UHFFFAOYSA-N 6492-86-0 Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3N QIXHMCMCFSNKOG-UHFFFAOYSA-N 0.000 description 7
239000012043 crude product Substances 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
238000000746 purification Methods 0.000 description 7
235000010288 sodium nitrite Nutrition 0.000 description 7
JUFBFZSMKMBCBO-UHFFFAOYSA-N st4132730 Chemical compound C1=CC2=CC(N)=CC(C(=O)OC3=O)=C2C3=C1 JUFBFZSMKMBCBO-UHFFFAOYSA-N 0.000 description 7
239000003826 tablet Substances 0.000 description 7
108020004414 DNA Proteins 0.000 description 6
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
XJHABGPPCLHLLV-UHFFFAOYSA-N benzo[de]isoquinoline-1,3-dione Chemical class C1=CC(C(=O)NC2=O)=C3C2=CC=CC3=C1 XJHABGPPCLHLLV-UHFFFAOYSA-N 0.000 description 6
239000000872 buffer Substances 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000003814 drug Substances 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000001632 sodium acetate Substances 0.000 description 6
235000017281 sodium acetate Nutrition 0.000 description 6
238000012360 testing method Methods 0.000 description 6
DYWWDZQRZYAPHQ-UHFFFAOYSA-N 3-benzoyl-4-ethyl-4-methyl-2-phenyl-1,3-oxazolidin-5-one Chemical compound O1C(=O)C(CC)(C)N(C(=O)C=2C=CC=CC=2)C1C1=CC=CC=C1 DYWWDZQRZYAPHQ-UHFFFAOYSA-N 0.000 description 5
AKFFBQJTSBSSMC-UHFFFAOYSA-N 6-chloro-1,3-dioxo-2-phenylmethoxybenzo[de]isoquinoline-5-carbonitrile Chemical compound O=C1C(C2=3)=CC=CC=3C(Cl)=C(C#N)C=C2C(=O)N1OCC1=CC=CC=C1 AKFFBQJTSBSSMC-UHFFFAOYSA-N 0.000 description 5
UGICDMDYJCXLHF-UHFFFAOYSA-N 7-bromo-8-nitro-3-oxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaene-2,4-dione Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC(Br)=C3[N+](=O)[O-] UGICDMDYJCXLHF-UHFFFAOYSA-N 0.000 description 5
108010041052 DNA Topoisomerase IV Proteins 0.000 description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
230000001476 alcoholic effect Effects 0.000 description 5
230000000844 anti-bacterial effect Effects 0.000 description 5
231100000433 cytotoxic Toxicity 0.000 description 5
230000001472 cytotoxic effect Effects 0.000 description 5
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000012039 electrophile Substances 0.000 description 5
238000006170 formylation reaction Methods 0.000 description 5
239000012458 free base Substances 0.000 description 5
230000002687 intercalation Effects 0.000 description 5
238000009830 intercalation Methods 0.000 description 5
239000000463 material Substances 0.000 description 5
LYXFXCSFCWZGNZ-UHFFFAOYSA-N 24050-49-5 Chemical compound C1=CC2=CC(Br)=CC(C(=O)OC3=O)=C2C3=C1 LYXFXCSFCWZGNZ-UHFFFAOYSA-N 0.000 description 4
DTUOTSLAFJCQHN-UHFFFAOYSA-N 4-bromo-1,8-naphthalic anhydride Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3Br DTUOTSLAFJCQHN-UHFFFAOYSA-N 0.000 description 4
LKOZHLXUWUBRDK-UHFFFAOYSA-N 4-nitro-1,8-naphthalic anhydride Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3[N+](=O)[O-] LKOZHLXUWUBRDK-UHFFFAOYSA-N 0.000 description 4
208000035143 Bacterial infection Diseases 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000000259 anti-tumor effect Effects 0.000 description 4
238000003556 assay Methods 0.000 description 4
208000022362 bacterial infectious disease Diseases 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000003480 eluent Substances 0.000 description 4
230000022244 formylation Effects 0.000 description 4
239000000499 gel Substances 0.000 description 4
150000008282 halocarbons Chemical class 0.000 description 4
HWJHZLJIIWOTGZ-UHFFFAOYSA-N n-(hydroxymethyl)acetamide Chemical compound CC(=O)NCO HWJHZLJIIWOTGZ-UHFFFAOYSA-N 0.000 description 4
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 4
ZBDXGNXNXXPKJI-UHFFFAOYSA-N o-tert-butylhydroxylamine;hydrochloride Chemical compound Cl.CC(C)(C)ON ZBDXGNXNXXPKJI-UHFFFAOYSA-N 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 4
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
YKAIOKLRGQWKFJ-UHFFFAOYSA-N (3-amino-4,5-dinitronaphthalene-1-carbonyl) 3-amino-4,5-dinitronaphthalene-1-carboxylate Chemical compound C1=CC=C([N+]([O-])=O)C2=C([N+]([O-])=O)C(N)=CC(C(=O)OC(=O)C=3C4=CC=CC(=C4C([N+]([O-])=O)=C(N)C=3)[N+]([O-])=O)=C21 YKAIOKLRGQWKFJ-UHFFFAOYSA-N 0.000 description 3
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
XPTRZSUEJCRSGK-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]-5-nitro-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=CC([N+]([O-])=O)=CC=1C(=O)N(OC(C)(C)C)C(=O)C2=CC=C3N1CCCC1 XPTRZSUEJCRSGK-UHFFFAOYSA-N 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
KTWCUGUUDHJVIH-UHFFFAOYSA-N 2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical class C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1 KTWCUGUUDHJVIH-UHFFFAOYSA-N 0.000 description 3
UJEUBSWHCGDJQU-UHFFFAOYSA-N 4-chloro-1,8-naphthalic anhydride Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3Cl UJEUBSWHCGDJQU-UHFFFAOYSA-N 0.000 description 3
CRROHOSEIDWQDZ-UHFFFAOYSA-N 5,6-dichloro-2-[(2-methylpropan-2-yl)oxy]-7-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound ClC1=CC(C(N(OC(C)(C)C)C2=O)=O)=C3C2=CC=C([N+]([O-])=O)C3=C1Cl CRROHOSEIDWQDZ-UHFFFAOYSA-N 0.000 description 3
UZZONNRADHHZJE-UHFFFAOYSA-N 5,6-dichloro-2-[(2-methylpropan-2-yl)oxy]benzo[de]isoquinoline-1,3-dione Chemical compound ClC1=CC(C(N(OC(C)(C)C)C2=O)=O)=C3C2=CC=CC3=C1Cl UZZONNRADHHZJE-UHFFFAOYSA-N 0.000 description 3
UPALIKSFLSVKIS-UHFFFAOYSA-N 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione Chemical compound NC1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 UPALIKSFLSVKIS-UHFFFAOYSA-N 0.000 description 3
OAIWZDIYONYZKE-UHFFFAOYSA-N 5-bromo-2-phenylmethoxy-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCCCC3)C(Br)=CC=2C(=O)N1OCC1=CC=CC=C1 OAIWZDIYONYZKE-UHFFFAOYSA-N 0.000 description 3
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
108010054814 DNA Gyrase Proteins 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
229920001917 Ficoll Polymers 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000011543 agarose gel Substances 0.000 description 3
150000004703 alkoxides Chemical class 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
230000001580 bacterial effect Effects 0.000 description 3
229910052796 boron Inorganic materials 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 3
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
229910000024 caesium carbonate Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 3
230000003013 cytotoxicity Effects 0.000 description 3
231100000135 cytotoxicity Toxicity 0.000 description 3
239000012954 diazonium Substances 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
229910052742 iron Inorganic materials 0.000 description 3
239000007788 liquid Substances 0.000 description 3
210000004962 mammalian cell Anatomy 0.000 description 3
238000006396 nitration reaction Methods 0.000 description 3
239000012038 nucleophile Substances 0.000 description 3
238000007344 nucleophilic reaction Methods 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
OAVVVDYRXPQNKC-UHFFFAOYSA-N (2-acetamido-4,5-dichloronaphthalene-1-carbonyl) 2-acetamido-4,5-dichloronaphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC(=O)C3=C4C=CC=C(Cl)C4=C(Cl)C=C3NC(=O)C)=C(NC(C)=O)C=C(Cl)C2=C1Cl OAVVVDYRXPQNKC-UHFFFAOYSA-N 0.000 description 2
QZDQOPMHBJXTKM-UHFFFAOYSA-N (5,8-diacetamido-1,3-dioxobenzo[de]isoquinolin-2-yl) acetate Chemical compound CC(=O)NC1=CC2=CC(NC(=O)C)=CC(C(=O)N(OC(C)=O)C3=O)=C2C3=C1 QZDQOPMHBJXTKM-UHFFFAOYSA-N 0.000 description 2
AKSGGFOOVGPRJK-UHFFFAOYSA-N 1,3-dioxo-2-phenylmethoxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-5-carbonitrile Chemical compound O=C1C(C=23)=CC(C#N)=C(N4CCCC4)C3=CC=CC=2C(=O)N1OCC1=CC=CC=C1 AKSGGFOOVGPRJK-UHFFFAOYSA-N 0.000 description 2
IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
FLNFSJVXMHHOMM-UHFFFAOYSA-N 2,5-dihydroxybenzo[de]isoquinoline-1,3-dione Chemical compound OC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1 FLNFSJVXMHHOMM-UHFFFAOYSA-N 0.000 description 2
GMEPBTSSPRJOPR-UHFFFAOYSA-N 2-(1,3-dioxo-2-phenylmethoxybenzo[de]isoquinolin-5-yl)oxyethyl acetate Chemical compound O=C1C(C=23)=CC=CC3=CC(OCCOC(=O)C)=CC=2C(=O)N1OCC1=CC=CC=C1 GMEPBTSSPRJOPR-UHFFFAOYSA-N 0.000 description 2
FAZBDSONYCMXBP-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]-5-nitro-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(=C23)C(=O)N(OC(C)(C)C)C(=O)C2=CC=CC3=C1N1CCCC1 FAZBDSONYCMXBP-UHFFFAOYSA-N 0.000 description 2
XXVLKDRPHSFIIB-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 XXVLKDRPHSFIIB-UHFFFAOYSA-N 0.000 description 2
JHWIEAWILPSRMU-UHFFFAOYSA-N 2-methyl-3-pyrimidin-4-ylpropanoic acid Chemical compound OC(=O)C(C)CC1=CC=NC=N1 JHWIEAWILPSRMU-UHFFFAOYSA-N 0.000 description 2
FNDHYAUUJZHCII-UHFFFAOYSA-N 2-phenylmethoxy-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=C(N4CCCCC4)C3=CC=CC=2C(=O)N1OCC1=CC=CC=C1 FNDHYAUUJZHCII-UHFFFAOYSA-N 0.000 description 2
IEOZHBABRCHNDS-UHFFFAOYSA-N 2-phenylmethoxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=C(N4CCCC4)C3=CC=CC=2C(=O)N1OCC1=CC=CC=C1 IEOZHBABRCHNDS-UHFFFAOYSA-N 0.000 description 2
RQPWAUODOJDARQ-UHFFFAOYSA-N 3-(1,3-dioxo-2-phenylmethoxybenzo[de]isoquinolin-5-yl)oxypropanoic acid Chemical compound O=C1C(C=23)=CC=CC3=CC(OCCC(=O)O)=CC=2C(=O)N1OCC1=CC=CC=C1 RQPWAUODOJDARQ-UHFFFAOYSA-N 0.000 description 2
BGCFKMKBKIBZNU-UHFFFAOYSA-N 3-methoxyacenaphthylene-1,2-dione Chemical compound C1=CC=C2C(=O)C(=O)C3=C2C1=CC=C3OC BGCFKMKBKIBZNU-UHFFFAOYSA-N 0.000 description 2
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical class C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 description 2
XHJLNUHOZBNWAX-UHFFFAOYSA-N 5,6-dichloro-1,2-dihydroacenaphthylen-3-amine Chemical compound ClC1=CC=C2CCC3=C2C1=C(Cl)C=C3N XHJLNUHOZBNWAX-UHFFFAOYSA-N 0.000 description 2
CPUYXVCRDMGHTM-UHFFFAOYSA-N 5,6-dichloro-2-[(2-methylpropan-2-yl)oxy]-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=C(Cl)C(Cl)=CC=1C(=O)N(OC(C)(C)C)C(=O)C2=CC=C3N1CCCC1 CPUYXVCRDMGHTM-UHFFFAOYSA-N 0.000 description 2
FKXQWQXZSZJWPH-UHFFFAOYSA-N 5,6-dichloro-2-[(2-methylpropan-2-yl)oxy]-8-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(OC(C)(C)C)C2=O)=O)=C3C2=CC(Cl)=C(Cl)C3=C1 FKXQWQXZSZJWPH-UHFFFAOYSA-N 0.000 description 2
LRSWRYPQVAPAFQ-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=CC(OCCN(C)C)=CC=2C(=O)N1OCC1=CC=CC=C1 LRSWRYPQVAPAFQ-UHFFFAOYSA-N 0.000 description 2
SAWLDYRYYCCJQA-UHFFFAOYSA-N 5-amino-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=CC(N)=CC(C(=O)N(O)C3=O)=C2C3=C1 SAWLDYRYYCCJQA-UHFFFAOYSA-N 0.000 description 2
MFJQEBOSABXTIH-UHFFFAOYSA-N 5-bromo-2-hydroxy-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=CC(Br)=CC=1C(=O)N(O)C(=O)C2=CC=C3N1CCCC1 MFJQEBOSABXTIH-UHFFFAOYSA-N 0.000 description 2
ICMZVZCNPVXWCH-UHFFFAOYSA-N 5-bromo-2-phenylmethoxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCCC3)C(Br)=CC=2C(=O)N1OCC1=CC=CC=C1 ICMZVZCNPVXWCH-UHFFFAOYSA-N 0.000 description 2
JBUVFKPTKKWWBZ-UHFFFAOYSA-N 5-bromo-2-phenylmethoxy-7-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=C(N4CCCCC4)C3=CC(Br)=CC=2C(=O)N1OCC1=CC=CC=C1 JBUVFKPTKKWWBZ-UHFFFAOYSA-N 0.000 description 2
MOQSDRRSEUVLDB-UHFFFAOYSA-N 5-bromo-6-(3-methylpiperidin-1-yl)-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound C1C(C)CCCN1C1=C(Br)C=C2C3=C1C=CC=C3C(=O)N(OCC=1C=CC=CC=1)C2=O MOQSDRRSEUVLDB-UHFFFAOYSA-N 0.000 description 2
WQOCCNQGHAUUKQ-UHFFFAOYSA-N 5-bromo-6-(dimethylamino)-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C2=3)=CC=CC=3C(N(C)C)=C(Br)C=C2C(=O)N1OCC1=CC=CC=C1 WQOCCNQGHAUUKQ-UHFFFAOYSA-N 0.000 description 2
UYLJPXJCFSAAEH-UHFFFAOYSA-N 5-bromo-7-nitro-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C2=3)=CC(Br)=CC=3C([N+](=O)[O-])=CC=C2C(=O)N1OCC1=CC=CC=C1 UYLJPXJCFSAAEH-UHFFFAOYSA-N 0.000 description 2
JETSBZHCYVGCMM-UHFFFAOYSA-N 5-chloro-2-[(2-methylpropan-2-yl)oxy]-8-nitro-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=CC([N+]([O-])=O)=CC=1C(=O)N(OC(C)(C)C)C(=O)C2=CC(Cl)=C3N1CCCC1 JETSBZHCYVGCMM-UHFFFAOYSA-N 0.000 description 2
MTVAXQRAVYSHND-UHFFFAOYSA-N 5-fluoro-6-methoxy-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C2=3)=CC=CC=3C(OC)=C(F)C=C2C(=O)N1OCC1=CC=CC=C1 MTVAXQRAVYSHND-UHFFFAOYSA-N 0.000 description 2
OKBGAWQOEAAYDH-UHFFFAOYSA-N 5-hydroxy-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=CC(O)=CC=2C(=O)N1OCC1=CC=CC=C1 OKBGAWQOEAAYDH-UHFFFAOYSA-N 0.000 description 2
UKKDPCVOPKLLAM-UHFFFAOYSA-N 5-hydroxy-6-nitro-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C([N+]([O-])=O)C(O)=CC=2C(=O)N1OCC1=CC=CC=C1 UKKDPCVOPKLLAM-UHFFFAOYSA-N 0.000 description 2
IQGJHHFWQZQEHD-UHFFFAOYSA-N 5-methoxy-2-phenylmethoxy-6-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCCCC3)C(OC)=CC=2C(=O)N1OCC1=CC=CC=C1 IQGJHHFWQZQEHD-UHFFFAOYSA-N 0.000 description 2
IDIIIMVUTAYCEJ-UHFFFAOYSA-N 5-methoxy-2-phenylmethoxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCCC3)C(OC)=CC=2C(=O)N1OCC1=CC=CC=C1 IDIIIMVUTAYCEJ-UHFFFAOYSA-N 0.000 description 2
CYPNKRGMOWNFCI-UHFFFAOYSA-N 5-methoxy-6-(4-methylpiperazin-1-yl)-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCN(C)CC3)C(OC)=CC=2C(=O)N1OCC1=CC=CC=C1 CYPNKRGMOWNFCI-UHFFFAOYSA-N 0.000 description 2
CXHWUBYJXJJHJV-UHFFFAOYSA-N 5-methoxy-6-morpholin-4-yl-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCOCC3)C(OC)=CC=2C(=O)N1OCC1=CC=CC=C1 CXHWUBYJXJJHJV-UHFFFAOYSA-N 0.000 description 2
JIODDZXYPAMYSP-UHFFFAOYSA-N 5-methoxy-6-nitro-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C([N+]([O-])=O)C(OC)=CC=2C(=O)N1OCC1=CC=CC=C1 JIODDZXYPAMYSP-UHFFFAOYSA-N 0.000 description 2
UBOBAHYVXMNCJB-UHFFFAOYSA-N 5-methyl-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=CC(C)=CC=2C(=O)N1OCC1=CC=CC=C1 UBOBAHYVXMNCJB-UHFFFAOYSA-N 0.000 description 2
BFKXHILYGIQGCB-UHFFFAOYSA-N 52083-08-6 Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3O BFKXHILYGIQGCB-UHFFFAOYSA-N 0.000 description 2
KKJWSPNYCIBOTM-UHFFFAOYSA-N 6-(3-aminopyrrolidin-1-yl)-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1C(N)CCN1C1=CC=C2C3=C1C=CC=C3C(=O)N(O)C2=O KKJWSPNYCIBOTM-UHFFFAOYSA-N 0.000 description 2
YHZVOJLFEPAJOY-PPHPATTJSA-N 6-[(3S)-3-aminopyrrolidin-1-yl]-2-hydroxy-1,3-dioxobenzo[de]isoquinoline-5-carbonitrile hydrochloride Chemical compound Cl.N[C@H]1CCN(C1)c1c(cc2C(=O)N(O)C(=O)c3cccc1c23)C#N YHZVOJLFEPAJOY-PPHPATTJSA-N 0.000 description 2
WHNJATCBDPXIMC-QMMMGPOBSA-N 6-[(3s)-3-aminopyrrolidin-1-yl]-5-bromo-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1[C@@H](N)CCN1C1=C(Br)C=C2C3=C1C=CC=C3C(=O)N(O)C2=O WHNJATCBDPXIMC-QMMMGPOBSA-N 0.000 description 2
BDWSVPHGKIUKPC-UHFFFAOYSA-N 6-bromo-2,5-dihydroxybenzo[de]isoquinoline-1,3-dione Chemical compound OC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1Br BDWSVPHGKIUKPC-UHFFFAOYSA-N 0.000 description 2
SMFFDONWMCQXFW-UHFFFAOYSA-N 6-bromo-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1Br SMFFDONWMCQXFW-UHFFFAOYSA-N 0.000 description 2
BYWPYMWPZSOLNV-UHFFFAOYSA-N 6-bromo-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C2=3)=CC=CC=3C(Br)=CC=C2C(=O)N1OCC1=CC=CC=C1 BYWPYMWPZSOLNV-UHFFFAOYSA-N 0.000 description 2
QMBNPVJDQCTDAY-UHFFFAOYSA-N 6-bromo-5-methoxy-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(Br)C(OC)=CC=2C(=O)N1OCC1=CC=CC=C1 QMBNPVJDQCTDAY-UHFFFAOYSA-N 0.000 description 2
WLAMMQMQMXIFJT-UHFFFAOYSA-N 6-chloro-2-[(2-methylpropan-2-yl)oxy]-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(OC(C)(C)C)C2=O)=O)=C3C2=CC=CC3=C1Cl WLAMMQMQMXIFJT-UHFFFAOYSA-N 0.000 description 2
XSUJDXXLKIWCEL-UHFFFAOYSA-N 6-methoxy-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C2=3)=CC=CC=3C(OC)=CC=C2C(=O)N1OCC1=CC=CC=C1 XSUJDXXLKIWCEL-UHFFFAOYSA-N 0.000 description 2
RQFZBFXVRGFMMX-UHFFFAOYSA-N 6-morpholin-4-yl-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=C(N4CCOCC4)C3=CC=CC=2C(=O)N1OCC1=CC=CC=C1 RQFZBFXVRGFMMX-UHFFFAOYSA-N 0.000 description 2
PYDGAZDULXZGAC-UHFFFAOYSA-N 7-chloro-2-[(2-methylpropan-2-yl)oxy]-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(OC(C)(C)C)C2=O)=O)=C3C2=CC=C(Cl)C3=C1 PYDGAZDULXZGAC-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
108020000946 Bacterial DNA Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
108090000323 DNA Topoisomerases Proteins 0.000 description 2
102000003915 DNA Topoisomerases Human genes 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
108010067770 Endopeptidase K Proteins 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
GRSMWKLPSNHDHA-UHFFFAOYSA-N Naphthalic anhydride Chemical class C1=CC(C(=O)OC2=O)=C3C2=CC=CC3=C1 GRSMWKLPSNHDHA-UHFFFAOYSA-N 0.000 description 2
WKFPHNKOIXLMLC-UHFFFAOYSA-N O=C1N(C(C)(C)C)C(=O)C2=C(O[SiH3])C(N)=C(C)C3=C2C1=CC(N)=C3C Chemical compound O=C1N(C(C)(C)C)C(=O)C2=C(O[SiH3])C(N)=C(C)C3=C2C1=CC(N)=C3C WKFPHNKOIXLMLC-UHFFFAOYSA-N 0.000 description 2
240000007594 Oryza sativa Species 0.000 description 2
235000007164 Oryza sativa Nutrition 0.000 description 2
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
AWKPHASCYSPWCI-JTQLQIEISA-N [(3s)-1-(5-cyano-2-hydroxy-1,3-dioxobenzo[de]isoquinolin-6-yl)pyrrolidin-3-yl]carbamic acid Chemical compound N#CC1=CC(=C23)C(=O)N(O)C(=O)C2=CC=CC3=C1N1CC[C@H](NC(O)=O)C1 AWKPHASCYSPWCI-JTQLQIEISA-N 0.000 description 2
UXZMLECYBHANRH-UHFFFAOYSA-K [B+3].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F Chemical compound [B+3].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F UXZMLECYBHANRH-UHFFFAOYSA-K 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 2
229960004701 amonafide Drugs 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
230000008901 benefit Effects 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
CWBHKBKGKCDGDM-UHFFFAOYSA-N bis[(2,2,2-trifluoroacetyl)oxy]boranyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OB(OC(=O)C(F)(F)F)OC(=O)C(F)(F)F CWBHKBKGKCDGDM-UHFFFAOYSA-N 0.000 description 2
JNQPQEHGPXDQTA-UHFFFAOYSA-N boric acid;2,2,2-trifluoroacetic acid Chemical compound OB(O)O.OC(=O)C(F)(F)F JNQPQEHGPXDQTA-UHFFFAOYSA-N 0.000 description 2
239000012267 brine Substances 0.000 description 2
JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
230000005757 colony formation Effects 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
239000008367 deionised water Substances 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
150000004985 diamines Chemical class 0.000 description 2
AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 2
229910000397 disodium phosphate Inorganic materials 0.000 description 2
PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 description 2
238000007350 electrophilic reaction Methods 0.000 description 2
238000001962 electrophoresis Methods 0.000 description 2
ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
229960005542 ethidium bromide Drugs 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
238000007429 general method Methods 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
150000002739 metals Chemical class 0.000 description 2
KPQJSSLKKBKWEW-RKDOVGOJSA-N methanesulfonic acid;5-nitro-2-[(2r)-1-[2-[[(2r)-2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propyl]amino]ethylamino]propan-2-yl]benzo[de]isoquinoline-1,3-dione Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.[O-][N+](=O)C1=CC(C(N([C@@H](CNCCNC[C@@H](C)N2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 KPQJSSLKKBKWEW-RKDOVGOJSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
229950001745 mitonafide Drugs 0.000 description 2
DCYCBHAARZGTLE-UHFFFAOYSA-N n-(2-hydroxy-1,3-dioxo-6-pyrrolidin-1-ylbenzo[de]isoquinolin-5-yl)acetamide Chemical compound CC(=O)NC1=CC(=C23)C(=O)N(O)C(=O)C3=CC=CC2=C1N1CCCC1 DCYCBHAARZGTLE-UHFFFAOYSA-N 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
VYCHJEXJHFTAQI-UHFFFAOYSA-N o-prop-2-enylhydroxylamine;hydrate;hydrochloride Chemical compound O.Cl.NOCC=C VYCHJEXJHFTAQI-UHFFFAOYSA-N 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
239000013612 plasmid Substances 0.000 description 2
239000011698 potassium fluoride Substances 0.000 description 2
235000003270 potassium fluoride Nutrition 0.000 description 2
235000009566 rice Nutrition 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
235000011150 stannous chloride Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 2
DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
FJYNQCQYFKUHFB-UHFFFAOYSA-N (2-hydroxy-1,3-dioxobenzo[de]isoquinolin-5-yl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1 FJYNQCQYFKUHFB-UHFFFAOYSA-N 0.000 description 1
FHIMETDUFUEOOJ-UHFFFAOYSA-N (5-acetamido-1,3-dioxobenzo[de]isoquinolin-2-yl) acetate Chemical compound C1=CC2=CC(NC(=O)C)=CC(C(=O)N(OC(C)=O)C3=O)=C2C3=C1 FHIMETDUFUEOOJ-UHFFFAOYSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
JLHMJWHSBYZWJJ-UHFFFAOYSA-N 1,2-thiazole 1-oxide Chemical compound O=S1C=CC=N1 JLHMJWHSBYZWJJ-UHFFFAOYSA-N 0.000 description 1
DNGBUPUFHJKWGM-UHFFFAOYSA-N 1,3-dioxo-2-phenylmethoxy-6-piperidin-1-ylbenzo[de]isoquinoline-5-carbonitrile Chemical compound O=C1C(C=23)=CC(C#N)=C(N4CCCCC4)C3=CC=CC=2C(=O)N1OCC1=CC=CC=C1 DNGBUPUFHJKWGM-UHFFFAOYSA-N 0.000 description 1
XYMJPWIZLGKEEO-UHFFFAOYSA-N 1-(1,2-dihydroacenaphthylen-3-yl)ethanone Chemical compound C1=CC=C2CCC3=C2C1=CC=C3C(=O)C XYMJPWIZLGKEEO-UHFFFAOYSA-N 0.000 description 1
CCQJLRYBHHEKMZ-UHFFFAOYSA-N 11-hydroxy-3-methoxy-4,6-dioxa-11-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(17),2(7),8,13,15-pentaene-10,12-dione Chemical compound C1=CC2=C3C(OC)OCOC3=CC(C(=O)N(O)C3=O)=C2C3=C1 CCQJLRYBHHEKMZ-UHFFFAOYSA-N 0.000 description 1
XRACJBOQFPQWGZ-UHFFFAOYSA-N 11-methoxy-5,8,10-trioxabenzo[de]anthracene-4,6-dione Chemical compound C1=CC2=C3C(OC)OCOC3=CC(C(=O)OC3=O)=C2C3=C1 XRACJBOQFPQWGZ-UHFFFAOYSA-N 0.000 description 1
DHBHLWCPPPYANX-UHFFFAOYSA-N 2,5-dihydroxy-1,3-dioxobenzo[de]isoquinoline-6-carbaldehyde Chemical compound OC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1C=O DHBHLWCPPPYANX-UHFFFAOYSA-N 0.000 description 1
NQRWWXDOJDSYLY-UHFFFAOYSA-N 2,5-dihydroxy-6-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound OC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1[N+]([O-])=O NQRWWXDOJDSYLY-UHFFFAOYSA-N 0.000 description 1
VEPZQLPLWGCNRM-UHFFFAOYSA-N 2-(2-hydroxy-1,3-dioxobenzo[de]isoquinolin-5-yl)oxyethyl acetate Chemical compound C1=CC2=CC(OCCOC(=O)C)=CC(C(=O)N(O)C3=O)=C2C3=C1 VEPZQLPLWGCNRM-UHFFFAOYSA-N 0.000 description 1
LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 1
IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 1
BCBJMWZHCLVRCS-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-5,8-dinitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC([N+]([O-])=O)=CC3=C1 BCBJMWZHCLVRCS-UHFFFAOYSA-N 0.000 description 1
OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 1
RGHQKFQZGLKBCF-UHFFFAOYSA-N 2-bromoethyl acetate Chemical compound CC(=O)OCCBr RGHQKFQZGLKBCF-UHFFFAOYSA-N 0.000 description 1
MONMFXREYOKQTI-UHFFFAOYSA-N 2-bromopropanoic acid Chemical compound CC(Br)C(O)=O MONMFXREYOKQTI-UHFFFAOYSA-N 0.000 description 1
VBGBCDYFHYZPTP-UHFFFAOYSA-N 2-chloro-n-(2,5-dihydroxy-4-methyl-1,3-dioxobenzo[de]isoquinolin-6-yl)acetamide Chemical compound C1=CC=C2C(=O)N(O)C(=O)C3=C2C1=C(NC(=O)CCl)C(O)=C3C VBGBCDYFHYZPTP-UHFFFAOYSA-N 0.000 description 1
TXNSZCSYBXHETP-UHFFFAOYSA-N 2-chloro-n-(hydroxymethyl)acetamide Chemical compound OCNC(=O)CCl TXNSZCSYBXHETP-UHFFFAOYSA-N 0.000 description 1
UOHAVHCCJOYZJS-UHFFFAOYSA-N 2-hydroxy-5,6-dimethoxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C(OC)C(OC)=CC(C(=O)N(O)C3=O)=C2C3=C1 UOHAVHCCJOYZJS-UHFFFAOYSA-N 0.000 description 1
CVSFMVRKGIWMIM-UHFFFAOYSA-N 2-hydroxy-5,8-dinitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(O)C2=O)=O)=C3C2=CC([N+]([O-])=O)=CC3=C1 CVSFMVRKGIWMIM-UHFFFAOYSA-N 0.000 description 1
AMHAKEDXIOVXPP-UHFFFAOYSA-N 2-hydroxy-5-(2-hydroxyethoxy)benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=CC(OCCO)=CC(C(=O)N(O)C3=O)=C2C3=C1 AMHAKEDXIOVXPP-UHFFFAOYSA-N 0.000 description 1
FWTUCJSQMYTMDI-UHFFFAOYSA-N 2-hydroxy-5-methoxy-6-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C([N+]([O-])=O)C(OC)=CC(C(=O)N(O)C3=O)=C2C3=C1 FWTUCJSQMYTMDI-UHFFFAOYSA-N 0.000 description 1
PELGTYIRGBFQRF-UHFFFAOYSA-N 2-hydroxy-5-methoxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=CC(OC)=CC(C(=O)N(O)C3=O)=C2C3=C1 PELGTYIRGBFQRF-UHFFFAOYSA-N 0.000 description 1
UBJZIVNRQNIZBP-UHFFFAOYSA-N 2-hydroxy-5-methyl-7-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=2C3=CC(C)=CC=2C(=O)N(O)C(=O)C1=CC=C3N1CCCC1 UBJZIVNRQNIZBP-UHFFFAOYSA-N 0.000 description 1
ATXRCJZCEGPIIO-UHFFFAOYSA-N 2-hydroxy-5-methylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=CC(C)=CC(C(=O)N(O)C3=O)=C2C3=C1 ATXRCJZCEGPIIO-UHFFFAOYSA-N 0.000 description 1
MGWVYQDKZKNRAZ-UHFFFAOYSA-N 2-hydroxy-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1 MGWVYQDKZKNRAZ-UHFFFAOYSA-N 0.000 description 1
FTNJHSOZBLANHY-UHFFFAOYSA-N 2-hydroxy-6,7-dinitrobenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(N(O)C2=O)=O)=C3C2=CC=C([N+]([O-])=O)C3=C1[N+]([O-])=O FTNJHSOZBLANHY-UHFFFAOYSA-N 0.000 description 1
JNZJPCRGQNFNFC-UHFFFAOYSA-N 2-hydroxy-6-methoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1N(O)C(=O)C2=CC=CC3=C2C1=CC=C3OC JNZJPCRGQNFNFC-UHFFFAOYSA-N 0.000 description 1
VEABBDUXRVQIQY-UHFFFAOYSA-N 2-hydroxy-6-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1[N+]([O-])=O VEABBDUXRVQIQY-UHFFFAOYSA-N 0.000 description 1
HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
MEPIVFDZIUCOHZ-UHFFFAOYSA-N 3-(2-hydroxy-1,3-dioxobenzo[de]isoquinolin-5-yl)oxypropanoic acid Chemical compound OC(=O)CCOC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1 MEPIVFDZIUCOHZ-UHFFFAOYSA-N 0.000 description 1
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
YUYWNOZHKNDSGZ-UHFFFAOYSA-N 3-hydroxy-11,13-dioxa-3-azatetracyclo[7.6.1.05,16.010,14]hexadeca-1(15),5,7,9(16),10(14)-pentaene-2,4-dione Chemical compound C=1C(C(N(O)C2=O)=O)=C3C2=CC=CC3=C2OCOC2=1 YUYWNOZHKNDSGZ-UHFFFAOYSA-N 0.000 description 1
BWRWNUQAQPAYCK-UHFFFAOYSA-N 3-methoxypyrrolidine Chemical compound COC1CCNC1 BWRWNUQAQPAYCK-UHFFFAOYSA-N 0.000 description 1
JEGMWWXJUXDNJN-UHFFFAOYSA-N 3-methylpiperidine Chemical compound CC1CCCNC1 JEGMWWXJUXDNJN-UHFFFAOYSA-N 0.000 description 1
KHZUQMIDLQGZQS-UHFFFAOYSA-N 4,7-dichloro-2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=C(Cl)C(=C23)C(=O)N(O)C(=O)C2=CC=C(Cl)C3=C1N1CCCC1 KHZUQMIDLQGZQS-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
MTGUPWGHQLICHN-UHFFFAOYSA-N 4-amino-7-chloro-2-hydroxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C=3C(Cl)=CC=C2C(=O)N(O)C(=O)C=1C(N)=CC=3N1CCCC1 MTGUPWGHQLICHN-UHFFFAOYSA-N 0.000 description 1
BTOJSYRZQZOMOK-UHFFFAOYSA-N 4-chloro-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=NC(Cl)=C2C=C1 BTOJSYRZQZOMOK-UHFFFAOYSA-N 0.000 description 1
WOHXJVJXAWXEQP-UHFFFAOYSA-M 4-sulfo-1,8-naphthalic anhydride potassium salt Chemical compound [K+].O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3S(=O)(=O)[O-] WOHXJVJXAWXEQP-UHFFFAOYSA-M 0.000 description 1
QQTNONSQLWTQPU-UHFFFAOYSA-N 5,6-dichloro-1,2-dihydroacenaphthylene Chemical compound C1CC2=CC=C(Cl)C3=C2C1=CC=C3Cl QQTNONSQLWTQPU-UHFFFAOYSA-N 0.000 description 1
IOMNJJNXTHXKQW-UHFFFAOYSA-N 5,6-dichloro-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound ClC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1Cl IOMNJJNXTHXKQW-UHFFFAOYSA-N 0.000 description 1
VYSXKWFMXPTHFI-UHFFFAOYSA-N 5,6-dichloro-3-nitro-1,2-dihydroacenaphthylene Chemical compound ClC1=CC=C2CCC3=C2C1=C(Cl)C=C3[N+](=O)[O-] VYSXKWFMXPTHFI-UHFFFAOYSA-N 0.000 description 1
AUXIZWMEWCYSOY-UHFFFAOYSA-N 5-amino-6-chloro-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C(Cl)C(N)=CC(C(=O)N(O)C3=O)=C2C3=C1 AUXIZWMEWCYSOY-UHFFFAOYSA-N 0.000 description 1
RDSJFEOTHXEZDF-UHFFFAOYSA-N 5-amino-6-chloro-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(Cl)C(N)=CC=2C(=O)N1OCC1=CC=CC=C1 RDSJFEOTHXEZDF-UHFFFAOYSA-N 0.000 description 1
NCWRGQQXWJPRJB-UHFFFAOYSA-N 5-bromo-2-hydroxy-6,7-dinitrobenzo[de]isoquinoline-1,3-dione Chemical compound BrC1=CC(C(N(O)C2=O)=O)=C3C2=CC=C([N+]([O-])=O)C3=C1[N+]([O-])=O NCWRGQQXWJPRJB-UHFFFAOYSA-N 0.000 description 1
IIOHXGNOBHHJNA-UHFFFAOYSA-N 5-bromo-2-hydroxy-6-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound BrC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1[N+]([O-])=O IIOHXGNOBHHJNA-UHFFFAOYSA-N 0.000 description 1
XBTRBEVEYVQQBE-UHFFFAOYSA-N 5-bromo-2-hydroxy-7-piperidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound C=12C3=CC(Br)=CC=1C(=O)N(O)C(=O)C2=CC=C3N1CCCCC1 XBTRBEVEYVQQBE-UHFFFAOYSA-N 0.000 description 1
NNTXCWBGCQPPBP-UHFFFAOYSA-N 5-bromo-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=CC(Br)=CC=2C(=O)N1OCC1=CC=CC=C1 NNTXCWBGCQPPBP-UHFFFAOYSA-N 0.000 description 1
KBLDWGWNRUDDIA-UHFFFAOYSA-N 5-chloro-6-(3-methoxypyrrolidin-1-yl)-2-[(2-methylpropan-2-yl)oxy]benzo[de]isoquinoline-1,3-dione Chemical compound C1C(OC)CCN1C1=C(Cl)C=C2C3=C1C=CC=C3C(=O)N(OC(C)(C)C)C2=O KBLDWGWNRUDDIA-UHFFFAOYSA-N 0.000 description 1
OFYLZNSAHHQATI-UHFFFAOYSA-N 5-ethoxy-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=CC(OCC)=CC(C(=O)N(O)C3=O)=C2C3=C1 OFYLZNSAHHQATI-UHFFFAOYSA-N 0.000 description 1
LLUBZQYTUUBARU-UHFFFAOYSA-N 5-fluoro-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound FC1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1 LLUBZQYTUUBARU-UHFFFAOYSA-N 0.000 description 1
OCLIARLCRIQQBQ-UHFFFAOYSA-N 5-fluoro-2-phenylmethoxy-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(N3CCCC3)C(F)=CC=2C(=O)N1OCC1=CC=CC=C1 OCLIARLCRIQQBQ-UHFFFAOYSA-N 0.000 description 1
IFIXLQRZEKLAIY-UHFFFAOYSA-N 5-hydroxy-10-methyl-9,10-dihydro-8-oxa-5,10-diaza-cyclopenta[a]phenalene-4,6-dione Chemical compound C1=CC2=C3N(C)COC3=CC(C(=O)N(O)C3=O)=C2C3=C1 IFIXLQRZEKLAIY-UHFFFAOYSA-N 0.000 description 1
CAFWXODFGJCSDH-UHFFFAOYSA-N 5-hydroxy-11h-8,10-dioxa-5-aza-benzo[de]anthracene-4,6-dione Chemical compound C1OCOC2=CC(C(N(O)C3=O)=O)=C4C3=CC=CC4=C21 CAFWXODFGJCSDH-UHFFFAOYSA-N 0.000 description 1
PDPRQXXUQOWCPF-UHFFFAOYSA-N 5-hydroxy-8h-9,11-dioxa-5-aza-benzo[de]anthracene-4,6-dione Chemical compound O1COCC2=CC(C(N(O)C3=O)=O)=C4C3=CC=CC4=C21 PDPRQXXUQOWCPF-UHFFFAOYSA-N 0.000 description 1
PVPKPHIRECCUNI-UHFFFAOYSA-N 5-hydroxy-9-methyl-10h-5,8,10-triaza-cyclopenta[a]phenalene-4,6-dione Chemical compound O=C1N(O)C(=O)C2=CC=CC3=C2C1=CC1=C3N=C(C)N1 PVPKPHIRECCUNI-UHFFFAOYSA-N 0.000 description 1
QFTYHZUVEZAPBC-UHFFFAOYSA-N 5-hydroxy-9h,10h-8,11-dioxa-5-aza-benzo[de]anthracene-4,6-dione Chemical compound O1CCOC2=CC(C(N(O)C3=O)=O)=C4C3=CC=CC4=C21 QFTYHZUVEZAPBC-UHFFFAOYSA-N 0.000 description 1
PMUGRQGOAFXTCW-UHFFFAOYSA-N 5-nitro-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=CC([N+](=O)[O-])=CC=2C(=O)N1OCC1=CC=CC=C1 PMUGRQGOAFXTCW-UHFFFAOYSA-N 0.000 description 1
XFASXEXSGWMZBR-UHFFFAOYSA-N 6,8-dibromo-2-hydroxy-5-methylbenzo[de]isoquinoline-1,3-dione Chemical compound BrC1=CC2=C(Br)C(C)=CC(C(=O)N(O)C3=O)=C2C3=C1 XFASXEXSGWMZBR-UHFFFAOYSA-N 0.000 description 1
MRYXDAZJSFGNLG-UHFFFAOYSA-N 6-(aminomethyl)-2-hydroxy-5-methoxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C(CN)C(OC)=CC(C(=O)N(O)C3=O)=C2C3=C1 MRYXDAZJSFGNLG-UHFFFAOYSA-N 0.000 description 1
WTVUQRJKNNMZHN-FJXQXJEOSA-N 6-[(3s)-3-aminopyrrolidin-1-yl]-4,7-dichloro-2-hydroxybenzo[de]isoquinoline-1,3-dione;hydrochloride Chemical compound Cl.C1[C@@H](N)CCN1C1=CC(Cl)=C2C3=C1C(Cl)=CC=C3C(=O)N(O)C2=O WTVUQRJKNNMZHN-FJXQXJEOSA-N 0.000 description 1
ZPLKWMVWIHZRQZ-UHFFFAOYSA-N 6-amino-2-hydroxy-5-methoxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C(N)C(OC)=CC(C(=O)N(O)C3=O)=C2C3=C1 ZPLKWMVWIHZRQZ-UHFFFAOYSA-N 0.000 description 1
ONKKYCZQTHLVLR-UHFFFAOYSA-N 6-amino-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1N(O)C(=O)C2=CC=CC3=C2C1=CC=C3N ONKKYCZQTHLVLR-UHFFFAOYSA-N 0.000 description 1
HBKIQWXCGKBBHI-UHFFFAOYSA-N 6-amino-5-bromo-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1N(O)C(=O)C2=CC=CC3=C2C1=CC(Br)=C3N HBKIQWXCGKBBHI-UHFFFAOYSA-N 0.000 description 1
IXMCQBAXWDLRMH-UHFFFAOYSA-N 6-amino-5-chloro-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1N(O)C(=O)C2=CC=CC3=C2C1=CC(Cl)=C3N IXMCQBAXWDLRMH-UHFFFAOYSA-N 0.000 description 1
KRHDAUKCDISJRD-UHFFFAOYSA-N 6-bromo-2-[(2-methylpropan-2-yl)oxy]benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(N(OC(C)(C)C)C2=O)=O)=C3C2=CC=CC3=C1Br KRHDAUKCDISJRD-UHFFFAOYSA-N 0.000 description 1
ZXBFHZQJLOTQMX-UHFFFAOYSA-N 6-bromo-2-hydroxy-5-methylbenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C(Br)C(C)=CC(C(=O)N(O)C3=O)=C2C3=C1 ZXBFHZQJLOTQMX-UHFFFAOYSA-N 0.000 description 1
PJGHLBGEWNZISB-UHFFFAOYSA-N 6-bromo-5-hydroxy-2-phenylmethoxybenzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=C(Br)C(O)=CC=2C(=O)N1OCC1=CC=CC=C1 PJGHLBGEWNZISB-UHFFFAOYSA-N 0.000 description 1
XNMFZQYOFQTAKK-UHFFFAOYSA-N 6-bromo-5-methoxy-2-[(2-methylpropan-2-yl)oxy]benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC2=C(Br)C(OC)=CC(C(=O)N(OC(C)(C)C)C3=O)=C2C3=C1 XNMFZQYOFQTAKK-UHFFFAOYSA-N 0.000 description 1
NWYOXTXLCOKUMR-UHFFFAOYSA-N 6-chloro-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1Cl NWYOXTXLCOKUMR-UHFFFAOYSA-N 0.000 description 1
REQJYLGCTCYFMQ-UHFFFAOYSA-N 6-fluoro-2-hydroxybenzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1F REQJYLGCTCYFMQ-UHFFFAOYSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
LFOGXNUWGZDJMA-UHFFFAOYSA-N 8-bromo-5-chloro-6-pyrrolidin-1-ylbenzo[de]isoquinoline-1,3-dione Chemical compound ClC1=CC(=C23)C(=O)NC(=O)C3=CC(Br)=CC2=C1N1CCCC1 LFOGXNUWGZDJMA-UHFFFAOYSA-N 0.000 description 1
ZUNRHNSMTAOKTE-UHFFFAOYSA-N 8h-5,9,11-trioxabenzo[de]anthracene-4,6-dione Chemical compound C12=CC=CC(C(=O)OC3=O)=C2C3=CC2=C1OCOC2 ZUNRHNSMTAOKTE-UHFFFAOYSA-N 0.000 description 1
YGROXRVJADPXSK-UHFFFAOYSA-N 9h,10h-5,8,11-trioxabenzo[de]anthracene-4,6-dione Chemical compound C12=CC=CC(C(=O)OC3=O)=C2C3=CC2=C1OCCO2 YGROXRVJADPXSK-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
FQYDLTOIDIRBJG-UHFFFAOYSA-N Cl.C(C1=CC=CC=C1)ON.C(C1=CC=CC=C1)ON1C(C2=CC=CC=3C2=C(C1=O)C=CC3Br)=O Chemical compound Cl.C(C1=CC=CC=C1)ON.C(C1=CC=CC=C1)ON1C(C2=CC=CC=3C2=C(C1=O)C=CC3Br)=O FQYDLTOIDIRBJG-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010022998 Irritability Diseases 0.000 description 1
108020003631 Kinetoplast DNA Proteins 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000907681 Morpho Species 0.000 description 1
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
206010034133 Pathogen resistance Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
239000008049 TAE buffer Substances 0.000 description 1
239000008051 TBE buffer Substances 0.000 description 1
239000004809 Teflon Substances 0.000 description 1
229920006362 Teflon® Polymers 0.000 description 1
229910003074 TiCl4 Inorganic materials 0.000 description 1
101710183280 Topoisomerase Proteins 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
206010052428 Wound Diseases 0.000 description 1
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
VRMDEGCCFZDMSC-HNNXBMFYSA-N [(3s)-1-(5-bromo-1,3-dioxo-2-phenylmethoxybenzo[de]isoquinolin-6-yl)pyrrolidin-3-yl]carbamic acid Chemical compound C1[C@@H](NC(=O)O)CCN1C1=C(Br)C=C2C3=C1C=CC=C3C(=O)N(OCC=1C=CC=CC=1)C2=O VRMDEGCCFZDMSC-HNNXBMFYSA-N 0.000 description 1
150000001239 acenaphthenes Chemical class 0.000 description 1
HGEVZDLYZYVYHD-UHFFFAOYSA-N acetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound CC(O)=O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O HGEVZDLYZYVYHD-UHFFFAOYSA-N 0.000 description 1
239000000654 additive Substances 0.000 description 1
125000006241 alcohol protecting group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000002141 anti-parasite Effects 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
235000021028 berry Nutrition 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000007844 bleaching agent Substances 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
244000309466 calf Species 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000030833 cell death Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000008395 clarifying agent Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
238000002784 cytotoxicity assay Methods 0.000 description 1
231100000263 cytotoxicity test Toxicity 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
229910000071 diazene Inorganic materials 0.000 description 1
150000001989 diazonium salts Chemical class 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
125000005594 diketone group Chemical group 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
WDRWZVWLVBXVOI-QTNFYWBSSA-L dipotassium;(2s)-2-aminopentanedioate Chemical compound [K+].[K+].[O-]C(=O)[C@@H](N)CCC([O-])=O WDRWZVWLVBXVOI-QTNFYWBSSA-L 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
125000006575 electron-withdrawing group Chemical group 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
HFTNNOZFRQLFQB-UHFFFAOYSA-N ethenoxy(trimethyl)silane Chemical compound C[Si](C)(C)OC=C HFTNNOZFRQLFQB-UHFFFAOYSA-N 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000000835 fiber Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000002363 herbicidal effect Effects 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
UANDWKVBMWTMJE-UHFFFAOYSA-N hydroxylamine 2-hydroxy-5-nitrobenzo[de]isoquinoline-1,3-dione hydrochloride Chemical compound Cl.NO.ON1C(C2=CC=CC=3C2=C(C1=O)C=C(C3)[N+](=O)[O-])=O UANDWKVBMWTMJE-UHFFFAOYSA-N 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
238000007654 immersion Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
238000005497 microtitration Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
235000013919 monopotassium glutamate Nutrition 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
230000035772 mutation Effects 0.000 description 1
PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 1
VYCXOFHKHFNYKH-UHFFFAOYSA-N n-(5,6-dichloro-1,2-dihydroacenaphthylen-3-yl)acetamide Chemical compound ClC1=CC=C2CCC3=C2C1=C(Cl)C=C3NC(=O)C VYCXOFHKHFNYKH-UHFFFAOYSA-N 0.000 description 1
DROSWABVSRWCEO-UHFFFAOYSA-N n-(8-acetamido-2-hydroxy-1,3-dioxobenzo[de]isoquinolin-5-yl)acetamide Chemical compound CC(=O)NC1=CC2=CC(NC(=O)C)=CC(C(=O)N(O)C3=O)=C2C3=C1 DROSWABVSRWCEO-UHFFFAOYSA-N 0.000 description 1
PHRWXBDLYFCTQE-UHFFFAOYSA-N n-[(2-hydroxy-5-methoxy-1,3-dioxobenzo[de]isoquinolin-6-yl)methyl]acetamide Chemical compound C1=CC2=C(CNC(C)=O)C(OC)=CC(C(=O)N(O)C3=O)=C2C3=C1 PHRWXBDLYFCTQE-UHFFFAOYSA-N 0.000 description 1
KHAMRMOSVBRUGE-UHFFFAOYSA-N n-[6-chloro-2-[(2-methylpropan-2-yl)oxy]-1,3-dioxobenzo[de]isoquinolin-5-yl]acetamide Chemical compound C1=CC2=C(Cl)C(NC(=O)C)=CC(C(=O)N(OC(C)(C)C)C3=O)=C2C3=C1 KHAMRMOSVBRUGE-UHFFFAOYSA-N 0.000 description 1
150000002790 naphthalenes Chemical class 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
ORAQFQGEIBFOCW-UHFFFAOYSA-N o-(1,3-dioxo-2-phenylmethoxybenzo[de]isoquinolin-5-yl) n,n-dimethylcarbamothioate Chemical compound O=C1C(C=23)=CC=CC3=CC(OC(=S)N(C)C)=CC=2C(=O)N1OCC1=CC=CC=C1 ORAQFQGEIBFOCW-UHFFFAOYSA-N 0.000 description 1
SSUCKKNRCOFUPT-UHFFFAOYSA-N o-[tert-butyl(dimethyl)silyl]hydroxylamine Chemical compound CC(C)(C)[Si](C)(C)ON SSUCKKNRCOFUPT-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
ZMLDXWLZKKZVSS-UHFFFAOYSA-N palladium tin Chemical compound [Pd].[Sn] ZMLDXWLZKKZVSS-UHFFFAOYSA-N 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
SDFVUQINJAUPSH-UHFFFAOYSA-M potassium;2-hydroxy-1,3-dioxobenzo[de]isoquinoline-6-sulfonate Chemical compound [K+].C1=CC(C(N(O)C2=O)=O)=C3C2=CC=CC3=C1S([O-])(=O)=O SDFVUQINJAUPSH-UHFFFAOYSA-M 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 1
229910000367 silver sulfate Inorganic materials 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000010959 steel Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003760 tallow Substances 0.000 description 1
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
239000012414 tert-butyl nitrite Substances 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
239000011345 viscous material Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
- 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
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/06—Peri-condensed systems
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Other In-Based Heterocyclic Compounds (AREA)

NO19992104A 1996-11-01 1999-04-30 Isokinoloner og fremgangsmåte for fremstilling derav NO314304B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2990996P	1996-11-01	1996-11-01
PCT/US1997/019872 WO1998019648A2 (fr)	1996-11-01	1997-10-31	Isoquinolones

Publications (3)

Publication Number	Publication Date
NO992104D0 NO992104D0 (no)	1999-04-30
NO992104L NO992104L (no)	1999-04-30
NO314304B1 true NO314304B1 (no)	2003-03-03

Family

ID=21851529

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19992104A NO314304B1 (no)	1996-11-01	1999-04-30	Isokinoloner og fremgangsmåte for fremstilling derav

Country Status (12)

Country	Link
US (2)	US6177423B1 (fr)
EP (1)	EP0939754A2 (fr)
JP (1)	JP2001505554A (fr)
KR (1)	KR20000052949A (fr)
AU (1)	AU748749B2 (fr)
BR (1)	BR9712715A (fr)
CA (1)	CA2263301A1 (fr)
IL (1)	IL128516A0 (fr)
NO (1)	NO314304B1 (fr)
NZ (1)	NZ334896A (fr)
PL (1)	PL333238A1 (fr)
WO (1)	WO1998019648A2 (fr)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7410746B2 (en) *	2002-03-29	2008-08-12	Dai Nippon Printing Co., Ltd.	Photoradical polymerization initiator, radical generator, photosensitive compound and photosensitive resin composition containing these materials and product or its accessory portions using the composition
WO2004004716A1 (fr) *	2002-07-08	2004-01-15	Chemgenex Pharmaceuticals Limited	Synthese de naphtalimides, y compris d'amonafides, et preparations pharmaceutiques les contenant
US7346199B2 (en) *	2002-11-30	2008-03-18	Intuitive Software, Inc.	Anatomic triangulation
AU2005209845A1 (en) *	2004-01-30	2005-08-18	Chemgenex Pharmaceuticals, Inc.	Naphthalimide dosing by N-acetyl transferase genotyping
WO2005117893A2 (fr) *	2004-06-04	2005-12-15	Chemgenex Pharmaceuticals, Inc.	Procedes de traitement de maladies proliferatives cellulaires au moyen de naphtalimide et d'inhibiteurs de parp-1
US20070213354A1 (en) *	2006-03-08	2007-09-13	Amplimed Corporation	Compositions and Methods for the Treatment of Multiple Sclerosis
AR061185A1 (es) *	2006-05-26	2008-08-13	Chugai Pharmaceutical Co Ltd	Compuestos heterociclicos como inhibidores de hsp90. composiciones farmaceuticas.
MX2009008756A (es)	2007-03-01	2009-08-27	Chugai Pharmaceutical Co Ltd	Compuesto macrociclico.
WO2011087011A1 (fr) *	2010-01-13	2011-07-21	株式会社Adeka	Nouveau composé dérivé d'acide sulfonique et nouveau composé dérivé d'acide naphtalique
CN103012185A (zh) *	2012-12-24	2013-04-03	辽宁本源制药有限公司	一种治疗抑郁症的药物阿戈美拉汀的制备方法
CN105492428A (zh) *	2013-05-01	2016-04-13	中央研究院	治疗β-地中海贫血和镰状细胞病的方法和组合物
CN106083850B (zh) *	2016-07-13	2018-01-02	河南大学	一类嘧啶并萘酰亚胺衍生物及其制备方法和应用
CN109384720B (zh) *	2018-11-01	2022-06-28	上海博栋化学科技有限公司	合成6-(2-甲氧基乙氧基)-n-羟基萘酰亚胺三氟甲磺酸的方法
CN109932349B (zh) *	2019-04-04	2021-04-20	济南大学	一种检测次氯酸的有机硅小分子荧光探针
CN110078666B (zh) *	2019-06-15	2023-01-24	山东省医学科学院药物研究所(山东省抗衰老研究中心山东省新技术制药研究所)	一种基于萘酰亚胺的镍离子荧光探针、制备方法及其应用
CN110194741B (zh) *	2019-07-08	2022-09-09	桂林医学院	4-苯甲酰哌嗪-3-硝基-1,8-萘酰亚胺衍生物及其制备方法和应用
CN110317171B (zh) *	2019-07-08	2022-06-17	桂林医学院	4-二硫代甲酸哌嗪-1,8-萘酰亚胺衍生物及其制备方法和应用
CN110272388B (zh) *	2019-07-08	2022-06-17	桂林医学院	4-二硫代甲酸哌嗪-3-硝基-1,8-萘酰亚胺衍生物及其合成方法和应用
CN110283123B (zh) *	2019-07-08	2022-06-17	桂林医学院	4-对甲苯磺酰基哌嗪-3-硝基-1,8-萘酰亚胺衍生物及其合成方法和应用
CN110283163B (zh) *	2019-07-08	2023-03-14	桂林医学院	4-叔丁氧羰基哌嗪-3-硝基-1,8-萘酰亚胺衍生物及其合成方法和应用
CN110194740B (zh) *	2019-07-08	2022-06-17	桂林医学院	4-叔丁氧羰基哌嗪-1,8-萘酰亚胺衍生物及其合成方法和应用

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5115057B1 (fr) *	1970-05-27	1976-05-14
JPS4914326B1 (fr) *	1970-07-31	1974-04-06
DE2114634A1 (de)	1971-03-26	1972-10-05	Badische Anilin- & Soda-Fabrik Ag, 6700 Ludwigshafen	Dispersionsfarbstoffe der Thioxanthenreihe
US3880859A (en)	1971-06-03	1975-04-29	Basf Ag	N-substituted-4-alkoxynaphthalimides
DE2147706A1 (de) *	1971-09-24	1973-03-29	Basf Ag	Verbindungen der naphthalimidreihe
BE788719A (fr)	1971-09-13	1973-01-02	Cabot Corp	Alliage a base de nickel resistant a l'oxydation aux temperatures elevees et thermiquement stables
US3941791A (en)	1972-06-28	1976-03-02	Basf Aktiengesellschaft	Compounds of the naphthalimide series
DE2231609C3 (de) *	1972-06-28	1980-09-04	Basf Ag, 6700 Ludwigshafen	Verbindungen der Naphthalimidreihe
DE2246111C3 (de) *	1972-09-20	1980-07-31	Hoechst Ag, 6000 Frankfurt	Verfahren zur Herstellung von Naphthalimid-43-dicarbonsäuren
US4007192A (en)	1972-09-20	1977-02-08	Hoechst Aktiengesellschaft	Naphthalimide-4,5-dicarboxylic acids
JPS5122935B2 (fr) *	1973-07-30	1976-07-13
DE2415027A1 (de) *	1974-03-28	1975-10-16	Basf Ag	Farbstoffe der naphthalimidreihe
DE2417789A1 (de)	1974-04-11	1975-10-30	Basf Ag	Naphtholactamderivate
JPS5116673A (en) *	1974-07-30	1976-02-10	Mitsubishi Chem Ind	Nitorochikan 4*55 jikuroronafutarusanimidono seizohoho
JPS51109020A (en) *	1975-03-22	1976-09-27	Nippon Kayaku Kk	1*88 nafutaarusanimidojudotaino shinkinaseiho
JPS5917111B2 (ja) *	1976-01-28	1984-04-19	三菱化学株式会社	ニトロ置換４，５−ジクロロナフタル酸イミド類
JPS6012352B2 (ja) *	1976-02-19	1985-04-01	日本化薬株式会社	染料中間体の製造法
JPS609503B2 (ja) *	1976-04-27	1985-03-11	日本化薬株式会社	テトラクロルナフタル酸イミド誘導体とその製造方法
JP2572458B2 (ja) *	1989-10-20	1997-01-16	富士写真フイルム株式会社	電子写真感光体
CA2030129A1 (fr)	1989-11-29	1991-05-30	Thomas Saupe	1,8-napthalenedicarboximides utilises comme antidotes
JPH053671A (ja) *	1991-01-24	1993-01-08	Tdk Corp	Ｄｃ−ｄｃコンバータ
JPH05774A (ja) *	1991-04-23	1993-01-08	Nisca Corp	原稿給送装置
AUPM910994A0 (en) *	1994-10-28	1994-11-24	Commonwealth Scientific And Industrial Research Organisation	Bisallyloxyimides
DE19612193A1 (de) *	1996-03-27	1997-10-02	Consortium Elektrochem Ind	Mehrkomponentensystem zum Verändern, Abbau oder Bleichen von Lignin, ligninhaltigen Materialien oder ähnlichen Stoffen sowie Verfahren zu seiner Anwendung

1997
- 1997-10-31 US US09/254,645 patent/US6177423B1/en not_active Expired - Fee Related
- 1997-10-31 WO PCT/US1997/019872 patent/WO1998019648A2/fr not_active Ceased
- 1997-10-31 JP JP52161898A patent/JP2001505554A/ja not_active Abandoned
- 1997-10-31 KR KR1019990703822A patent/KR20000052949A/ko not_active Ceased
- 1997-10-31 IL IL12851697A patent/IL128516A0/xx unknown
- 1997-10-31 PL PL97333238A patent/PL333238A1/xx unknown
- 1997-10-31 AU AU51604/98A patent/AU748749B2/en not_active Ceased
- 1997-10-31 BR BR9712715-9A patent/BR9712715A/pt not_active Application Discontinuation
- 1997-10-31 CA CA002263301A patent/CA2263301A1/fr not_active Abandoned
- 1997-10-31 EP EP97946438A patent/EP0939754A2/fr not_active Withdrawn
- 1997-10-31 NZ NZ334896A patent/NZ334896A/xx unknown
1999
- 1999-04-30 NO NO19992104A patent/NO314304B1/no not_active IP Right Cessation
2000
- 2000-08-11 US US09/637,949 patent/US6362181B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IL128516A0 (en)	2000-01-31
WO1998019648A3 (fr)	1999-03-04
AU748749B2 (en)	2002-06-13
CA2263301A1 (fr)	1998-05-14
WO1998019648A2 (fr)	1998-05-14
US6362181B1 (en)	2002-03-26
NO992104D0 (no)	1999-04-30
NO992104L (no)	1999-04-30
NZ334896A (en)	2001-01-26
BR9712715A (pt)	2000-05-16
AU5160498A (en)	1998-05-29
JP2001505554A (ja)	2001-04-24
KR20000052949A (ko)	2000-08-25
PL333238A1 (en)	1999-11-22
EP0939754A2 (fr)	1999-09-08
US6177423B1 (en)	2001-01-23

Legal Events

Date	Code	Title	Description
2004-10-18	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO314304B1 (no)	2003-03-03	Isokinoloner og fremgangsmåte for fremstilling derav
Ding et al.	1999	Pyrroloquinoline and Pyridoacridine Alkaloids from Marine
US20040138230A1 (en)	2004-07-15	Heterocyclic substituted piperazines for the treatment of schizophrenia
US20050171101A1 (en)	2005-08-04	Phenanthridinones as parp inhibitors
CA2643488C (fr)	2014-08-05	Iindolopyridines servant de modulateurs d'eg5 kinesine
IE913307A1 (en)	1992-04-08	Process for the preparation of imidazo[4,5-c]quinolin-4-amines
OA12316A (en)	2006-05-15	3-Aminoquinazolin-2,4-dione antibacterial agents.
WO2002074754A1 (fr)	2002-09-26	Nouveaux derives spirotricycliques et leur utilisation en tant qu'inhibiteurs de la phosphodiesterase-7
JP2002533465A (ja)	2002-10-08	Ｘａ因子阻害剤としての窒素を含む複素二環類
AU721102B2 (en)	2000-06-22	1H-pyrido{3,4-b}indole-4-carboxamide derivatives, their preparation and their application in therapeutics
NZ272516A (en)	1996-10-28	Pyrrolopyridine and oxazolopyridine derivatives and medicaments thereof
US5910498A (en)	1999-06-08	Pyridonecarboxylic acid derivatives or salts thereof and antibacterial agents comprising the same as active ingredient
EP3383858A1 (fr)	2018-10-10	Inhibiteurs de métallo-bêta-lactamases
JPH03193780A (ja)	1991-08-23	キノロン化合物およびその製法
Rivalle et al.	1983	Antitumor amino-substituted pyrido [3', 4': 4, 5] pyrrolo [2, 3-g] isoquinolines and pyrido [4, 3-b] carbazole derivatives: synthesis and evaluation of compounds resulting from new side chain and heterocycle modifications
NO129954B (fr)	1974-06-17
NO863790L (no)	1987-03-25	Kinolinderivater.
RU2284325C2 (ru)	2006-09-27	Производные фенил-3-аминометил-хинолона-2 в качестве ингибиторов no-синтетазы, способ их получения, биологически активные соединения и фармацевтическая композиция на их основе
Khoje et al.	2011	Synthesis and antimycobacterial activities of non-purine analogs of 6-aryl-9-benzylpurines: Imidazopyridines, pyrrolopyridines, benzimidazoles, and indoles
WO2006054912A1 (fr)	2006-05-26	Derives d'aryl(hetaryl)-3-aminomethylchinolone-2 utilises en tant qu'inhibiteurs de no-synthetase et de cyclo-oxygenase-2, procedes de leur fabrication et compositions pharmaceutiques sur leur base
JPH03193779A (ja)	1991-08-23	ジアザビシクロアミン化合物およびその製法
El-Gendy et al.	2000	Synthesis and antimicrobial activity of some new 2-indolinone derived oximes and spiro-isoxazolines
Hutchinson et al.	2007	Synthetic strategies to a telomere-targeted pentacyclic heteroaromatic salt
Hutchinson et al.	2004	Synthesis and properties of bioactive 2-and 3-amino-8-methyl-8H-quino [4, 3, 2-kl] acridine and 8, 13-dimethyl-8 H-quino [4, 3, 2-kl] acridinium salts
US5356903A (en)	1994-10-18	1-cyclopropyl-4-pyridyl-quinolines