NO329667B1 - 1-fenyl-2-(pyridyl eller tienyl)-substituerte benzimidazolderivater, farmasoytiske preparater som inneholder forbindelsene og anvendelse av disse for fremstilling av legemidler benyttet for behandling av immunologiske sykdommer - Google Patents
1-fenyl-2-(pyridyl eller tienyl)-substituerte benzimidazolderivater, farmasoytiske preparater som inneholder forbindelsene og anvendelse av disse for fremstilling av legemidler benyttet for behandling av immunologiske sykdommer Download PDFInfo
- Publication number
- NO329667B1 NO329667B1 NO20043841A NO20043841A NO329667B1 NO 329667 B1 NO329667 B1 NO 329667B1 NO 20043841 A NO20043841 A NO 20043841A NO 20043841 A NO20043841 A NO 20043841A NO 329667 B1 NO329667 B1 NO 329667B1
- Authority
- NO
- Norway
- Prior art keywords
- oxy
- benzimidazol
- phenyl
- thienyl
- acid
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 29
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title claims abstract description 22
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 title claims description 50
- 125000004076 pyridyl group Chemical group 0.000 title claims description 4
- 125000001544 thienyl group Chemical group 0.000 title claims description 4
- 239000003814 drug Substances 0.000 title abstract description 11
- 208000026278 immune system disease Diseases 0.000 title abstract description 7
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract description 5
- 229940079593 drug Drugs 0.000 title description 7
- 239000008194 pharmaceutical composition Chemical class 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 6
- 150000001556 benzimidazoles Chemical class 0.000 claims description 34
- -1 6-[[1-phenyl-2-(3-thienyl)-1H-benzimidazol-6-yl]oxy]hexanoic acid 6-[[1-(4-fluorophenyl)-2-(3-thienyl)-1H-benzimidazol -6-yl]oxy]hexanoic acid Chemical compound 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 16
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 15
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 15
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 10
- 208000023275 Autoimmune disease Diseases 0.000 claims description 9
- 208000035473 Communicable disease Diseases 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- JFGRCXYDFKTCJV-UHFFFAOYSA-N 5-[3-(4-fluorophenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxypentanoic acid Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCC(=O)O)=CC=C2N=C1C=1C=CSC=1 JFGRCXYDFKTCJV-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- QKKGHFKYCAFNIE-UHFFFAOYSA-N 4-[3-(4-methylphenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxybutanoic acid Chemical compound C1=CC(C)=CC=C1N1C2=CC(OCCCC(O)=O)=CC=C2N=C1C1=CC=CN=C1 QKKGHFKYCAFNIE-UHFFFAOYSA-N 0.000 claims description 3
- VGBCVMRXSFEWJF-UHFFFAOYSA-N 6-(3-phenyl-2-pyridin-3-ylbenzimidazol-5-yl)oxyhexanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCCCC(=O)O)=CC=C2N=C1C1=CC=CN=C1 VGBCVMRXSFEWJF-UHFFFAOYSA-N 0.000 claims description 3
- YQTAXLNBLDFVGQ-UHFFFAOYSA-N 6-[3-(4-methylphenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxyhexanoic acid Chemical compound C1=CC(C)=CC=C1N1C2=CC(OCCCCCC(O)=O)=CC=C2N=C1C1=CC=CN=C1 YQTAXLNBLDFVGQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012876 carrier material Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- RAJZZBKNJIYMHR-UHFFFAOYSA-N 5-(3-phenyl-2-thiophen-3-ylbenzimidazol-5-yl)oxypentanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCCC(=O)O)=CC=C2N=C1C=1C=CSC=1 RAJZZBKNJIYMHR-UHFFFAOYSA-N 0.000 claims description 2
- BWVRFTRQLNIZPB-UHFFFAOYSA-N 5-[3-(4-fluorophenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxypentanoic acid Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCC(=O)O)=CC=C2N=C1C1=CC=CN=C1 BWVRFTRQLNIZPB-UHFFFAOYSA-N 0.000 claims description 2
- JEYRNGVELJSDMF-UHFFFAOYSA-N 5-[3-(4-methylphenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxypentanoic acid Chemical compound C1=CC(C)=CC=C1N1C2=CC(OCCCCC(O)=O)=CC=C2N=C1C1=CSC=C1 JEYRNGVELJSDMF-UHFFFAOYSA-N 0.000 claims description 2
- GJQWVDITCAKBGR-UHFFFAOYSA-N 6-(3-phenyl-2-pyridin-4-ylbenzimidazol-5-yl)oxyhexanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCCCC(=O)O)=CC=C2N=C1C1=CC=NC=C1 GJQWVDITCAKBGR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 17
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 13
- 230000006724 microglial activation Effects 0.000 abstract description 12
- 230000001404 mediated effect Effects 0.000 abstract description 9
- 230000006806 disease prevention Effects 0.000 abstract 1
- 230000033228 biological regulation Effects 0.000 description 54
- 210000004027 cell Anatomy 0.000 description 37
- 150000001793 charged compounds Chemical class 0.000 description 35
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 35
- 239000000126 substance Substances 0.000 description 31
- 239000000243 solution Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 108010065805 Interleukin-12 Proteins 0.000 description 27
- 102000013462 Interleukin-12 Human genes 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 19
- NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 239000002158 endotoxin Substances 0.000 description 17
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 16
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 229920006008 lipopolysaccharide Polymers 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- 210000004556 brain Anatomy 0.000 description 10
- 238000005119 centrifugation Methods 0.000 description 10
- 229940117681 interleukin-12 Drugs 0.000 description 10
- 210000000274 microglia Anatomy 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000012894 fetal calf serum Substances 0.000 description 8
- HNBDRPTVWVGKBR-UHFFFAOYSA-N methyl pentanoate Chemical compound CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 8
- 210000001616 monocyte Anatomy 0.000 description 8
- HUPQYPMULVBQDL-UHFFFAOYSA-N pentanoic acid Chemical compound CCCCC(O)=O.CCCCC(O)=O HUPQYPMULVBQDL-UHFFFAOYSA-N 0.000 description 8
- 108700012920 TNF Proteins 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000002025 microglial effect Effects 0.000 description 7
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 6
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000012980 RPMI-1640 medium Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 206010040070 Septic Shock Diseases 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 210000000601 blood cell Anatomy 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- KYLVAMSNNZMHSX-UHFFFAOYSA-N methyl 6-bromohexanoate Chemical compound COC(=O)CCCCCBr KYLVAMSNNZMHSX-UHFFFAOYSA-N 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 108090000174 Interleukin-10 Proteins 0.000 description 5
- 102000003814 Interleukin-10 Human genes 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- RAVVJKCSZXAIQP-UHFFFAOYSA-N methyl 5-bromopentanoate Chemical compound COC(=O)CCCCBr RAVVJKCSZXAIQP-UHFFFAOYSA-N 0.000 description 5
- 201000006417 multiple sclerosis Diseases 0.000 description 5
- 210000000822 natural killer cell Anatomy 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 230000001960 triggered effect Effects 0.000 description 5
- FBKFDSUZBVDZIX-FFGDOFBPSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1h-indol-3-yl)propanoyl]amino]-5-[[1-[[(2s)-1-amino-4-meth Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NC(C)(C)C(=O)N[C@@H](CC=1C=CC(CP(O)(O)=O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=C(Cl)C=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)NC1(CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(C)=O)C1=CC=CC=C1 FBKFDSUZBVDZIX-FFGDOFBPSA-N 0.000 description 4
- MCNKCQILYFQWEJ-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-thiophen-3-ylbenzimidazol-5-ol Chemical compound C=1C=C(F)C=CC=1N1C2=CC(O)=CC=C2N=C1C=1C=CSC=1 MCNKCQILYFQWEJ-UHFFFAOYSA-N 0.000 description 4
- GDUHURCUDWFHRC-UHFFFAOYSA-N 3-phenyl-2-thiophen-3-ylbenzimidazol-5-ol Chemical compound C=1C=CC=CC=1N1C2=CC(O)=CC=C2N=C1C=1C=CSC=1 GDUHURCUDWFHRC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 206010008118 cerebral infarction Diseases 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000019734 interleukin-12 production Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000003959 neuroinflammation Effects 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000006433 tumor necrosis factor production Effects 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 3
- VJWUCSAURXOJRS-UHFFFAOYSA-N 3-phenyl-2-pyridin-3-ylbenzimidazol-5-ol Chemical compound C=1C=CC=CC=1N1C2=CC(O)=CC=C2N=C1C1=CC=CN=C1 VJWUCSAURXOJRS-UHFFFAOYSA-N 0.000 description 3
- QZVROQWRTFMJQM-UHFFFAOYSA-N 5-chloro-n-(4-fluorophenyl)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1=CC=C(F)C=C1 QZVROQWRTFMJQM-UHFFFAOYSA-N 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 206010044248 Toxic shock syndrome Diseases 0.000 description 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 125000003118 aryl group Chemical group 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
- 239000002775 capsule Substances 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000001684 chronic effect Effects 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
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000000432 density-gradient centrifugation Methods 0.000 description 3
- 208000002296 eclampsia Diseases 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 150000004679 hydroxides Chemical class 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- QAWFLJGZSZIZHO-UHFFFAOYSA-N methyl 4-bromobutanoate Chemical compound COC(=O)CCCBr QAWFLJGZSZIZHO-UHFFFAOYSA-N 0.000 description 3
- 210000003657 middle cerebral artery Anatomy 0.000 description 3
- HXEDESMOXGZERC-UHFFFAOYSA-N n-(4-fluorophenyl)-5-methoxy-2-nitroaniline Chemical compound COC1=CC=C([N+]([O-])=O)C(NC=2C=CC(F)=CC=2)=C1 HXEDESMOXGZERC-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 3
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical class C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- MPDKHDIOJJKLBX-UHFFFAOYSA-N 3-(4-methylanilino)-4-nitrophenol Chemical compound C1=CC(C)=CC=C1NC1=CC(O)=CC=C1[N+]([O-])=O MPDKHDIOJJKLBX-UHFFFAOYSA-N 0.000 description 2
- VVIKVNYJIWIGOW-UHFFFAOYSA-N 4-(3-phenyl-2-pyridin-3-ylbenzimidazol-5-yl)oxybutanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCC(=O)O)=CC=C2N=C1C1=CC=CN=C1 VVIKVNYJIWIGOW-UHFFFAOYSA-N 0.000 description 2
- LIMXVGLZUYBCBM-UHFFFAOYSA-N 6-[3-(4-methylphenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxyhexanoic acid Chemical compound C1=CC(C)=CC=C1N1C2=CC(OCCCCCC(O)=O)=CC=C2N=C1C1=CSC=C1 LIMXVGLZUYBCBM-UHFFFAOYSA-N 0.000 description 2
- JSNBWHBULTWHJV-UHFFFAOYSA-N 6-methoxy-1-phenyl-2-thiophen-3-ylbenzimidazole Chemical compound C=1C=CC=CC=1N1C2=CC(OC)=CC=C2N=C1C=1C=CSC=1 JSNBWHBULTWHJV-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 201000010374 Down Syndrome Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 238000008157 ELISA kit Methods 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
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- 241001465754 Metazoa Species 0.000 description 2
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010047620 Phytohemagglutinins Proteins 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- 102000029797 Prion Human genes 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 210000001642 activated microglia Anatomy 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001347 alkyl bromides Chemical class 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 208000002029 allergic contact dermatitis Diseases 0.000 description 2
- 238000011316 allogeneic transplantation Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-UHFFFAOYSA-N 0.000 description 2
- AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000005661 deetherification reaction Methods 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 2
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000002518 glial effect Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000031261 interleukin-10 production Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- HWBJJCMWRFJYTD-UHFFFAOYSA-N methyl 4-[3-(4-methylanilino)-4-nitrophenoxy]butanoate Chemical compound COC(=O)CCCOC1=CC=C([N+]([O-])=O)C(NC=2C=CC(C)=CC=2)=C1 HWBJJCMWRFJYTD-UHFFFAOYSA-N 0.000 description 2
- VVHZWSPCLQREHP-UHFFFAOYSA-N methyl 4-[3-(4-methylphenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxybutanoate Chemical compound C=1C=C(C)C=CC=1N1C2=CC(OCCCC(=O)OC)=CC=C2N=C1C1=CC=CN=C1 VVHZWSPCLQREHP-UHFFFAOYSA-N 0.000 description 2
- PYXSLHMYBWEIJT-UHFFFAOYSA-N methyl 4-[3-(4-methylphenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxybutanoate Chemical compound C=1C=C(C)C=CC=1N1C2=CC(OCCCC(=O)OC)=CC=C2N=C1C=1C=CSC=1 PYXSLHMYBWEIJT-UHFFFAOYSA-N 0.000 description 2
- SBYHTCQFZMEEGD-UHFFFAOYSA-N methyl 4-[4-amino-3-(4-methylanilino)phenoxy]butanoate Chemical compound COC(=O)CCCOC1=CC=C(N)C(NC=2C=CC(C)=CC=2)=C1 SBYHTCQFZMEEGD-UHFFFAOYSA-N 0.000 description 2
- LUEOVSIBCNTFGS-UHFFFAOYSA-N methyl 5-[3-(4-methylanilino)-4-nitrophenoxy]pentanoate Chemical compound COC(=O)CCCCOC1=CC=C([N+]([O-])=O)C(NC=2C=CC(C)=CC=2)=C1 LUEOVSIBCNTFGS-UHFFFAOYSA-N 0.000 description 2
- CKESTYRBNJTBRR-UHFFFAOYSA-N methyl 5-[4-amino-3-(4-methylanilino)phenoxy]pentanoate Chemical compound COC(=O)CCCCOC1=CC=C(N)C(NC=2C=CC(C)=CC=2)=C1 CKESTYRBNJTBRR-UHFFFAOYSA-N 0.000 description 2
- KDTNNYSJDRNIFC-UHFFFAOYSA-N methyl 6-[3-(4-methylanilino)-4-nitrophenoxy]hexanoate Chemical compound COC(=O)CCCCCOC1=CC=C([N+]([O-])=O)C(NC=2C=CC(C)=CC=2)=C1 KDTNNYSJDRNIFC-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000007302 negative regulation of cytokine production Effects 0.000 description 2
- 208000018411 neoplasm of temporal lobe Diseases 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000003950 pathogenic mechanism Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000001991 pathophysiological effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000003408 phase transfer catalysis Methods 0.000 description 2
- 230000001885 phytohemagglutinin Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000000518 rheometry Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 201000000306 sarcoidosis Diseases 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 201000008914 temporal lobe epilepsy Diseases 0.000 description 2
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 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
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 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
- 238000012546 transfer Methods 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ZLGVZKQXZYQJSM-UHFFFAOYSA-N 1,2-diphenylbenzimidazole Chemical compound C1=CC=CC=C1C1=NC2=CC=CC=C2N1C1=CC=CC=C1 ZLGVZKQXZYQJSM-UHFFFAOYSA-N 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical class NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- GVKOHBDZQJYPIB-UHFFFAOYSA-N 1-(4-fluorophenyl)-6-methoxy-2-thiophen-3-ylbenzimidazole Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OC)=CC=C2N=C1C=1C=CSC=1 GVKOHBDZQJYPIB-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- NFCPRRWCTNLGSN-UHFFFAOYSA-N 2-n-phenylbenzene-1,2-diamine Chemical compound NC1=CC=CC=C1NC1=CC=CC=C1 NFCPRRWCTNLGSN-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- SBGHKYJYJJDINP-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-pyridin-3-ylbenzimidazol-5-ol Chemical compound C=1C=C(F)C=CC=1N1C2=CC(O)=CC=C2N=C1C1=CC=CN=C1 SBGHKYJYJJDINP-UHFFFAOYSA-N 0.000 description 1
- CSSGKHVRDGATJL-UHFFFAOYSA-N 3-fluoro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(F)=C1 CSSGKHVRDGATJL-UHFFFAOYSA-N 0.000 description 1
- 125000004839 3-methylpentylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])C([H])([H])[*:1])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OFHTZULTNPZRPN-UHFFFAOYSA-N 4-(3-phenyl-2-thiophen-3-ylbenzimidazol-5-yl)oxybutanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCC(=O)O)=CC=C2N=C1C=1C=CSC=1 OFHTZULTNPZRPN-UHFFFAOYSA-N 0.000 description 1
- TXUNAYOXUXLHDV-UHFFFAOYSA-N 4-[3-(4-methylphenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxybutanoic acid Chemical compound C1=CC(C)=CC=C1N1C2=CC(OCCCC(O)=O)=CC=C2N=C1C1=CSC=C1 TXUNAYOXUXLHDV-UHFFFAOYSA-N 0.000 description 1
- QVQSOXMXXFZAKU-UHFFFAOYSA-N 4-chloro-1,2-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1[N+]([O-])=O QVQSOXMXXFZAKU-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- CADHKBANACADRO-UHFFFAOYSA-N 4-methoxy-1-n-phenylbenzene-1,2-diamine Chemical compound NC1=CC(OC)=CC=C1NC1=CC=CC=C1 CADHKBANACADRO-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- ZZHXSNXPUKRPLC-UHFFFAOYSA-N 5-(3-phenyl-2-pyridin-3-ylbenzimidazol-5-yl)oxypentanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCCC(=O)O)=CC=C2N=C1C1=CC=CN=C1 ZZHXSNXPUKRPLC-UHFFFAOYSA-N 0.000 description 1
- 150000000565 5-membered heterocyclic compounds Chemical class 0.000 description 1
- BIZRIXVWLHXELH-UHFFFAOYSA-N 5-methoxy-2-nitro-n-phenylaniline Chemical compound COC1=CC=C([N+]([O-])=O)C(NC=2C=CC=CC=2)=C1 BIZRIXVWLHXELH-UHFFFAOYSA-N 0.000 description 1
- MNCJJYOUOAEPOU-UHFFFAOYSA-N 6-(3-phenyl-2-thiophen-3-ylbenzimidazol-5-yl)oxyhexanoic acid Chemical compound C=1C=CC=CC=1N1C2=CC(OCCCCCC(=O)O)=CC=C2N=C1C=1C=CSC=1 MNCJJYOUOAEPOU-UHFFFAOYSA-N 0.000 description 1
- GBXQDSHRKRHYBC-UHFFFAOYSA-N 6-[3-(4-fluorophenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxyhexanoic acid Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCCC(=O)O)=CC=C2N=C1C1=CC=CN=C1 GBXQDSHRKRHYBC-UHFFFAOYSA-N 0.000 description 1
- ARCSQRVLGKKYRZ-UHFFFAOYSA-N 6-[3-(4-fluorophenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxyhexanoic acid Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCCC(=O)O)=CC=C2N=C1C=1C=CSC=1 ARCSQRVLGKKYRZ-UHFFFAOYSA-N 0.000 description 1
- YWKIEZQTTSKDDB-UHFFFAOYSA-N 6-methoxy-1-phenyl-2-pyridin-3-ylbenzimidazole Chemical compound C=1C=CC=CC=1N1C2=CC(OC)=CC=C2N=C1C1=CC=CN=C1 YWKIEZQTTSKDDB-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 244000122871 Caryocar villosum Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001940 Massive Hepatic Necrosis Diseases 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
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- NVVGMIRCFUVBOB-UHFFFAOYSA-N acetic acid;iron Chemical compound [Fe].CC(O)=O NVVGMIRCFUVBOB-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000004996 alkyl benzenes Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000002431 aminoalkoxy group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000005002 aryl methyl group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- MXMZCLLIUQEKSN-UHFFFAOYSA-N benzimidazoline Chemical compound C1=CC=C2NCNC2=C1 MXMZCLLIUQEKSN-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 102000052620 human IL10 Human genes 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 238000011866 long-term treatment Methods 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- VMHULHPZXXJTRE-UHFFFAOYSA-N methyl 5-[3-(4-fluorophenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxypentanoate Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCC(=O)OC)=CC=C2N=C1C1=CC=CN=C1 VMHULHPZXXJTRE-UHFFFAOYSA-N 0.000 description 1
- OAGBXRIUKIYQIU-UHFFFAOYSA-N methyl 5-[3-(4-fluorophenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxypentanoate Chemical compound COC(=O)CCCCOC1=CC2=C(C=C1)N=C(N2C3=CC=C(C=C3)F)C4=CSC=C4 OAGBXRIUKIYQIU-UHFFFAOYSA-N 0.000 description 1
- NVMKYPLNBWHQPU-UHFFFAOYSA-N methyl 5-[3-(4-methylphenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxypentanoate Chemical compound C=1C=C(C)C=CC=1N1C2=CC(OCCCCC(=O)OC)=CC=C2N=C1C=1C=CSC=1 NVMKYPLNBWHQPU-UHFFFAOYSA-N 0.000 description 1
- STRQVTXRQPFOLC-UHFFFAOYSA-N methyl 6-[3-(4-fluorophenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxyhexanoate Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCCC(=O)OC)=CC=C2N=C1C1=CC=CN=C1 STRQVTXRQPFOLC-UHFFFAOYSA-N 0.000 description 1
- QQEASFQTFYVKPJ-UHFFFAOYSA-N methyl 6-[3-(4-fluorophenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxyhexanoate Chemical compound C=1C=C(F)C=CC=1N1C2=CC(OCCCCCC(=O)OC)=CC=C2N=C1C=1C=CSC=1 QQEASFQTFYVKPJ-UHFFFAOYSA-N 0.000 description 1
- COJXDRKAMPMOHV-UHFFFAOYSA-N methyl 6-[3-(4-methylphenyl)-2-pyridin-3-ylbenzimidazol-5-yl]oxyhexanoate Chemical compound C=1C=C(C)C=CC=1N1C2=CC(OCCCCCC(=O)OC)=CC=C2N=C1C1=CC=CN=C1 COJXDRKAMPMOHV-UHFFFAOYSA-N 0.000 description 1
- NIWAULOWDPYIPX-UHFFFAOYSA-N methyl 6-[3-(4-methylphenyl)-2-thiophen-3-ylbenzimidazol-5-yl]oxyhexanoate Chemical compound C=1C=C(C)C=CC=1N1C2=CC(OCCCCCC(=O)OC)=CC=C2N=C1C=1C=CSC=1 NIWAULOWDPYIPX-UHFFFAOYSA-N 0.000 description 1
- GWQIQASOPUMDLO-UHFFFAOYSA-N methyl 6-[4-amino-3-(4-methylanilino)phenoxy]hexanoate Chemical compound COC(=O)CCCCCOC1=CC=C(N)C(NC=2C=CC(C)=CC=2)=C1 GWQIQASOPUMDLO-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000001016 myotrophic effect Effects 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
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N ortho-diethylbenzene Natural products CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000002071 phenylalkoxy group Chemical group 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229940075065 polyvinyl acetate Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000005554 pyridyloxy group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Transplantation (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10207844A DE10207844A1 (de) | 2002-02-15 | 2002-02-15 | 1-Phenyl-2-heteroaryl-substituierte Benzimidazolderivate, deren Verwendung zur Herstellung von Arzneimitteln sowie diese Derivate enthaltende pharmazeutische Präparate |
PCT/EP2003/000462 WO2003068766A1 (de) | 2002-02-15 | 2003-01-17 | 1-phenyl-2-heteroaryl-substituierte benzimidazolderivate, deren verwendung zur herstellung von arzneimitteln zur behandlung von immunologischen erkrankungen |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20043841L NO20043841L (no) | 2004-11-12 |
NO329667B1 true NO329667B1 (no) | 2010-11-29 |
Family
ID=27674913
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20043841A NO329667B1 (no) | 2002-02-15 | 2004-09-14 | 1-fenyl-2-(pyridyl eller tienyl)-substituerte benzimidazolderivater, farmasoytiske preparater som inneholder forbindelsene og anvendelse av disse for fremstilling av legemidler benyttet for behandling av immunologiske sykdommer |
Country Status (30)
Country | Link |
---|---|
EP (1) | EP1474415B1 (el) |
JP (1) | JP4739675B2 (el) |
KR (1) | KR101027556B1 (el) |
CN (1) | CN1317274C (el) |
AR (1) | AR038492A1 (el) |
AT (1) | ATE517881T1 (el) |
AU (1) | AU2003205624B2 (el) |
BR (1) | BR0307723A (el) |
CA (1) | CA2475780C (el) |
CR (1) | CR7442A (el) |
CY (1) | CY1113230T1 (el) |
DE (1) | DE10207844A1 (el) |
DK (1) | DK1474415T3 (el) |
EC (1) | ECSP045296A (el) |
ES (1) | ES2369662T3 (el) |
IL (1) | IL163431A (el) |
MX (1) | MXPA04007949A (el) |
NO (1) | NO329667B1 (el) |
NZ (1) | NZ534660A (el) |
PE (1) | PE20030941A1 (el) |
PL (1) | PL216233B1 (el) |
PT (1) | PT1474415E (el) |
RS (1) | RS51831B (el) |
RU (1) | RU2325384C2 (el) |
SI (1) | SI1474415T1 (el) |
TW (1) | TWI328583B (el) |
UA (1) | UA81243C2 (el) |
UY (1) | UY27661A1 (el) |
WO (1) | WO2003068766A1 (el) |
ZA (1) | ZA200407381B (el) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003080580A2 (en) | 2002-03-27 | 2003-10-02 | Glaxo Group Limited | Quinoline derivatives and their use as 5-ht6 ligands |
SI1638551T1 (sl) * | 2003-05-19 | 2012-04-30 | Irm Llc | Imunosupresivne spojine in sestavki |
WO2014044611A1 (en) | 2012-09-20 | 2014-03-27 | Bayer Pharma Aktiengesellschaft | 1-aryl-2-heteroaryl benzimidazoles for the induction of neuronal regeneration |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4330959A1 (de) * | 1993-09-09 | 1995-03-16 | Schering Ag | Neue Benzimidazolderivate, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung |
US7115645B2 (en) * | 2000-01-14 | 2006-10-03 | Schering Aktiengesellschaft | 1,2 diarylbenzimidazoles and their pharmaceutical use |
SI1246808T1 (sl) | 2000-01-14 | 2011-12-30 | Bayer Pharma AG | 1-2 - diarilni benzimidazoli za zdravljenje bolezni povezanih z aktivacijo mikroglije |
DE10207843A1 (de) * | 2002-02-15 | 2003-09-04 | Schering Ag | Mikrolia-Inhibitoren zur Unterbrechung von Interleukin 12 und IFN-gamma vermittelten Immunreaktionen |
-
2002
- 2002-02-15 DE DE10207844A patent/DE10207844A1/de not_active Ceased
-
2003
- 2003-01-17 NZ NZ534660A patent/NZ534660A/en not_active IP Right Cessation
- 2003-01-17 RS YU71404A patent/RS51831B/en unknown
- 2003-01-17 AT AT03702464T patent/ATE517881T1/de active
- 2003-01-17 AU AU2003205624A patent/AU2003205624B2/en not_active Ceased
- 2003-01-17 CA CA2475780A patent/CA2475780C/en not_active Expired - Fee Related
- 2003-01-17 BR BR0307723-3A patent/BR0307723A/pt not_active IP Right Cessation
- 2003-01-17 WO PCT/EP2003/000462 patent/WO2003068766A1/de active Application Filing
- 2003-01-17 UA UA20040907405A patent/UA81243C2/uk unknown
- 2003-01-17 DK DK03702464.3T patent/DK1474415T3/da active
- 2003-01-17 KR KR1020047012576A patent/KR101027556B1/ko not_active IP Right Cessation
- 2003-01-17 CN CNB038039974A patent/CN1317274C/zh not_active Expired - Fee Related
- 2003-01-17 SI SI200332061T patent/SI1474415T1/sl unknown
- 2003-01-17 PL PL371269A patent/PL216233B1/pl unknown
- 2003-01-17 JP JP2003567893A patent/JP4739675B2/ja not_active Expired - Fee Related
- 2003-01-17 ES ES03702464T patent/ES2369662T3/es not_active Expired - Lifetime
- 2003-01-17 EP EP03702464A patent/EP1474415B1/de not_active Expired - Lifetime
- 2003-01-17 PT PT03702464T patent/PT1474415E/pt unknown
- 2003-01-17 MX MXPA04007949A patent/MXPA04007949A/es active IP Right Grant
- 2003-01-17 RU RU2004127678/04A patent/RU2325384C2/ru not_active IP Right Cessation
- 2003-01-31 PE PE2003000110A patent/PE20030941A1/es not_active Application Discontinuation
- 2003-02-11 UY UY27661A patent/UY27661A1/es not_active Application Discontinuation
- 2003-02-12 AR ARP030100437A patent/AR038492A1/es not_active Application Discontinuation
- 2003-02-14 TW TW092103073A patent/TWI328583B/zh not_active IP Right Cessation
-
2004
- 2004-08-10 IL IL163431A patent/IL163431A/en not_active IP Right Cessation
- 2004-09-01 CR CR7442A patent/CR7442A/es not_active Application Discontinuation
- 2004-09-14 NO NO20043841A patent/NO329667B1/no not_active IP Right Cessation
- 2004-09-14 EC EC2004005296A patent/ECSP045296A/es unknown
- 2004-09-14 ZA ZA2004/07381A patent/ZA200407381B/en unknown
-
2011
- 2011-10-26 CY CY20111101016T patent/CY1113230T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2704701B1 (en) | Compounds for inflammation and immune-related uses | |
JP2005516950A (ja) | 代謝型グルタミン酸受容体−5のヘテロアリール置換イミダゾールモジュレータ | |
TW201018667A (en) | Compounds for inflammation and immune-related uses | |
TW201026693A (en) | Compounds for inflammation and immune-related uses | |
US6855714B2 (en) | 1-alkyl-2-aryl-benzimidazole derivatives, their use for the production of pharmaceutical agents as well as pharmaceutical preparations that contain these derivatives | |
JP2006522128A (ja) | 代謝調節型グルタミン酸受容体−5のモジュレーターとしての4環イミダゾール誘導体 | |
US7196202B2 (en) | 1-aryl-2-N-, S- or O-substituted benzimidazole derivatives, their use for the production of pharmaceutical agents as well as pharmaceutical preparations that contain these derivatives | |
JP2004530731A (ja) | 1−アルキル−2−アリール−ベンズイミダゾール誘導体、医薬製剤の製造のためへのそれらの使用、及びそれらの誘導体を含む医薬製剤 | |
US7683081B2 (en) | 1-phenyl-2-heteroaryl-substituted benzimidazole derivatives, their use for the production of pharmaceutical agents as well as pharmaceutical preparations that contain these derivatives | |
JP6089104B2 (ja) | アリールエチニル誘導体 | |
NO329667B1 (no) | 1-fenyl-2-(pyridyl eller tienyl)-substituerte benzimidazolderivater, farmasoytiske preparater som inneholder forbindelsene og anvendelse av disse for fremstilling av legemidler benyttet for behandling av immunologiske sykdommer | |
JP4351042B2 (ja) | 小グリア細胞−活性化−関連疾患、例えば炎症、アレルギー感染又は自己免疫疾患を処理するためのベンズイミダゾール誘導体類 | |
AU2016232978B2 (en) | Compositions for the treatment of fibrosis and fibrosis-related conditions | |
CA2853485A1 (en) | Compounds for inflammation and immune-related uses | |
WO2012064808A1 (en) | Tetrazolyl - tetrahydropyridine compounds for inflammation and immune - related uses |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: BAYER INTELLECTUAL PROPERTY GMBH, DE |
|
MM1K | Lapsed by not paying the annual fees |