RU2026293C1 - Способ получения производного имидазола - Google Patents
Способ получения производного имидазола Download PDFInfo
- Publication number
- RU2026293C1 RU2026293C1 SU904830916A SU4830916A RU2026293C1 RU 2026293 C1 RU2026293 C1 RU 2026293C1 SU 904830916 A SU904830916 A SU 904830916A SU 4830916 A SU4830916 A SU 4830916A RU 2026293 C1 RU2026293 C1 RU 2026293C1
- Authority
- RU
- Russia
- Prior art keywords
- solution
- mmol
- mixture
- added
- imidazole
- Prior art date
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- 150000002460 imidazoles Chemical class 0.000 title claims description 19
- 238000000034 method Methods 0.000 title abstract description 9
- 230000015572 biosynthetic process Effects 0.000 title abstract 2
- 238000003786 synthesis reaction Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical compound SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 3
- -1 C 1 - C 6 alkyl Chemical group 0.000 claims description 40
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 19
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 230000000767 anti-ulcer Effects 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- 150000004820 halides Chemical class 0.000 abstract 1
- 230000001988 toxicity Effects 0.000 abstract 1
- 231100000419 toxicity Toxicity 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 92
- 239000000243 solution Substances 0.000 description 81
- 239000000203 mixture Substances 0.000 description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 44
- 238000001816 cooling Methods 0.000 description 44
- 239000007864 aqueous solution Substances 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 238000005160 1H NMR spectroscopy Methods 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 229910000029 sodium carbonate Inorganic materials 0.000 description 22
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- 230000002401 inhibitory effect Effects 0.000 description 15
- 239000012280 lithium aluminium hydride Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000004821 distillation Methods 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 10
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 8
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000012258 stirred mixture Substances 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000003699 antiulcer agent Substances 0.000 description 6
- UNTBPXHCXVWYOI-UHFFFAOYSA-O azanium;oxido(dioxo)vanadium Chemical compound [NH4+].[O-][V](=O)=O UNTBPXHCXVWYOI-UHFFFAOYSA-O 0.000 description 6
- 235000019445 benzyl alcohol Nutrition 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 239000001103 potassium chloride Substances 0.000 description 5
- 235000011164 potassium chloride Nutrition 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229910052731 fluorine Chemical group 0.000 description 4
- 239000011737 fluorine Chemical group 0.000 description 4
- 210000004051 gastric juice Anatomy 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- NNCHIBLRHKCJIZ-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinylmethyl)-n-(2-methoxyethyl)aniline Chemical compound COCCNC1=CC=CC=C1CS(=O)C1=NC=CN1 NNCHIBLRHKCJIZ-UHFFFAOYSA-N 0.000 description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 0 C(CC1=*NC=CC1)C1NC1 Chemical compound C(CC1=*NC=CC1)C1NC1 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
- 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 3
- 238000000746 purification Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- MMXFYUFHHADFOY-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanylmethyl)-4-methoxy-n-(2-methoxyethyl)-3,5-dimethylaniline Chemical compound COCCNC1=CC(C)=C(OC)C(C)=C1CSC1=NC=CN1 MMXFYUFHHADFOY-UHFFFAOYSA-N 0.000 description 2
- PPVWGCMMGXJKJV-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanylmethyl)-n-(2-methoxyethyl)-4-methylaniline Chemical compound COCCNC1=CC=C(C)C=C1CSC1=NC=CN1 PPVWGCMMGXJKJV-UHFFFAOYSA-N 0.000 description 2
- HSUQOPZGBNMPCL-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanylmethyl)-n-(2-methoxyethyl)aniline Chemical compound COCCNC1=CC=CC=C1CSC1=NC=CN1 HSUQOPZGBNMPCL-UHFFFAOYSA-N 0.000 description 2
- SIQVKSCEPYOVHZ-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanylmethyl)-n-(2-propan-2-yloxyethyl)aniline Chemical compound CC(C)OCCNC1=CC=CC=C1CSC1=NC=CN1 SIQVKSCEPYOVHZ-UHFFFAOYSA-N 0.000 description 2
- ZATRXKMFRXTDBS-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinylmethyl)-4-methoxy-n-(2-methoxyethyl)-3,5-dimethylaniline Chemical compound COCCNC1=CC(C)=C(OC)C(C)=C1CS(=O)C1=NC=CN1 ZATRXKMFRXTDBS-UHFFFAOYSA-N 0.000 description 2
- BNOUNCMFJUOMJQ-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinylmethyl)-n-(2-methoxyethyl)-3-methylaniline Chemical compound COCCNC1=CC=CC(C)=C1CS(=O)C1=NC=CN1 BNOUNCMFJUOMJQ-UHFFFAOYSA-N 0.000 description 2
- PVEFGWYDSWJBMN-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinylmethyl)-n-(2-methoxyethyl)-4-methylaniline Chemical compound COCCNC1=CC=C(C)C=C1CS(=O)C1=NC=CN1 PVEFGWYDSWJBMN-UHFFFAOYSA-N 0.000 description 2
- WJLPMICCAPTPSE-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinylmethyl)-n-(2-propan-2-yloxyethyl)aniline Chemical compound CC(C)OCCNC1=CC=CC=C1CS(=O)C1=NC=CN1 WJLPMICCAPTPSE-UHFFFAOYSA-N 0.000 description 2
- BXOJSBGOHDGMET-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinylmethyl)-n-(3-methoxypropyl)aniline Chemical compound COCCCNC1=CC=CC=C1CS(=O)C1=NC=CN1 BXOJSBGOHDGMET-UHFFFAOYSA-N 0.000 description 2
- XKVKVJDQIUCNMA-UHFFFAOYSA-N 2-[(2-ethoxyacetyl)amino]benzoic acid Chemical compound CCOCC(=O)NC1=CC=CC=C1C(O)=O XKVKVJDQIUCNMA-UHFFFAOYSA-N 0.000 description 2
- HVJVTUBMMSZNAA-UHFFFAOYSA-N 2-[(2-propan-2-yloxyacetyl)amino]benzoic acid Chemical compound CC(C)OCC(=O)NC1=CC=CC=C1C(O)=O HVJVTUBMMSZNAA-UHFFFAOYSA-N 0.000 description 2
- ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 2-ethoxyacetyl chloride Chemical compound CCOCC(Cl)=O ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 0.000 description 2
- RUTBVEQGLKVOOH-UHFFFAOYSA-N 2-methoxy-n-(4-methoxy-3,5-dimethylphenyl)acetamide Chemical compound COCC(=O)NC1=CC(C)=C(OC)C(C)=C1 RUTBVEQGLKVOOH-UHFFFAOYSA-N 0.000 description 2
- PHIQSJFVVPYMOR-UHFFFAOYSA-N 2-propan-2-yloxyacetyl chloride Chemical compound CC(C)OCC(Cl)=O PHIQSJFVVPYMOR-UHFFFAOYSA-N 0.000 description 2
- YDYGGTRULUZLFP-UHFFFAOYSA-N 4-methoxy-n-(2-methoxyethyl)-3,5-dimethylaniline Chemical compound COCCNC1=CC(C)=C(OC)C(C)=C1 YDYGGTRULUZLFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010908 decantation Methods 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- PUCRASXBZCKLBW-UHFFFAOYSA-N methyl 2-(3-methoxypropanoylamino)benzoate Chemical compound COCCC(=O)NC1=CC=CC=C1C(=O)OC PUCRASXBZCKLBW-UHFFFAOYSA-N 0.000 description 2
- ZQSAWKDSWWJRGP-UHFFFAOYSA-N methyl 2-[(2-methoxyacetyl)amino]benzoate Chemical compound COCC(=O)NC1=CC=CC=C1C(=O)OC ZQSAWKDSWWJRGP-UHFFFAOYSA-N 0.000 description 2
- MDHYFUPTSWXVIA-UHFFFAOYSA-N methyl 2-amino-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1N MDHYFUPTSWXVIA-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- YHGQTURVCLVYPN-UHFFFAOYSA-N n-(2-ethoxyethyl)-2-(1h-imidazol-2-ylsulfanylmethyl)-4-methylaniline Chemical compound CCOCCNC1=CC=C(C)C=C1CSC1=NC=CN1 YHGQTURVCLVYPN-UHFFFAOYSA-N 0.000 description 2
- RXXVAGGYYMVKBW-UHFFFAOYSA-N n-(2-ethoxyethyl)-2-(1h-imidazol-2-ylsulfanylmethyl)aniline Chemical compound CCOCCNC1=CC=CC=C1CSC1=NC=CN1 RXXVAGGYYMVKBW-UHFFFAOYSA-N 0.000 description 2
- NRSFWWPHANYJCQ-UHFFFAOYSA-N n-(2-ethoxyethyl)-2-(1h-imidazol-2-ylsulfinylmethyl)-4-methylaniline Chemical compound CCOCCNC1=CC=C(C)C=C1CS(=O)C1=NC=CN1 NRSFWWPHANYJCQ-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 239000012047 saturated solution Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- CJUIVMYXXYCWPD-UHFFFAOYSA-N 2-(1H-imidazol-2-ylsulfonylmethyl)-N-(2-methoxyethyl)aniline Chemical compound COCCNC1=C(CS(=O)(=O)C=2NC=CN=2)C=CC=C1 CJUIVMYXXYCWPD-UHFFFAOYSA-N 0.000 description 1
- NNWZWZHGQCQDLC-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanylmethyl)-n-(2-methoxyethyl)-3-methylaniline Chemical compound COCCNC1=CC=CC(C)=C1CSC1=NC=CN1 NNWZWZHGQCQDLC-UHFFFAOYSA-N 0.000 description 1
- KBUWRQKMJLUGPI-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfanylmethyl)-n-(3-methoxypropyl)aniline Chemical compound COCCCNC1=CC=CC=C1CSC1=NC=CN1 KBUWRQKMJLUGPI-UHFFFAOYSA-N 0.000 description 1
- KGTULBYEILHFRS-UHFFFAOYSA-N 2-[(2-ethoxyacetyl)amino]-5-methylbenzoic acid Chemical compound CCOCC(=O)NC1=CC=C(C)C=C1C(O)=O KGTULBYEILHFRS-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C33/00—Parts of bearings; Special methods for making bearings or parts thereof
- F16C33/72—Sealings
- F16C33/76—Sealings of ball or roller bearings
- F16C33/78—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members
- F16C33/7816—Details of the sealing or parts thereof, e.g. geometry, material
- F16C33/782—Details of the sealing or parts thereof, e.g. geometry, material of the sealing region
- F16C33/7823—Details of the sealing or parts thereof, e.g. geometry, material of the sealing region of sealing lips
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C33/00—Parts of bearings; Special methods for making bearings or parts thereof
- F16C33/72—Sealings
- F16C33/76—Sealings of ball or roller bearings
- F16C33/78—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members
- F16C33/784—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted to a groove in the inner surface of the outer race and extending toward the inner race
- F16C33/7843—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted to a groove in the inner surface of the outer race and extending toward the inner race with a single annular sealing disc
- F16C33/7853—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted to a groove in the inner surface of the outer race and extending toward the inner race with a single annular sealing disc with one or more sealing lips to contact the inner race
- F16C33/7856—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted to a groove in the inner surface of the outer race and extending toward the inner race with a single annular sealing disc with one or more sealing lips to contact the inner race with a single sealing lip
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C33/00—Parts of bearings; Special methods for making bearings or parts thereof
- F16C33/72—Sealings
- F16C33/76—Sealings of ball or roller bearings
- F16C33/78—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members
- F16C33/7869—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted with a cylindrical portion to the inner surface of the outer race and having a radial portion extending inward
- F16C33/7873—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted with a cylindrical portion to the inner surface of the outer race and having a radial portion extending inward with a single sealing ring of generally L-shaped cross-section
- F16C33/7876—Sealings of ball or roller bearings with a diaphragm, disc, or ring, with or without resilient members mounted with a cylindrical portion to the inner surface of the outer race and having a radial portion extending inward with a single sealing ring of generally L-shaped cross-section with sealing lips
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16J—PISTONS; CYLINDERS; SEALINGS
- F16J15/00—Sealings
- F16J15/16—Sealings between relatively-moving surfaces
- F16J15/32—Sealings between relatively-moving surfaces with elastic sealings, e.g. O-rings
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16J—PISTONS; CYLINDERS; SEALINGS
- F16J15/00—Sealings
- F16J15/16—Sealings between relatively-moving surfaces
- F16J15/32—Sealings between relatively-moving surfaces with elastic sealings, e.g. O-rings
- F16J15/3204—Sealings between relatively-moving surfaces with elastic sealings, e.g. O-rings with at least one lip
- F16J15/322—Sealings between relatively-moving surfaces with elastic sealings, e.g. O-rings with at least one lip supported in a direction perpendicular to the surfaces
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16J—PISTONS; CYLINDERS; SEALINGS
- F16J15/00—Sealings
- F16J15/16—Sealings between relatively-moving surfaces
- F16J15/32—Sealings between relatively-moving surfaces with elastic sealings, e.g. O-rings
- F16J15/3268—Mounting of sealing rings
- F16J15/3276—Mounting of sealing rings with additional static sealing between the sealing, or its casing or support, and the surface on which it is mounted
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C19/00—Bearings with rolling contact, for exclusively rotary movement
- F16C19/22—Bearings with rolling contact, for exclusively rotary movement with bearing rollers essentially of the same size in one or more circular rows, e.g. needle bearings
- F16C19/24—Bearings with rolling contact, for exclusively rotary movement with bearing rollers essentially of the same size in one or more circular rows, e.g. needle bearings for radial load mainly
- F16C19/26—Bearings with rolling contact, for exclusively rotary movement with bearing rollers essentially of the same size in one or more circular rows, e.g. needle bearings for radial load mainly with a single row of rollers
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C2361/00—Apparatus or articles in engineering in general
- F16C2361/61—Toothed gear systems, e.g. support of pinion shafts
Landscapes
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Epoxy Resins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Fats And Perfumes (AREA)
- Plural Heterocyclic Compounds (AREA)
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|---|---|---|---|
| JP20919289 | 1989-08-10 | ||
| JP209192 | 1989-08-10 |
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| RU2026293C1 true RU2026293C1 (ru) | 1995-01-09 |
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| SU904830916A RU2026293C1 (ru) | 1989-08-10 | 1990-09-09 | Способ получения производного имидазола |
| RU9393004729A RU2069212C1 (ru) | 1989-08-10 | 1993-03-29 | Производные имидазола |
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| RU9393004729A RU2069212C1 (ru) | 1989-08-10 | 1993-03-29 | Производные имидазола |
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| JP2614756B2 (ja) * | 1988-08-10 | 1997-05-28 | 日本ケミファ株式会社 | イミダゾール誘導体およびその製造法ならびにこれを含有する抗潰瘍剤 |
| JPH0770083A (ja) * | 1993-07-05 | 1995-03-14 | Nippon Chemiphar Co Ltd | イミダゾール誘導体を有効成分とする血圧降下剤 |
| JP3046924B2 (ja) * | 1995-03-27 | 2000-05-29 | 株式会社アラクス | イミダゾリン誘導体又はそれらの可能な互変異性体及びそれらの製造方法並びにそれらを有効成分とする創傷治療薬 |
| JP6086865B2 (ja) | 2011-08-03 | 2017-03-01 | 協和発酵キリン株式会社 | ジベンゾオキセピン誘導体 |
| CN108698982B (zh) * | 2016-01-14 | 2021-07-16 | 日产化学工业株式会社 | 含有氟原子的化合物及其利用 |
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| EP0251536A1 (en) * | 1986-06-24 | 1988-01-07 | FISONS plc | Benzimidazoles, their production, formulation and use as gastric acid secretion inhibitors |
| IT1222412B (it) * | 1987-07-31 | 1990-09-05 | Chiesi Farma Spa | Tiometil e sulfinil metil derivati ad azione antisecretiva acida gastrica,loro procedimento di preparazione e composizioni farmaceutiche che li contengono |
| JP2614756B2 (ja) * | 1988-08-10 | 1997-05-28 | 日本ケミファ株式会社 | イミダゾール誘導体およびその製造法ならびにこれを含有する抗潰瘍剤 |
-
1990
- 1990-08-08 AT AT90115236T patent/ATE102610T1/de not_active IP Right Cessation
- 1990-08-08 DK DK90115236.3T patent/DK0412529T3/da active
- 1990-08-08 DE DE69007203T patent/DE69007203T2/de not_active Expired - Fee Related
- 1990-08-08 EP EP90115236A patent/EP0412529B1/en not_active Expired - Lifetime
- 1990-08-08 ES ES90115236T patent/ES2062223T3/es not_active Expired - Lifetime
- 1990-08-08 ZA ZA906247A patent/ZA906247B/xx unknown
- 1990-08-08 CA CA002022903A patent/CA2022903A1/en not_active Abandoned
- 1990-08-09 NO NO903514A patent/NO179004C/no unknown
- 1990-08-09 HU HU904946A patent/HU206686B/hu not_active IP Right Cessation
- 1990-08-09 AU AU60851/90A patent/AU630839B2/en not_active Ceased
- 1990-08-10 KR KR1019900012311A patent/KR960011377B1/ko not_active Expired - Fee Related
- 1990-08-10 FI FI903967A patent/FI903967A7/fi not_active Application Discontinuation
- 1990-08-10 MX MX021942A patent/MX171158B/es unknown
- 1990-08-10 US US07/565,975 patent/US5091403A/en not_active Expired - Fee Related
- 1990-08-10 JP JP2213124A patent/JP2794640B2/ja not_active Expired - Lifetime
- 1990-08-10 PL PL90286432A patent/PL163654B1/pl unknown
- 1990-08-10 DD DD90343397A patent/DD297159A5/de not_active IP Right Cessation
- 1990-09-09 RU SU904830916A patent/RU2026293C1/ru active
-
1993
- 1993-03-29 RU RU9393004729A patent/RU2069212C1/ru active
Non-Patent Citations (1)
| Title |
|---|
| Вейганд-Хильгетаг, Методы эксперимента в органической химии, М.: Химия, 1968, с.592. * |
Also Published As
| Publication number | Publication date |
|---|---|
| HU904946D0 (en) | 1991-01-28 |
| DK0412529T3 (da) | 1994-04-05 |
| US5091403A (en) | 1992-02-25 |
| HU206686B (en) | 1992-12-28 |
| AU6085190A (en) | 1991-02-14 |
| ATE102610T1 (de) | 1994-03-15 |
| MX171158B (enExample) | 1993-10-05 |
| JP2794640B2 (ja) | 1998-09-10 |
| EP0412529A1 (en) | 1991-02-13 |
| NO179004B (no) | 1996-04-09 |
| FI903967A0 (fi) | 1990-08-10 |
| ES2062223T3 (es) | 1994-12-16 |
| RU2069212C1 (ru) | 1996-11-20 |
| NO179004C (no) | 1996-07-17 |
| NO903514L (no) | 1991-02-11 |
| FI903967A7 (fi) | 1991-02-11 |
| JPH03163065A (ja) | 1991-07-15 |
| CA2022903A1 (en) | 1991-02-11 |
| AU630839B2 (en) | 1992-11-05 |
| DE69007203D1 (de) | 1994-04-14 |
| NO903514D0 (no) | 1990-08-09 |
| EP0412529B1 (en) | 1994-03-09 |
| PL286432A1 (en) | 1991-04-22 |
| DE69007203T2 (de) | 1994-07-28 |
| KR910004573A (ko) | 1991-03-28 |
| KR960011377B1 (ko) | 1996-08-22 |
| PL163654B1 (pl) | 1994-04-29 |
| DD297159A5 (de) | 1992-01-02 |
| HUT54663A (en) | 1991-03-28 |
| ZA906247B (en) | 1991-06-26 |
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