CN1032539A - 取代的噻吩并咪唑衍生物，它们的制备方法，含有它们的药物制剂以及它们作为胃酸分泌抑制剂的应用 - Google Patents
取代的噻吩并咪唑衍生物，它们的制备方法，含有它们的药物制剂以及它们作为胃酸分泌抑制剂的应用 Download PDFInfo
- Publication number
- CN1032539A CN1032539A CN88104890A CN88104890A CN1032539A CN 1032539 A CN1032539 A CN 1032539A CN 88104890 A CN88104890 A CN 88104890A CN 88104890 A CN88104890 A CN 88104890A CN 1032539 A CN1032539 A CN 1032539A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- group
- compound
- formula
- thieno
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 4
- JCZAVVUIFWZMQI-UHFFFAOYSA-N 1h-thieno[2,3-d]imidazole Chemical class N1C=NC2=C1C=CS2 JCZAVVUIFWZMQI-UHFFFAOYSA-N 0.000 title description 12
- 230000027119 gastric acid secretion Effects 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 239000003814 drug Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 150000002460 imidazoles Chemical class 0.000 claims description 32
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
- -1 (C 1-C 6)-alkyl-carbonyl oxygen Chemical compound 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 239000011737 fluorine Substances 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 17
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 17
- 230000035479 physiological effects, processes and functions Effects 0.000 claims description 16
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 10
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- QFXZANXYUCUTQH-UHFFFAOYSA-N ethynol Chemical group OC#C QFXZANXYUCUTQH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 238000005991 sulfenylation reaction Methods 0.000 claims description 2
- RFYFAGLECGBRPW-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=C(C=CC=C1)N(C)NC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)OC1=C(C=CC=C1)N(C)NC1=CC=CC=C1 RFYFAGLECGBRPW-UHFFFAOYSA-N 0.000 claims 1
- 125000003302 alkenyloxy group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 238000002425 crystallisation Methods 0.000 description 33
- 230000008025 crystallization Effects 0.000 description 33
- 239000000047 product Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000000605 extraction Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 8
- GKRYOTUQPZKDFB-UHFFFAOYSA-N C1=CC=CC=C1C(=O)OO.[Cl] Chemical compound C1=CC=CC=C1C(=O)OO.[Cl] GKRYOTUQPZKDFB-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 238000013019 agitation Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- JITVQETUYJVBKJ-UHFFFAOYSA-N 1,3-dihydrothieno[3,4-d]imidazole-2-thione Chemical class S1C=C2NC(=S)NC2=C1 JITVQETUYJVBKJ-UHFFFAOYSA-N 0.000 description 4
- AQSRRZGQRFFFGS-UHFFFAOYSA-N 2-methylpyridin-3-ol Chemical compound CC1=NC=CC=C1O AQSRRZGQRFFFGS-UHFFFAOYSA-N 0.000 description 4
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- GALRLPSHWHSQAX-UHFFFAOYSA-N 3-bromo-2-methyl-4-nitropyridine Chemical compound BrC=1C(=NC=CC=1[N+](=O)[O-])C GALRLPSHWHSQAX-UHFFFAOYSA-N 0.000 description 3
- DEMKNLXJQNYAFY-UHFFFAOYSA-N 5-chloro-2-methylpyridine Chemical compound CC1=CC=C(Cl)C=N1 DEMKNLXJQNYAFY-UHFFFAOYSA-N 0.000 description 3
- UENBBJXGCWILBM-UHFFFAOYSA-N 6-methylpyridin-3-amine Chemical compound CC1=CC=C(N)C=N1 UENBBJXGCWILBM-UHFFFAOYSA-N 0.000 description 3
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000012062 aqueous buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 239000003792 electrolyte Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 238000009377 nuclear transmutation Methods 0.000 description 3
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- ONEDJPAUQCOCCJ-UHFFFAOYSA-N (5-chloro-4-methoxypyridin-2-yl)methanol Chemical compound COC1=CC(CO)=NC=C1Cl ONEDJPAUQCOCCJ-UHFFFAOYSA-N 0.000 description 2
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 2
- AIPWPTPHMIYYOX-UHFFFAOYSA-N 3-bromo-2-methylpyridine Chemical compound CC1=NC=CC=C1Br AIPWPTPHMIYYOX-UHFFFAOYSA-N 0.000 description 2
- MPZBNXOIDZWMKL-UHFFFAOYSA-N 5-bromo-2-methyl-4-nitropyridine Chemical compound CC1=CC([N+]([O-])=O)=C(Br)C=N1 MPZBNXOIDZWMKL-UHFFFAOYSA-N 0.000 description 2
- OFKWIQJLYCKDNY-UHFFFAOYSA-N 5-bromo-2-methylpyridine Chemical compound CC1=CC=C(Br)C=N1 OFKWIQJLYCKDNY-UHFFFAOYSA-N 0.000 description 2
- DHLUJPLHLZJUBW-UHFFFAOYSA-N 6-methylpyridin-3-ol Chemical compound CC1=CC=C(O)C=N1 DHLUJPLHLZJUBW-UHFFFAOYSA-N 0.000 description 2
- RZOKQIPOABEQAM-UHFFFAOYSA-N 6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=N1 RZOKQIPOABEQAM-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052793 cadmium Inorganic materials 0.000 description 2
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000010931 ester hydrolysis Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- BFLIRPGEXPAQAW-UHFFFAOYSA-N thiophene-2,3-diamine Chemical compound NC=1C=CSC=1N BFLIRPGEXPAQAW-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 1
- BKTHTLOKUUJKDF-UHFFFAOYSA-N (3,4-dimethoxypyridin-2-yl)methanol Chemical compound COC1=CC=NC(CO)=C1OC BKTHTLOKUUJKDF-UHFFFAOYSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- INOGLHRUEYDAHX-UHFFFAOYSA-N 1-chlorobenzotriazole Chemical compound C1=CC=C2N(Cl)N=NC2=C1 INOGLHRUEYDAHX-UHFFFAOYSA-N 0.000 description 1
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
- YYRIKJFWBIEEDH-UHFFFAOYSA-N 2-(chloromethyl)-3,4-dimethoxypyridine;hydrochloride Chemical compound [Cl-].COC1=CC=[NH+]C(CCl)=C1OC YYRIKJFWBIEEDH-UHFFFAOYSA-N 0.000 description 1
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
- CDDROKSILCNBFL-UHFFFAOYSA-N 2-[(3,4-dimethoxypyridin-2-yl)methylsulfanyl]-1h-thieno[3,4-d]imidazole Chemical class COC1=CC=NC(CSC=2NC3=CSC=C3N=2)=C1OC CDDROKSILCNBFL-UHFFFAOYSA-N 0.000 description 1
- AVOAHNTUYBICCS-UHFFFAOYSA-N 2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1h-thieno[3,4-d]imidazole Chemical class COC1=CC=NC(C[S+]([O-])C=2NC3=CSC=C3N=2)=C1OC AVOAHNTUYBICCS-UHFFFAOYSA-N 0.000 description 1
- WCPMUSGJIRECSP-UHFFFAOYSA-N 2-[(3-fluoropyridin-2-yl)methylsulfinyl]-1h-thieno[3,4-d]imidazole Chemical class N=1C2=CSC=C2NC=1[S+]([O-])CC1=NC=CC=C1F WCPMUSGJIRECSP-UHFFFAOYSA-N 0.000 description 1
- RYOOHIUJEJZCFT-UHFFFAOYSA-N 2-[2-(diethylamino)ethylamino]-2-phenylacetic acid 3-methylbutyl ester Chemical compound CCN(CC)CCNC(C(=O)OCCC(C)C)C1=CC=CC=C1 RYOOHIUJEJZCFT-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- WDRFYIPWHMGQPN-UHFFFAOYSA-N 2-chloroisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Cl)C(=O)C2=C1 WDRFYIPWHMGQPN-UHFFFAOYSA-N 0.000 description 1
- HPFRZWNATIXQRX-UHFFFAOYSA-N 2-methyl-5-(trifluoromethoxy)pyridine Chemical compound CC1=CC=C(OC(F)(F)F)C=N1 HPFRZWNATIXQRX-UHFFFAOYSA-N 0.000 description 1
- GADHYUUHHGADGT-UHFFFAOYSA-N 2-nitrothiophen-3-amine Chemical compound NC=1C=CSC=1[N+]([O-])=O GADHYUUHHGADGT-UHFFFAOYSA-N 0.000 description 1
- UMVFRRJTPKYVAY-UHFFFAOYSA-N 3,4-dimethoxy-2-methyl-1-oxidopyridin-1-ium Chemical class COC1=CC=[N+]([O-])C(C)=C1OC UMVFRRJTPKYVAY-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- IRIHSZDBTACXCT-UHFFFAOYSA-N 3-fluoro-2-methylpyridine Chemical compound CC1=NC=CC=C1F IRIHSZDBTACXCT-UHFFFAOYSA-N 0.000 description 1
- ZXBHWFBOEKPCCN-UHFFFAOYSA-N 5-bromo-2-methyl-4-nitro-1-oxidopyridin-1-ium Chemical compound CC1=CC([N+]([O-])=O)=C(Br)C=[N+]1[O-] ZXBHWFBOEKPCCN-UHFFFAOYSA-N 0.000 description 1
- NNDAYCLMPFWHFS-UHFFFAOYSA-N 5-chloro-2-(chloromethyl)-4-methoxypyridine;hydrochloride Chemical compound Cl.COC1=CC(CCl)=NC=C1Cl NNDAYCLMPFWHFS-UHFFFAOYSA-N 0.000 description 1
- WVRFCQAUQGMHBV-UHFFFAOYSA-N 5-fluoro-2-methyl-4-nitropyridine Chemical compound CC1=CC([N+]([O-])=O)=C(F)C=N1 WVRFCQAUQGMHBV-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- CAVZBWFUMSXZFB-LJWNLINESA-N Amogastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)OC(C)(C)CC)C(N)=O)C1=CC=CC=C1 CAVZBWFUMSXZFB-LJWNLINESA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 208000012639 Balance disease Diseases 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 1
- 241000754688 Cercaria Species 0.000 description 1
- 241000242722 Cestoda Species 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 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
- 208000004232 Enteritis Diseases 0.000 description 1
- 208000007882 Gastritis 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
- 241000241125 Gryllotalpa gryllotalpa Species 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 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
- FSNCEEGOMTYXKY-JTQLQIEISA-N Lycoperodine 1 Natural products N1C2=CC=CC=C2C2=C1CN[C@H](C(=O)O)C2 FSNCEEGOMTYXKY-JTQLQIEISA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- DUDKAZCAISNGQN-UHFFFAOYSA-N Oxyphencyclimine Chemical compound CN1CCCN=C1COC(=O)C(O)(C=1C=CC=CC=1)C1CCCCC1 DUDKAZCAISNGQN-UHFFFAOYSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 241000255129 Phlebotominae Species 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 241000242678 Schistosoma Species 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 244000062793 Sorghum vulgare Species 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 241000255632 Tabanus atratus Species 0.000 description 1
- SWEDAZLCYJDAGW-UHFFFAOYSA-N Thiophene-2-thiol Chemical compound SC1=CC=CS1 SWEDAZLCYJDAGW-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 150000001356 alkyl thiols Chemical class 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 108700042255 amogastrin Proteins 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- JGTJANXYSNVLMQ-UHFFFAOYSA-N bietamiverine Chemical compound C=1C=CC=CC=1C(C(=O)OCCN(CC)CC)N1CCCCC1 JGTJANXYSNVLMQ-UHFFFAOYSA-N 0.000 description 1
- 229950005940 bietamiverine Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 150000001621 bismuth Chemical class 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960005242 camylofin Drugs 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
- 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229950010338 fencarbamide Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 150000002221 fluorine Chemical class 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000005291 haloalkenyloxy group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
- 229960004705 kojic acid Drugs 0.000 description 1
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- KJEDPJABIHESQZ-UHFFFAOYSA-N methyl 1H-thieno[2,3-d]imidazole-5-carboxylate Chemical class COC(=O)C1=CC2=C(N=CN2)S1 KJEDPJABIHESQZ-UHFFFAOYSA-N 0.000 description 1
- 235000019713 millet Nutrition 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 150000002976 peresters Chemical class 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical class OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 1
- 229960004633 pirenzepine Drugs 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 235000019394 potassium persulphate Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- BZGIPVGCJGXQTA-UHFFFAOYSA-N s-[2-(diethylamino)ethyl] n,n-diphenylcarbamothioate Chemical compound C=1C=CC=CC=1N(C(=O)SCCN(CC)CC)C1=CC=CC=C1 BZGIPVGCJGXQTA-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- NYCVSSWORUBFET-UHFFFAOYSA-M sodium;bromite Chemical compound [Na+].[O-]Br=O NYCVSSWORUBFET-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 229950009390 symclosene Drugs 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
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/195—Antibiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Fodder In General (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3725940.7 | 1987-08-05 | ||
| DE19873725940 DE3725940A1 (de) | 1987-08-05 | 1987-08-05 | Streptogramin b-metallkomplexe, ihre herstellung und verwendung in der tierernaehrung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1032539A true CN1032539A (zh) | 1989-04-26 |
Family
ID=6333086
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN88104890A Pending CN1032539A (zh) | 1987-08-05 | 1988-08-05 | 取代的噻吩并咪唑衍生物，它们的制备方法，含有它们的药物制剂以及它们作为胃酸分泌抑制剂的应用 |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0302407A3 (enExample) |
| JP (1) | JPS6450898A (enExample) |
| KR (1) | KR890003803A (enExample) |
| CN (1) | CN1032539A (enExample) |
| AU (1) | AU2042288A (enExample) |
| CS (1) | CS545888A2 (enExample) |
| DD (1) | DD272466A5 (enExample) |
| DE (1) | DE3725940A1 (enExample) |
| DK (1) | DK436488A (enExample) |
| HU (1) | HUT48643A (enExample) |
| IL (1) | IL87356A0 (enExample) |
| IN (1) | IN166306B (enExample) |
| ZA (1) | ZA885681B (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5118665A (en) * | 1990-02-09 | 1992-06-02 | Procyte Corporation | Anti-oxidative and anti-inflammatory metal:peptide complexes and uses thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52151191A (en) * | 1976-06-10 | 1977-12-15 | Sanraku Inc | Novel antibiotics neoviridogriseins and their preparation |
-
1987
- 1987-06-23 IN IN191/BOM/87A patent/IN166306B/en unknown
- 1987-08-05 DE DE19873725940 patent/DE3725940A1/de not_active Withdrawn
-
1988
- 1988-07-29 EP EP88112339A patent/EP0302407A3/de not_active Withdrawn
- 1988-08-03 ZA ZA885681A patent/ZA885681B/xx unknown
- 1988-08-03 DD DD88318651A patent/DD272466A5/de not_active IP Right Cessation
- 1988-08-04 CS CS885458A patent/CS545888A2/cs unknown
- 1988-08-04 AU AU20422/88A patent/AU2042288A/en not_active Abandoned
- 1988-08-04 JP JP63193574A patent/JPS6450898A/ja active Pending
- 1988-08-04 KR KR1019880009935A patent/KR890003803A/ko not_active Withdrawn
- 1988-08-04 HU HU884088A patent/HUT48643A/hu unknown
- 1988-08-04 IL IL87356A patent/IL87356A0/xx unknown
- 1988-08-04 DK DK436488A patent/DK436488A/da not_active Application Discontinuation
- 1988-08-05 CN CN88104890A patent/CN1032539A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0302407A3 (de) | 1990-07-04 |
| DD272466A5 (de) | 1989-10-11 |
| EP0302407A2 (de) | 1989-02-08 |
| ZA885681B (en) | 1989-04-26 |
| DK436488D0 (da) | 1988-08-04 |
| DK436488A (da) | 1989-02-06 |
| HUT48643A (en) | 1989-06-28 |
| IN166306B (enExample) | 1990-04-07 |
| IL87356A0 (en) | 1989-01-31 |
| JPS6450898A (en) | 1989-02-27 |
| AU2042288A (en) | 1989-04-20 |
| DE3725940A1 (de) | 1989-02-16 |
| KR890003803A (ko) | 1989-04-18 |
| CS545888A2 (en) | 1990-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1029231C (zh) | 三唑类抗霉菌剂的制备方法 | |
| CN1020608C (zh) | 制备5-(6-咪唑并[1，2-a]吡啶基)吡啶衍生物 | |
| CN1036920C (zh) | 含杂环碳酸衍生物 | |
| CN1152022C (zh) | α-取代的嘧啶-硫代烷基和烷基醚化合物 | |
| CN1045781A (zh) | N-(3-羟基-4-哌啶基)(二氢苯并呋喃，二氢-2h-苯并吡喃或二氢苯并二英)甲酰胺衍生物 | |
| CN1443165A (zh) | 环戊二烯并吲哚、含有这类化合物的组合物及治疗方法 | |
| CN1294577A (zh) | 钾通道抑制剂 | |
| CN1374953A (zh) | 含氮的6－员芳香环化合物 | |
| CN1035508A (zh) | 新的取代的喹啉衍生物的制备方法 | |
| CN1032361C (zh) | 咪唑并哒嗪化合物的制备方法 | |
| CN1067889A (zh) | 取代的n-(1-烷基-3-羟基-4-哌啶基)苯甲酰胺的制备方法 | |
| CN101052634A (zh) | 作为vegf受体激酶抑制剂的邻氨基苯甲酰胺吡啶脲 | |
| CN1289483C (zh) | 甘氨酰胺的杂环衍生物及其医药用途 | |
| CN1042632C (zh) | 吡啶酮羧酸衍生物、制备它们的中间体及药物组合物 | |
| CN1020900C (zh) | 制备新的取代n-(3-羟基-4-哌啶基)苯甲酰胺的方法 | |
| CN1503797A (zh) | 吡啶并嘧啶或二氮杂萘衍生物 | |
| CN1013445B (zh) | 苯并咪唑衍生物的制备方法 | |
| CN1032439A (zh) | 一种血小板活化因子拮抗剂的制备方法 | |
| CN86108133A (zh) | 喹诺酮强心兴奋剂 | |
| CN1082029A (zh) | 联苯甲基取代的吡啶酮 | |
| CN1168716C (zh) | 光学活性四氢苯并吲哚衍生物 | |
| CN86102398A (zh) | 取代苯并咪唑衍生物的制备方法 | |
| CN87107226A (zh) | 内酰胺衍生物及其制备 | |
| CN1058015A (zh) | 苯甲酸衍生物 | |
| CN1032539A (zh) | 取代的噻吩并咪唑衍生物，它们的制备方法，含有它们的药物制剂以及它们作为胃酸分泌抑制剂的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination |