JP5368317B2 - 新規なインドール誘導体それらの製造方法および特に抗菌剤としてのそれらの使用 - Google Patents
新規なインドール誘導体それらの製造方法および特に抗菌剤としてのそれらの使用 Download PDFInfo
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- JP5368317B2 JP5368317B2 JP2009547728A JP2009547728A JP5368317B2 JP 5368317 B2 JP5368317 B2 JP 5368317B2 JP 2009547728 A JP2009547728 A JP 2009547728A JP 2009547728 A JP2009547728 A JP 2009547728A JP 5368317 B2 JP5368317 B2 JP 5368317B2
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- 238000004519 manufacturing process Methods 0.000 title claims description 22
- 150000002475 indoles Chemical class 0.000 title abstract description 32
- 229940054051 antipsychotic indole derivative Drugs 0.000 title abstract description 9
- 239000003242 anti bacterial agent Substances 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 370
- 238000000034 method Methods 0.000 claims abstract description 98
- 125000003118 aryl group Chemical group 0.000 claims abstract description 62
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 60
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 56
- -1 t-butoxycarbonyl Chemical group 0.000 claims abstract description 46
- 239000000203 mixture Substances 0.000 claims abstract description 45
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 44
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 13
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims abstract description 9
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 9
- 229960003405 ciprofloxacin Drugs 0.000 claims abstract description 7
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 230000003115 biocidal effect Effects 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 179
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 123
- 125000004432 carbon atom Chemical group C* 0.000 claims description 98
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 81
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 58
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 52
- 239000008194 pharmaceutical composition Substances 0.000 claims description 41
- 239000000460 chlorine Substances 0.000 claims description 35
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
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- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 125000003277 amino group Chemical group 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 17
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 16
- 235000019253 formic acid Nutrition 0.000 claims description 13
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 10
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 10
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 8
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
- 239000004599 antimicrobial Substances 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
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- 229960003702 moxifloxacin Drugs 0.000 claims description 5
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 claims description 5
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 229960001180 norfloxacin Drugs 0.000 claims description 4
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims description 4
- 229960001699 ofloxacin Drugs 0.000 claims description 4
- FHFYDNQZQSQIAI-UHFFFAOYSA-N pefloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 FHFYDNQZQSQIAI-UHFFFAOYSA-N 0.000 claims description 4
- 229960004236 pefloxacin Drugs 0.000 claims description 4
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 150000003891 oxalate salts Chemical class 0.000 claims description 2
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 claims description 2
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims 2
- 230000007774 longterm Effects 0.000 claims 1
- 235000021419 vinegar Nutrition 0.000 claims 1
- 239000000052 vinegar Substances 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 abstract description 15
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 9
- 229910052786 argon Inorganic materials 0.000 abstract description 7
- 241000191967 Staphylococcus aureus Species 0.000 abstract description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 abstract description 3
- 125000004665 trialkylsilyl group Chemical group 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 abstract 3
- 125000005002 aryl methyl group Chemical group 0.000 abstract 2
- MGTCYBNMLWDAMV-UHFFFAOYSA-N 1-(5-methoxy-1h-indol-3-yl)ethane-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.COC1=CC=C2NC=C(C(N)CN)C2=C1 MGTCYBNMLWDAMV-UHFFFAOYSA-N 0.000 abstract 1
- OQCVUUKCUJKNDP-UHFFFAOYSA-N 1-(6-bromo-1h-indol-3-yl)ethane-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.BrC1=CC=C2C(C(N)CN)=CNC2=C1 OQCVUUKCUJKNDP-UHFFFAOYSA-N 0.000 abstract 1
- VTMMGUVHELVTKO-UHFFFAOYSA-N 1-(6-methoxy-1h-indol-3-yl)ethane-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.COC1=CC=C2C(C(N)CN)=CNC2=C1 VTMMGUVHELVTKO-UHFFFAOYSA-N 0.000 abstract 1
- OTCCIMWXFLJLIA-BYPYZUCNSA-N N-acetyl-L-aspartic acid Chemical compound CC(=O)N[C@H](C(O)=O)CC(O)=O OTCCIMWXFLJLIA-BYPYZUCNSA-N 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract 1
- 230000010534 mechanism of action Effects 0.000 abstract 1
- HYVUKNAJCMXHLR-UHFFFAOYSA-N n-[(2,4-dimethoxyphenyl)methyl]-n-[1-(1h-indol-3-yl)-3-methylbutyl]hydroxylamine Chemical compound COC1=CC(OC)=CC=C1CN(O)C(CC(C)C)C1=CNC2=CC=CC=C12 HYVUKNAJCMXHLR-UHFFFAOYSA-N 0.000 abstract 1
- DREIZUYRWZZCQR-UHFFFAOYSA-N n-[1-(5-bromo-1h-indol-3-yl)ethyl]-1-phenylmethanimine oxide Chemical compound C=1NC2=CC=C(Br)C=C2C=1C(C)[N+]([O-])=CC1=CC=CC=C1 DREIZUYRWZZCQR-UHFFFAOYSA-N 0.000 abstract 1
- JZDCUKFBSYLMMW-UHFFFAOYSA-N n-[1-(5-bromo-1h-indol-3-yl)ethyl]-n-[(4-methoxyphenyl)methyl]hydroxylamine Chemical compound C1=CC(OC)=CC=C1CN(O)C(C)C1=CNC2=CC=C(Br)C=C12 JZDCUKFBSYLMMW-UHFFFAOYSA-N 0.000 abstract 1
- PGOHTJCTDDUUPZ-UHFFFAOYSA-N n-[1-(5-bromo-1h-indol-3-yl)propyl]-1-phenylmethanimine oxide Chemical compound C=1NC2=CC=C(Br)C=C2C=1C(CC)[N+]([O-])=CC1=CC=CC=C1 PGOHTJCTDDUUPZ-UHFFFAOYSA-N 0.000 abstract 1
- CTUSTYRZIIPQNU-UHFFFAOYSA-N n-[2-amino-1-(5-bromo-1h-indol-3-yl)ethyl]hydroxylamine;dihydrochloride Chemical compound Cl.Cl.C1=C(Br)C=C2C(C(NO)CN)=CNC2=C1 CTUSTYRZIIPQNU-UHFFFAOYSA-N 0.000 abstract 1
- BXUUXZARCKWJNI-UHFFFAOYSA-N n-[2-amino-1-(6-bromo-1h-indol-3-yl)ethyl]hydroxylamine;dihydrochloride Chemical compound Cl.Cl.BrC1=CC=C2C(C(NO)CN)=CNC2=C1 BXUUXZARCKWJNI-UHFFFAOYSA-N 0.000 abstract 1
- GTJGJVIGLIPMQC-UHFFFAOYSA-N n-benzyl-n-[1-(5-bromo-1h-indol-3-yl)ethyl]hydroxylamine Chemical compound C=1NC2=CC=C(Br)C=C2C=1C(C)N(O)CC1=CC=CC=C1 GTJGJVIGLIPMQC-UHFFFAOYSA-N 0.000 abstract 1
- RCKFKEZJMDLKSA-UHFFFAOYSA-N n-benzyl-n-[1-(5-chloro-1h-indol-3-yl)ethyl]hydroxylamine Chemical compound C=1NC2=CC=C(Cl)C=C2C=1C(C)N(O)CC1=CC=CC=C1 RCKFKEZJMDLKSA-UHFFFAOYSA-N 0.000 abstract 1
- DPEMYJVFCNFSHS-UHFFFAOYSA-N n-benzyl-n-[1-(6-bromo-1h-indol-3-yl)ethyl]hydroxylamine Chemical compound C=1NC2=CC(Br)=CC=C2C=1C(C)N(O)CC1=CC=CC=C1 DPEMYJVFCNFSHS-UHFFFAOYSA-N 0.000 abstract 1
- RDKPVIJLBFLRBX-UHFFFAOYSA-N n-benzyl-n-[1h-indol-3-yl-(4-nitrophenyl)methyl]hydroxylamine Chemical compound C=1NC2=CC=CC=C2C=1C(C=1C=CC(=CC=1)[N+]([O-])=O)N(O)CC1=CC=CC=C1 RDKPVIJLBFLRBX-UHFFFAOYSA-N 0.000 abstract 1
- AJMKNEKNXAIYFQ-UHFFFAOYSA-N tert-butyl n-[1-(1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamate Chemical compound C1=CC=C2C(C(NC(=O)OC(C)(C)C)CNC(=O)OC(C)(C)C)=CNC2=C1 AJMKNEKNXAIYFQ-UHFFFAOYSA-N 0.000 abstract 1
- PHRYUWPTTNPDFE-UHFFFAOYSA-N tert-butyl n-[1-(5-bromo-1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamate Chemical compound C1=C(Br)C=C2C(C(NC(=O)OC(C)(C)C)CNC(=O)OC(C)(C)C)=CNC2=C1 PHRYUWPTTNPDFE-UHFFFAOYSA-N 0.000 abstract 1
- BRBUXKPSKYCZLZ-UHFFFAOYSA-N tert-butyl n-[1-(6-bromo-1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-n-hydroxycarbamate Chemical compound BrC1=CC=C2C(C(N(O)C(=O)OC(C)(C)C)CNC(=O)OC(C)(C)C)=CNC2=C1 BRBUXKPSKYCZLZ-UHFFFAOYSA-N 0.000 abstract 1
- UGBBJBSWJUGMOW-UHFFFAOYSA-N tert-butyl n-[1-(6-bromo-1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamate Chemical compound BrC1=CC=C2C(C(NC(=O)OC(C)(C)C)CNC(=O)OC(C)(C)C)=CNC2=C1 UGBBJBSWJUGMOW-UHFFFAOYSA-N 0.000 abstract 1
- DUPLPTVSQPRSSI-UHFFFAOYSA-N tert-butyl n-[2-(5-bromo-1h-indol-3-yl)-2-(hydroxyamino)ethyl]carbamate Chemical compound C1=C(Br)C=C2C(C(NO)CNC(=O)OC(C)(C)C)=CNC2=C1 DUPLPTVSQPRSSI-UHFFFAOYSA-N 0.000 abstract 1
- KLHBYDWIHVKENU-UHFFFAOYSA-N tert-butyl n-[2-(5-bromo-1h-indol-3-yl)-2-[hydroxy-[(4-methoxyphenyl)methyl]amino]ethyl]carbamate Chemical compound C1=CC(OC)=CC=C1CN(O)C(CNC(=O)OC(C)(C)C)C1=CNC2=CC=C(Br)C=C12 KLHBYDWIHVKENU-UHFFFAOYSA-N 0.000 abstract 1
- JIJDQZCQZVESSF-UHFFFAOYSA-N tert-butyl n-[2-(6-bromo-1h-indol-3-yl)-2-(hydroxyamino)ethyl]carbamate Chemical compound BrC1=CC=C2C(C(NO)CNC(=O)OC(C)(C)C)=CNC2=C1 JIJDQZCQZVESSF-UHFFFAOYSA-N 0.000 abstract 1
- NUFGHVNOAYWBFV-UHFFFAOYSA-N tert-butyl n-[2-amino-2-(6-bromo-1h-indol-3-yl)ethyl]carbamate Chemical compound BrC1=CC=C2C(C(N)CNC(=O)OC(C)(C)C)=CNC2=C1 NUFGHVNOAYWBFV-UHFFFAOYSA-N 0.000 abstract 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 383
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 194
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 192
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 154
- 238000003786 synthesis reaction Methods 0.000 description 73
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- 239000000243 solution Substances 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
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- 238000006243 chemical reaction Methods 0.000 description 26
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000007787 solid Substances 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
- 125000001041 indolyl group Chemical group 0.000 description 18
- 229910052794 bromium Inorganic materials 0.000 description 17
- 229910052731 fluorine Inorganic materials 0.000 description 16
- 239000002609 medium Substances 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 229910052740 iodine Inorganic materials 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
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- 239000003480 eluent Substances 0.000 description 13
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- OWYJZQFASFWUHP-UHFFFAOYSA-N hydroxylamine;1h-indole Chemical compound ON.C1=CC=C2NC=CC2=C1 OWYJZQFASFWUHP-UHFFFAOYSA-N 0.000 description 10
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- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 9
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- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 8
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- 239000000543 intermediate Substances 0.000 description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 230000000704 physical effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 239000012429 reaction media Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
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- 239000006994 mh medium Substances 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 101150021123 msrA gene Proteins 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- RZSCFTDHFNHMOR-UHFFFAOYSA-N n-(2,4-difluorophenyl)-2-[3-(trifluoromethyl)phenoxy]pyridine-3-carboxamide;1,1-dimethyl-3-(4-propan-2-ylphenyl)urea Chemical compound CC(C)C1=CC=C(NC(=O)N(C)C)C=C1.FC1=CC(F)=CC=C1NC(=O)C1=CC=CN=C1OC1=CC=CC(C(F)(F)F)=C1 RZSCFTDHFNHMOR-UHFFFAOYSA-N 0.000 description 1
- SDLZRPHXJNFLIO-UHFFFAOYSA-N n-(benzotriazol-1-ylmethyl)-n-benzyl-1-phenylmethanamine Chemical compound C=1C=CC=CC=1CN(CN1C2=CC=CC=C2N=N1)CC1=CC=CC=C1 SDLZRPHXJNFLIO-UHFFFAOYSA-N 0.000 description 1
- LKDZJQQFFSQJIP-UHFFFAOYSA-N n-benzyl-2-phenylmethoxyethanimine oxide Chemical compound C=1C=CC=CC=1COCC=[N+]([O-])CC1=CC=CC=C1 LKDZJQQFFSQJIP-UHFFFAOYSA-N 0.000 description 1
- LVCDXCQFSONNDO-UHFFFAOYSA-N n-benzylhydroxylamine Chemical compound ONCC1=CC=CC=C1 LVCDXCQFSONNDO-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- ZYHMJXZULPZUED-UHFFFAOYSA-N propargite Chemical compound C1=CC(C(C)(C)C)=CC=C1OC1C(OS(=O)OCC#C)CCCC1 ZYHMJXZULPZUED-UHFFFAOYSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039447 salmonellosis Diseases 0.000 description 1
- UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- MYGOYMSRXQRMCG-UHFFFAOYSA-N sodium;5-bromoindol-1-ide Chemical compound [Na+].BrC1=CC=C2[N-]C=CC2=C1 MYGOYMSRXQRMCG-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KFBVOHFZYVKSPY-UHFFFAOYSA-N tert-butyl 2-aminoindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(N)=CC2=C1 KFBVOHFZYVKSPY-UHFFFAOYSA-N 0.000 description 1
- LPSLGTZFBDZNEK-UHFFFAOYSA-N tert-butyl 5-methoxyindole-1-carboxylate Chemical compound COC1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 LPSLGTZFBDZNEK-UHFFFAOYSA-N 0.000 description 1
- MEOVARDOZULBTL-UHFFFAOYSA-N tert-butyl-indol-1-yl-dimethylsilane Chemical compound C1=CC=C2N([Si](C)(C)C(C)(C)C)C=CC2=C1 MEOVARDOZULBTL-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0700717 | 2007-02-01 | ||
| FR0700717A FR2912133B1 (fr) | 2007-02-01 | 2007-02-01 | Nouveaux derives indoliques,leurs procedes de preparation et leurs utilisations notamment en tant qu'antibacteriens |
| PCT/FR2008/000118 WO2008110690A2 (fr) | 2007-02-01 | 2008-01-31 | Nouveaux derives indoliques, leurs procedes de preparation et leurs utilisations notamment en tant qu'antibacteriens |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010517983A JP2010517983A (ja) | 2010-05-27 |
| JP2010517983A5 JP2010517983A5 (https=) | 2010-12-02 |
| JP5368317B2 true JP5368317B2 (ja) | 2013-12-18 |
Family
ID=38476052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009547728A Expired - Fee Related JP5368317B2 (ja) | 2007-02-01 | 2008-01-31 | 新規なインドール誘導体それらの製造方法および特に抗菌剤としてのそれらの使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8343964B2 (https=) |
| EP (1) | EP2121601B8 (https=) |
| JP (1) | JP5368317B2 (https=) |
| CN (1) | CN101652346B (https=) |
| AU (1) | AU2008224776B2 (https=) |
| CA (1) | CA2677146C (https=) |
| FR (1) | FR2912133B1 (https=) |
| RU (1) | RU2464261C2 (https=) |
| WO (1) | WO2008110690A2 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011060976A1 (en) | 2009-11-20 | 2011-05-26 | Universite De Liege | Tryptamine-derived compounds as antibacterial agents |
| FR2969150B1 (fr) * | 2010-12-20 | 2013-07-26 | Centre Nat Rech Scient | Nouvelles molecules indoliques demontrant des activites antibacteriennes dans une variete de bacteries a gram-negatif et positif dont des bacteries multidrogues-resistantes |
| ES2464598T3 (es) | 2011-07-22 | 2014-06-03 | Université Joseph Fourier | Nuevos derivados bis-indólicos, procedimiento para su preparación, y sus utilizaciones como fármaco |
| EP2548865B1 (en) | 2011-07-22 | 2014-03-05 | Université Joseph Fourier | Novel bis-indolic derivatives, their uses in particular as antibacterials |
| EP2639220A1 (en) * | 2012-03-15 | 2013-09-18 | Omnia Molecular, S. L. | Indole derivatives and their use as antibiotics |
| CN103664733B (zh) * | 2013-12-10 | 2016-04-20 | 邯郸惠达化工有限公司 | 一种吲哚啉的制备方法 |
| CN105669519B (zh) * | 2016-01-04 | 2018-01-05 | 北方民族大学 | 吲哚类化合物、制备方法及其作为抗耐药菌药物的应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4492694A (en) * | 1983-04-12 | 1985-01-08 | Eli Lilly And Company | Indolylglycyl cephalosporin derivatives |
| US5328902A (en) * | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| CA2444597A1 (en) * | 2001-04-06 | 2002-10-06 | Affinium Pharmaceuticals, Inc. | Fab i inhibitors |
| DE602004016831D1 (de) * | 2003-03-17 | 2008-11-13 | Affinium Pharm Inc | Pharmazeutische zusammensetzungen inhibitoren von fab i und weitere antibiotika enthaltend |
| DE10320453A1 (de) * | 2003-05-08 | 2004-11-25 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Bioisostere von Actinonin |
-
2007
- 2007-02-01 FR FR0700717A patent/FR2912133B1/fr not_active Expired - Fee Related
-
2008
- 2008-01-31 AU AU2008224776A patent/AU2008224776B2/en not_active Ceased
- 2008-01-31 JP JP2009547728A patent/JP5368317B2/ja not_active Expired - Fee Related
- 2008-01-31 EP EP08761826.0A patent/EP2121601B8/fr not_active Not-in-force
- 2008-01-31 RU RU2009132657/04A patent/RU2464261C2/ru not_active IP Right Cessation
- 2008-01-31 US US12/525,503 patent/US8343964B2/en not_active Expired - Fee Related
- 2008-01-31 WO PCT/FR2008/000118 patent/WO2008110690A2/fr not_active Ceased
- 2008-01-31 CA CA2677146A patent/CA2677146C/fr not_active Expired - Fee Related
- 2008-01-31 CN CN2008800097669A patent/CN101652346B/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| FR2912133B1 (fr) | 2009-04-24 |
| EP2121601A2 (fr) | 2009-11-25 |
| RU2464261C2 (ru) | 2012-10-20 |
| RU2009132657A (ru) | 2011-03-10 |
| EP2121601B1 (fr) | 2016-06-15 |
| AU2008224776A1 (en) | 2008-09-18 |
| US20100144726A1 (en) | 2010-06-10 |
| FR2912133A1 (fr) | 2008-08-08 |
| EP2121601B8 (fr) | 2016-12-07 |
| CA2677146C (fr) | 2016-11-15 |
| CA2677146A1 (fr) | 2008-09-18 |
| WO2008110690A3 (fr) | 2009-03-19 |
| US8343964B2 (en) | 2013-01-01 |
| CN101652346A (zh) | 2010-02-17 |
| CN101652346B (zh) | 2013-10-30 |
| AU2008224776B2 (en) | 2012-09-06 |
| JP2010517983A (ja) | 2010-05-27 |
| WO2008110690A2 (fr) | 2008-09-18 |
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