JP2005508350A - キノリン誘導体、合成法およびこれらの誘導体を含有する薬剤 - Google Patents
キノリン誘導体、合成法およびこれらの誘導体を含有する薬剤 Download PDFInfo
- Publication number
- JP2005508350A JP2005508350A JP2003534397A JP2003534397A JP2005508350A JP 2005508350 A JP2005508350 A JP 2005508350A JP 2003534397 A JP2003534397 A JP 2003534397A JP 2003534397 A JP2003534397 A JP 2003534397A JP 2005508350 A JP2005508350 A JP 2005508350A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- defined above
- derivatives
- group
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940079593 drug Drugs 0.000 title description 6
- 239000003814 drug Substances 0.000 title description 6
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 5
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 2
- 238000010189 synthetic method Methods 0.000 title 1
- -1 -COOR Chemical group 0.000 claims abstract description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 150000003248 quinolines Chemical class 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- GKHAQRADKBTIKK-UHFFFAOYSA-N 2-carbamoyl-8-hydroxyquinoline-7-carboxylic acid Chemical class C1=CC(C(O)=O)=C(O)C2=NC(C(=O)N)=CC=C21 GKHAQRADKBTIKK-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 20
- 150000001408 amides Chemical class 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000007127 saponification reaction Methods 0.000 claims description 8
- IMTUBZOIPOXUTD-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) quinoline-2-carboxylate Chemical compound C=1C=C2C=CC=CC2=NC=1C(=O)ON1C(=O)CCC1=O IMTUBZOIPOXUTD-UHFFFAOYSA-N 0.000 claims description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- 125000006850 spacer group Chemical group 0.000 claims description 6
- GFYMLRYNGZEAFF-UHFFFAOYSA-N 2-[(3,4-dihydroxyphenyl)methylcarbamoyl]-8-hydroxyquinoline-7-carboxylic acid Chemical compound N=1C2=C(O)C(C(=O)O)=CC=C2C=CC=1C(=O)NCC1=CC=C(O)C(O)=C1 GFYMLRYNGZEAFF-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 230000020477 pH reduction Effects 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 230000002411 adverse Effects 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims 1
- 108010061833 Integrases Proteins 0.000 abstract description 11
- 102100034343 Integrase Human genes 0.000 abstract description 8
- 230000000798 anti-retroviral effect Effects 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 21
- 239000000203 mixture Substances 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 108020005202 Viral DNA Proteins 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000001177 retroviral effect Effects 0.000 description 9
- 238000004454 trace mineral analysis Methods 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 7
- 150000005690 diesters Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 230000001629 suppression Effects 0.000 description 7
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- RNQDBXNSZOJBET-UHFFFAOYSA-N 7-butoxycarbonyl-8-(2,2-dimethylpropanoyloxy)quinoline-2-carboxylic acid Chemical compound C1=CC(C(O)=O)=NC2=C(OC(=O)C(C)(C)C)C(C(=O)OCCCC)=CC=C21 RNQDBXNSZOJBET-UHFFFAOYSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 108010005774 beta-Galactosidase Proteins 0.000 description 5
- JTNSFKLTKATYTI-UHFFFAOYSA-N butyl 8-hydroxy-2-methylquinoline-7-carboxylate Chemical compound C1=CC(C)=NC2=C(O)C(C(=O)OCCCC)=CC=C21 JTNSFKLTKATYTI-UHFFFAOYSA-N 0.000 description 5
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- SHOHIXCIFBPUAP-UHFFFAOYSA-N 8-hydroxy-2-methylquinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=C(O)C2=NC(C)=CC=C21 SHOHIXCIFBPUAP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102000012330 Integrases Human genes 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 4
- NRHGWGQCOPJYCX-UHFFFAOYSA-N butyl 2-[(3,4-dihydroxyphenyl)methylcarbamoyl]-8-(2,2-dimethylpropanoyloxy)quinoline-7-carboxylate Chemical compound N=1C2=C(OC(=O)C(C)(C)C)C(C(=O)OCCCC)=CC=C2C=CC=1C(=O)NCC1=CC=C(O)C(O)=C1 NRHGWGQCOPJYCX-UHFFFAOYSA-N 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UYYRDZGZGNYVBA-VPXCCNNISA-N (2s,3r,4s,5r,6r)-2-[2-chloro-4-[3-(3-chloro-4-hydroxyphenyl)-1,1-dioxo-2,1$l^{6}-benzoxathiol-3-yl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(C2(C3=CC=CC=C3S(=O)(=O)O2)C=2C=C(Cl)C(O)=CC=2)C=C1Cl UYYRDZGZGNYVBA-VPXCCNNISA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 239000012979 RPMI medium Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- UVWATGDJAMJFHP-UHFFFAOYSA-M sodium;2-[(3,4-dihydroxyphenyl)methylcarbamoyl]-8-hydroxyquinoline-7-carboxylate Chemical compound [Na+].C1=C(O)C(O)=CC=C1CNC(=O)C1=CC=C(C=CC(C([O-])=O)=C2O)C2=N1 UVWATGDJAMJFHP-UHFFFAOYSA-M 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- XCUIQBHAIMNBMZ-UHFFFAOYSA-N 2-[(2,4-dihydroxyphenyl)methylcarbamoyl]-8-hydroxyquinoline-7-carboxylic acid Chemical compound N=1C2=C(O)C(C(=O)O)=CC=C2C=CC=1C(=O)NCC1=CC=C(O)C=C1O XCUIQBHAIMNBMZ-UHFFFAOYSA-N 0.000 description 2
- CGYMZQQWBJUGLK-UHFFFAOYSA-N 4-(aminomethyl)benzene-1,2-diol;4-methylbenzenesulfonic acid Chemical compound NCC1=CC=C(O)C(O)=C1.CC1=CC=C(S(O)(=O)=O)C=C1 CGYMZQQWBJUGLK-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108700020129 Human immunodeficiency virus 1 p31 integrase Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 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
- 229910052748 manganese Inorganic materials 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 2
- 229960002218 sodium chlorite Drugs 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- ZKDWFZXTRVTFRR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) quinoline-6-carboxylate Chemical compound O=C(ON1C(=O)CCC1=O)C1=CC=C2N=CC=CC2=C1 ZKDWFZXTRVTFRR-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
- LKOJGUIQTPXLPY-UHFFFAOYSA-N 8-(2,2-dimethylpropanoyloxy)-2-formylquinoline-7-carboxylic acid Chemical compound C1=C(C=O)N=C2C(OC(=O)C(C)(C)C)=C(C(O)=O)C=CC2=C1 LKOJGUIQTPXLPY-UHFFFAOYSA-N 0.000 description 1
- FTOLVLYBMNNTMN-UHFFFAOYSA-N 8-(2,2-dimethylpropanoyloxy)-2-methylquinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=C(OC(=O)C(C)(C)C)C2=NC(C)=CC=C21 FTOLVLYBMNNTMN-UHFFFAOYSA-N 0.000 description 1
- IITSQEXMDOMDMJ-UHFFFAOYSA-N 8-hydroxy-2-[(2,3,4-trihydroxyphenyl)methylcarbamoyl]quinoline-7-carboxylic acid Chemical compound N=1C2=C(O)C(C(=O)O)=CC=C2C=CC=1C(=O)NCC1=CC=C(O)C(O)=C1O IITSQEXMDOMDMJ-UHFFFAOYSA-N 0.000 description 1
- 108091023043 Alu Element Proteins 0.000 description 1
- KLCMWUIXAJXKTQ-UHFFFAOYSA-N Cc1ccc(ccc(C)n2)c2c1O Chemical compound Cc1ccc(ccc(C)n2)c2c1O KLCMWUIXAJXKTQ-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 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
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 1
- XOLJZNUTRCKLIG-UHFFFAOYSA-N butyl 8-(2,2-dimethylpropanoyloxy)-2-formylquinoline-7-carboxylate Chemical compound C1=CC(C=O)=NC2=C(OC(=O)C(C)(C)C)C(C(=O)OCCCC)=CC=C21 XOLJZNUTRCKLIG-UHFFFAOYSA-N 0.000 description 1
- MLJVNRYWWREFET-UHFFFAOYSA-N butyl 8-(2,2-dimethylpropanoyloxy)-2-methylquinoline-7-carboxylate Chemical compound C1=CC(C)=NC2=C(OC(=O)C(C)(C)C)C(C(=O)OCCCC)=CC=C21 MLJVNRYWWREFET-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002616 endonucleolytic effect Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000035892 strand transfer Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0113209A FR2830863B1 (fr) | 2001-10-12 | 2001-10-12 | Derives de quinoleine, procede de synthese, et medicaments renfermant ces derives |
| PCT/FR2002/003512 WO2003031413A1 (fr) | 2001-10-12 | 2002-10-14 | Derives de quinoleine, procede de synthese, et medicaments renfermant ces derives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005508350A true JP2005508350A (ja) | 2005-03-31 |
| JP2005508350A5 JP2005508350A5 (enExample) | 2006-01-05 |
Family
ID=8868255
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003534397A Pending JP2005508350A (ja) | 2001-10-12 | 2002-10-14 | キノリン誘導体、合成法およびこれらの誘導体を含有する薬剤 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US7064133B2 (enExample) |
| EP (1) | EP1461319B1 (enExample) |
| JP (1) | JP2005508350A (enExample) |
| AT (1) | ATE430134T1 (enExample) |
| DE (1) | DE60232186D1 (enExample) |
| DK (1) | DK1461319T3 (enExample) |
| ES (1) | ES2326115T3 (enExample) |
| FR (1) | FR2830863B1 (enExample) |
| IL (2) | IL161320A0 (enExample) |
| WO (1) | WO2003031413A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2830863B1 (fr) * | 2001-10-12 | 2004-01-30 | Bioalliance Pharma | Derives de quinoleine, procede de synthese, et medicaments renfermant ces derives |
| FR2839646B1 (fr) | 2002-05-17 | 2008-04-11 | Bioalliance Pharma | Utilisation de derives de quinoleine a effet anti-integrase et ses applications |
| US7132432B2 (en) * | 2003-06-05 | 2006-11-07 | Bristol-Myers Squibb Company | Hydantoin derivatives as inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) |
| TW200510425A (en) | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
| WO2005028478A1 (en) | 2003-09-19 | 2005-03-31 | Gilead Sciences, Inc. | Aza-quinolinol phosphonate integrase inhibitor compounds |
| WO2006129134A1 (en) * | 2005-06-01 | 2006-12-07 | Bioalliance Pharma | Synergic combinations comprising a styrylquinoline compound and other hiv infection therapeutic agents |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2761687B1 (fr) * | 1997-04-08 | 2000-09-15 | Centre Nat Rech Scient | Derives de quinoleines, possedant notamment des proprietes antivirales, leurs preparations et leurs applications biologiques |
| FR2830863B1 (fr) * | 2001-10-12 | 2004-01-30 | Bioalliance Pharma | Derives de quinoleine, procede de synthese, et medicaments renfermant ces derives |
-
2001
- 2001-10-12 FR FR0113209A patent/FR2830863B1/fr not_active Expired - Fee Related
-
2002
- 2002-10-14 ES ES02795314T patent/ES2326115T3/es not_active Expired - Lifetime
- 2002-10-14 JP JP2003534397A patent/JP2005508350A/ja active Pending
- 2002-10-14 DK DK02795314T patent/DK1461319T3/da active
- 2002-10-14 AT AT02795314T patent/ATE430134T1/de not_active IP Right Cessation
- 2002-10-14 US US10/492,088 patent/US7064133B2/en not_active Expired - Fee Related
- 2002-10-14 DE DE60232186T patent/DE60232186D1/de not_active Expired - Lifetime
- 2002-10-14 WO PCT/FR2002/003512 patent/WO2003031413A1/fr not_active Ceased
- 2002-10-14 EP EP02795314A patent/EP1461319B1/fr not_active Expired - Lifetime
- 2002-10-14 IL IL16132002A patent/IL161320A0/xx unknown
-
2004
- 2004-04-07 IL IL161320A patent/IL161320A/en not_active IP Right Cessation
-
2006
- 2006-03-01 US US11/364,329 patent/US20060148849A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20060148849A1 (en) | 2006-07-06 |
| EP1461319A1 (fr) | 2004-09-29 |
| FR2830863A1 (fr) | 2003-04-18 |
| ATE430134T1 (de) | 2009-05-15 |
| US7064133B2 (en) | 2006-06-20 |
| IL161320A (en) | 2009-09-01 |
| DK1461319T3 (da) | 2009-08-03 |
| FR2830863B1 (fr) | 2004-01-30 |
| WO2003031413A1 (fr) | 2003-04-17 |
| EP1461319B1 (fr) | 2009-04-29 |
| US20040259911A1 (en) | 2004-12-23 |
| IL161320A0 (en) | 2004-09-27 |
| ES2326115T3 (es) | 2009-10-01 |
| DE60232186D1 (de) | 2009-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2286385C (fr) | Derives de quinoleines en tant qu'inhibiteurs de la vih integrase | |
| JP6629218B2 (ja) | N−ベンジルトリプタンスリン誘導体、ならびにその調製方法および利用 | |
| JP2013519674A (ja) | ベツリンの誘導体 | |
| JPH0586391B2 (enExample) | ||
| JP2016535788A5 (enExample) | ||
| WO2010010149A1 (en) | Styrylquinolines, their process of preparation and their therapeutic uses | |
| CA3124852A1 (en) | Indanone derivatives, pharmaceutically acceptable salts or optical isomers thereof, preparation method for same, and pharmaceutical compositions containing same as active ingredient for preventing or treating viral diseases | |
| WO2021176367A1 (en) | Inhibitors of human immunodeficiency virus replication | |
| JP2005508350A (ja) | キノリン誘導体、合成法およびこれらの誘導体を含有する薬剤 | |
| EP3611158B1 (en) | 1,3-di-oxo-indene derivative, pharmaceutically acceptable salt or optical isomer thereof, preparation method thereof, and pharmaceutical composition containing same as an antiviral, active ingredient | |
| CN103965163B (zh) | 一种含嘧啶环的喹诺酮类衍生物及其制备方法和用途 | |
| US20060094755A1 (en) | Novel quinoline-based metal chelators as antiviral agents | |
| JP2004513971A (ja) | プロテアーゼ・インヒビタ及びその医薬的使用方法 | |
| JP4482883B2 (ja) | 抗ウイルス作用を有する化合物およびその配合剤 | |
| CN109369623A (zh) | 一种取代1,2,3三氮唑类二芳基嘧啶衍生物及其制备方法与应用 | |
| CN102212032B (zh) | 一种5-羟基喹诺酮类衍生物及其制备方法和用途 | |
| CN108689958B (zh) | 一种含有肼基的吲哚胺2,3-双加氧化酶抑制剂 | |
| CN104876880A (zh) | 一种二芳醚类衍生物及其制备方法和应用 | |
| US20060063938A1 (en) | Compounds to treat hiv infection and aids | |
| CN115403625B (zh) | S-DACOs类非核苷类逆转录酶抑制剂衍生物及其用途 | |
| CN119528841B (zh) | 衣壳抑制剂及其制备方法和用途 | |
| CN109810044A (zh) | 一种具有hiv-1整合酶抑制活性的化合物及其制备和应用 | |
| EP2149557A1 (en) | Styrylquinolines, their process of preparation and their therapeutic uses | |
| Ferro et al. | Synthesis of new pyridazine derivatives as potential anti-HIV-1 agents | |
| JP7076845B2 (ja) | 3,4-ジヒドロチエノ[3,2-d]ピリミジン系化合物の結晶形およびその調製方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20050601 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20050601 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050729 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050729 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090421 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20091013 |