NO841754L - Fremgangsmaate ved fremstilling av nye fluoralkoksyforbindelser - Google Patents
Fremgangsmaate ved fremstilling av nye fluoralkoksyforbindelserInfo
- Publication number
- NO841754L NO841754L NO841754A NO841754A NO841754L NO 841754 L NO841754 L NO 841754L NO 841754 A NO841754 A NO 841754A NO 841754 A NO841754 A NO 841754A NO 841754 L NO841754 L NO 841754L
- Authority
- NO
- Norway
- Prior art keywords
- methoxy
- residue
- hydrogen
- methyl
- pyridyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 114
- 238000000034 method Methods 0.000 title claims description 30
- JVTSHOJDBRTPHD-UHFFFAOYSA-N 2,2,2-trifluoroacetaldehyde Chemical compound FC(F)(F)C=O JVTSHOJDBRTPHD-UHFFFAOYSA-N 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 73
- 239000001257 hydrogen Substances 0.000 claims abstract description 73
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 38
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 23
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 19
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 13
- 239000011737 fluorine Substances 0.000 claims abstract description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical group 0.000 claims abstract description 9
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 6
- QPAXMPYBNSHKAK-UHFFFAOYSA-N chloro(difluoro)methane Chemical group F[C](F)Cl QPAXMPYBNSHKAK-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 alkyl radical Chemical class 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 17
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 16
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 16
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 16
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 16
- 239000007858 starting material Substances 0.000 claims description 15
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 9
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001556 benzimidazoles Chemical class 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- OMYYXOJVDCRZBD-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC=C(OC(F)(F)C(F)F)C=C3N=2)=C1C OMYYXOJVDCRZBD-UHFFFAOYSA-N 0.000 claims description 3
- CFILDZXKPBMVNO-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-6-(2,2,2-trifluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC=C(OCC(F)(F)F)C=C3N=2)=C1C CFILDZXKPBMVNO-UHFFFAOYSA-N 0.000 claims description 3
- IWECCZBOLCDNSE-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfinyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(OC(F)(F)C(F)F)=CC=C3N=2)=C1 IWECCZBOLCDNSE-UHFFFAOYSA-N 0.000 claims description 3
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 3
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical class C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 claims description 2
- RBGGMTQEVZWWLW-UHFFFAOYSA-N 1-methoxybenzimidazole Chemical compound C1=CC=C2N(OC)C=NC2=C1 RBGGMTQEVZWWLW-UHFFFAOYSA-N 0.000 claims description 2
- AQQUVYVCRJAMKM-UHFFFAOYSA-N 2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound COC1=C(C)C=NC(CS(=O)C=2NC3=CC=C(OC(F)(F)F)C=C3N=2)=C1C AQQUVYVCRJAMKM-UHFFFAOYSA-N 0.000 claims description 2
- JAJVJKRIHGUXJX-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(2,2,2-trifluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OCC(F)(F)F)C=C3N=2)=C1C JAJVJKRIHGUXJX-UHFFFAOYSA-N 0.000 claims description 2
- LDDGEZLWYOZBAQ-UHFFFAOYSA-N 2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CS(=O)C=2NC3=CC=C(OC(F)(F)F)C=C3N=2)=N1 LDDGEZLWYOZBAQ-UHFFFAOYSA-N 0.000 claims description 2
- YFDAYUXSRDTCHE-UHFFFAOYSA-N 2-[2-[[2-(1h-benzimidazol-2-yl)-1h-pyridin-2-yl]methylsulfanylmethyl]-1h-pyridin-2-yl]-1h-benzimidazole Chemical class N1C=CC=CC1(C=1NC2=CC=CC=C2N=1)CSCC1(C=2NC3=CC=CC=C3N=2)NC=CC=C1 YFDAYUXSRDTCHE-UHFFFAOYSA-N 0.000 claims description 2
- KNEMGJDWGUTNJX-UHFFFAOYSA-N 5,6-bis(difluoromethoxy)-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(OC(F)F)=C(OC(F)F)C=C3N=2)=C1C KNEMGJDWGUTNJX-UHFFFAOYSA-N 0.000 claims description 2
- KAUGJJICAPARHM-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(OC)=C(OC(F)F)C=C3N=2)=C1C KAUGJJICAPARHM-UHFFFAOYSA-N 0.000 claims description 2
- 150000004675 formic acid derivatives Chemical class 0.000 claims description 2
- 150000004987 o-phenylenediamines Chemical class 0.000 claims description 2
- 150000003222 pyridines Chemical class 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- QUNAPURTLGQPAG-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(C[S+]([O-])C=2NC3=CC=C(OC(F)(F)C(F)F)C=C3N=2)=C1C QUNAPURTLGQPAG-UHFFFAOYSA-N 0.000 claims 1
- WKIKQLQKPRSSCQ-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)(F)F)C=C3N=2)=C1 WKIKQLQKPRSSCQ-UHFFFAOYSA-N 0.000 claims 1
- 235000004431 Linum usitatissimum Nutrition 0.000 claims 1
- 240000006240 Linum usitatissimum Species 0.000 claims 1
- 235000004426 flaxseed Nutrition 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 abstract description 9
- 230000001681 protective effect Effects 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- 238000000354 decomposition reaction Methods 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 239000002904 solvent Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 235000011121 sodium hydroxide Nutrition 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000013543 active substance Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 229910017604 nitric acid Inorganic materials 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 235000015497 potassium bicarbonate Nutrition 0.000 description 5
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 5
- 239000011736 potassium bicarbonate Substances 0.000 description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 150000003568 thioethers Chemical class 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- FSKBGJJQSWUWKX-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC=C(OC(F)(F)F)C=C3N=2)=C1C FSKBGJJQSWUWKX-UHFFFAOYSA-N 0.000 description 3
- VTSXVHVTPWBBNM-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfanyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(OC(F)(F)C(F)F)=CC=C3N=2)=C1 VTSXVHVTPWBBNM-UHFFFAOYSA-N 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
- UIUCDMJOXYLFHF-UHFFFAOYSA-N 5-(1,1,2,2-tetrafluoroethoxy)-1,3-dihydrobenzimidazole-2-thione Chemical compound FC(F)C(F)(F)OC1=CC=C2NC(S)=NC2=C1 UIUCDMJOXYLFHF-UHFFFAOYSA-N 0.000 description 3
- 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 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 150000002902 organometallic compounds Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- YNQJHJPRQAPKHH-UHFFFAOYSA-N (4-methoxy-5-methylpyridin-2-yl)methanol Chemical compound COC1=CC(CO)=NC=C1C YNQJHJPRQAPKHH-UHFFFAOYSA-N 0.000 description 2
- ITQCXTOQWOFOGH-UHFFFAOYSA-N 1,2-bis(difluoromethoxy)benzene Chemical compound FC(F)OC1=CC=CC=C1OC(F)F ITQCXTOQWOFOGH-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- GFYHSKONPJXCDE-UHFFFAOYSA-N 2,3,5-trimethylpyridine Chemical compound CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 2
- FDNDPEVBJHZSAQ-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-5-methylpyridine;hydrochloride Chemical compound Cl.COC1=CC(CCl)=NC=C1C FDNDPEVBJHZSAQ-UHFFFAOYSA-N 0.000 description 2
- UODFFWGYSJVFCZ-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxypyridine Chemical compound COC1=CC=NC(CCl)=C1 UODFFWGYSJVFCZ-UHFFFAOYSA-N 0.000 description 2
- PBDFBZPTRXMFBL-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxypyridine;hydrochloride Chemical compound Cl.COC1=CC=NC(CCl)=C1 PBDFBZPTRXMFBL-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- NQYANFAPNZYLCA-UHFFFAOYSA-N 2-[(3-methylpyridin-2-yl)methylsulfanyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound CC1=CC=CN=C1CSC1=NC2=CC=C(OC(F)(F)C(F)F)C=C2N1 NQYANFAPNZYLCA-UHFFFAOYSA-N 0.000 description 2
- CJKBWPVBQKUARO-UHFFFAOYSA-N 2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfanyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound COC1=C(C)C=NC(CSC=2NC3=CC(OC(F)(F)C(F)F)=CC=C3N=2)=C1C CJKBWPVBQKUARO-UHFFFAOYSA-N 0.000 description 2
- FGGLBZJAVPSKQY-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)(F)F)C=C3N=2)=C1C FGGLBZJAVPSKQY-UHFFFAOYSA-N 0.000 description 2
- ULJDHENNWLMFBJ-UHFFFAOYSA-N 2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfanyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CSC=2NC3=CC=C(OC(F)(F)C(F)F)C=C3N=2)=N1 ULJDHENNWLMFBJ-UHFFFAOYSA-N 0.000 description 2
- MYVOKHHYLAQNCN-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfanyl]-6-(2,2,2-trifluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(OCC(F)(F)F)=CC=C3N=2)=C1 MYVOKHHYLAQNCN-UHFFFAOYSA-N 0.000 description 2
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 2
- VIWAEJFNSRESKR-UHFFFAOYSA-N 5-(2,2,2-trifluoroethoxy)-1,3-dihydrobenzimidazole-2-thione Chemical compound FC(F)(F)COC1=CC=C2NC(S)=NC2=C1 VIWAEJFNSRESKR-UHFFFAOYSA-N 0.000 description 2
- NUFWDNDRHPHQKU-UHFFFAOYSA-N 5-(difluoromethoxy)-6-fluoro-1,3-dihydrobenzimidazole-2-thione Chemical compound C1=C(F)C(OC(F)F)=CC2=C1NC(S)=N2 NUFWDNDRHPHQKU-UHFFFAOYSA-N 0.000 description 2
- ILGOKLXIKXKQTH-UHFFFAOYSA-N 5-(difluoromethoxy)-6-fluoro-2-[(4-methoxypyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(F)=C(OC(F)F)C=C3N=2)=C1 ILGOKLXIKXKQTH-UHFFFAOYSA-N 0.000 description 2
- LOXKKKCAYRCQMF-UHFFFAOYSA-N 5-(trifluoromethoxy)-1,3-dihydrobenzimidazole-2-thione Chemical compound FC(F)(F)OC1=CC=C2NC(S)=NC2=C1 LOXKKKCAYRCQMF-UHFFFAOYSA-N 0.000 description 2
- DSQPCNGMZUEKGX-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(OC(F)F)=CC=C3N=2)=C1C DSQPCNGMZUEKGX-UHFFFAOYSA-N 0.000 description 2
- QNRPYHKRKRITPM-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(4-methoxypyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC=C(OC(F)F)C=C3N=2)=C1 QNRPYHKRKRITPM-UHFFFAOYSA-N 0.000 description 2
- FEHQKCUTBSQOHG-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(OC)=C(OC(F)F)C=C3N=2)=C1C FEHQKCUTBSQOHG-UHFFFAOYSA-N 0.000 description 2
- PDDZMHNGOYVNGA-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxypyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(OC(F)F)=C(OC)C=C3N=2)=C1 PDDZMHNGOYVNGA-UHFFFAOYSA-N 0.000 description 2
- YBOXTUJLDCBPEO-UHFFFAOYSA-N 6-(trifluoromethoxy)-1h-benzimidazole Chemical compound FC(F)(F)OC1=CC=C2NC=NC2=C1 YBOXTUJLDCBPEO-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000005708 Sodium hypochlorite Substances 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 230000000026 anti-ulcerogenic effect Effects 0.000 description 2
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 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
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- ACDAPUOXXWLLSC-UHFFFAOYSA-N (3-methylpyridin-2-yl)methanol Chemical compound CC1=CC=CN=C1CO ACDAPUOXXWLLSC-UHFFFAOYSA-N 0.000 description 1
- PSEPRWKZZJWRCB-UHFFFAOYSA-N (4-methoxy-3,5-dimethylpyridin-2-yl)methanol Chemical compound COC1=C(C)C=NC(CO)=C1C PSEPRWKZZJWRCB-UHFFFAOYSA-N 0.000 description 1
- QDZLOVCSHPNYIF-UHFFFAOYSA-N (4-methoxy-3,5-dimethylpyridin-2-yl)methanol;hydrochloride Chemical compound Cl.COC1=C(C)C=NC(CO)=C1C QDZLOVCSHPNYIF-UHFFFAOYSA-N 0.000 description 1
- LSHQBGRAEVQZBJ-UHFFFAOYSA-N (4-methoxy-3-methylpyridin-2-yl)methanol Chemical compound COC1=CC=NC(CO)=C1C LSHQBGRAEVQZBJ-UHFFFAOYSA-N 0.000 description 1
- GBMRUSRMPOUVEK-UHFFFAOYSA-N (4-methoxypyridin-2-yl)methanol Chemical compound COC1=CC=NC(CO)=C1 GBMRUSRMPOUVEK-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- COLOHWPRNRVWPI-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound [CH2]C(F)(F)F COLOHWPRNRVWPI-UHFFFAOYSA-N 0.000 description 1
- GEPCOBGCHJWXKI-UHFFFAOYSA-N 1,2-bis(difluoromethoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OC(F)F)C(OC(F)F)=C1 GEPCOBGCHJWXKI-UHFFFAOYSA-N 0.000 description 1
- GJLRUCVWLFOGHP-UHFFFAOYSA-N 1-(difluoromethoxy)-2-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OC(F)F)C(F)=C1 GJLRUCVWLFOGHP-UHFFFAOYSA-N 0.000 description 1
- WNXSLMDVLZECHU-UHFFFAOYSA-N 1-(difluoromethoxy)-2-fluorobenzene Chemical compound FC(F)OC1=CC=CC=C1F WNXSLMDVLZECHU-UHFFFAOYSA-N 0.000 description 1
- QJVGEFIZRJQOSG-UHFFFAOYSA-N 1-(difluoromethoxy)-2-methoxybenzene Chemical compound COC1=CC=CC=C1OC(F)F QJVGEFIZRJQOSG-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
- VNSOCOWFQDIYTN-UHFFFAOYSA-N 1-nitro-4-(1,1,2,2-tetrafluoroethoxy)benzene Chemical compound [O-][N+](=O)C1=CC=C(OC(F)(F)C(F)F)C=C1 VNSOCOWFQDIYTN-UHFFFAOYSA-N 0.000 description 1
- PPYNEIXRXPMHLF-UHFFFAOYSA-N 1-nitro-4-(2,2,2-trifluoroethoxy)benzene Chemical compound [O-][N+](=O)C1=CC=C(OCC(F)(F)F)C=C1 PPYNEIXRXPMHLF-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
- YSBDSWBSEXCSSE-UHFFFAOYSA-N 2,3,5-trimethyl-1-oxidopyridin-1-ium Chemical compound CC1=CC(C)=C(C)[N+]([O-])=C1 YSBDSWBSEXCSSE-UHFFFAOYSA-N 0.000 description 1
- PKHPZNKXOBWFCX-UHFFFAOYSA-N 2-(4-hydroxy-3-phenylbenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C(C=2C=CC=CC=2)=C1 PKHPZNKXOBWFCX-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- DCKALIKGFDMDHB-UHFFFAOYSA-N 2-(chloromethyl)-3-methylpyridine;hydrochloride Chemical compound Cl.CC1=CC=CN=C1CCl DCKALIKGFDMDHB-UHFFFAOYSA-N 0.000 description 1
- LCJDHJOUOJSJGS-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridin-1-ium;chloride Chemical compound Cl.COC1=C(C)C=NC(CCl)=C1C LCJDHJOUOJSJGS-UHFFFAOYSA-N 0.000 description 1
- SRKVJDYNPSMHJM-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine Chemical compound COC1=C(C)C=NC(CCl)=C1C SRKVJDYNPSMHJM-UHFFFAOYSA-N 0.000 description 1
- UIRCDHHEYPUZGA-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-3-methylpyridine Chemical compound COC1=CC=NC(CCl)=C1C UIRCDHHEYPUZGA-UHFFFAOYSA-N 0.000 description 1
- WHAGSNVVBXOIGQ-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-3-methylpyridine;hydron;chloride Chemical compound Cl.COC1=CC=NC(CCl)=C1C WHAGSNVVBXOIGQ-UHFFFAOYSA-N 0.000 description 1
- OBXBULSBVVGPSM-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-5-methylpyridine Chemical compound COC1=CC(CCl)=NC=C1C OBXBULSBVVGPSM-UHFFFAOYSA-N 0.000 description 1
- UKSAGCUNNXEOBJ-UHFFFAOYSA-N 2-(difluoromethoxy)-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(OC(F)F)=C1 UKSAGCUNNXEOBJ-UHFFFAOYSA-N 0.000 description 1
- JIHPCRDGMVWPKO-UHFFFAOYSA-N 2-(difluoromethoxy)-1-methoxy-4-nitrobenzene Chemical compound COC1=CC=C([N+]([O-])=O)C=C1OC(F)F JIHPCRDGMVWPKO-UHFFFAOYSA-N 0.000 description 1
- PVNTURWWDZNXTK-UHFFFAOYSA-N 2-(difluoromethoxy)phenol Chemical compound OC1=CC=CC=C1OC(F)F PVNTURWWDZNXTK-UHFFFAOYSA-N 0.000 description 1
- JTRYBSJVQSMGLN-UHFFFAOYSA-N 2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound COC1=C(C)C=NC(CSC=2NC3=CC=C(OC(F)(F)F)C=C3N=2)=C1C JTRYBSJVQSMGLN-UHFFFAOYSA-N 0.000 description 1
- PAAVYWNJNQDEPO-UHFFFAOYSA-N 2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfanyl]-6-(2,2,2-trifluoroethoxy)-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CSC=2NC3=CC(OCC(F)(F)F)=CC=C3N=2)=N1 PAAVYWNJNQDEPO-UHFFFAOYSA-N 0.000 description 1
- PAMSITPYVOHDTA-UHFFFAOYSA-N 2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfinyl]-6-(2,2,2-trifluoroethoxy)-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CS(=O)C=2NC3=CC=C(OCC(F)(F)F)C=C3N=2)=N1 PAMSITPYVOHDTA-UHFFFAOYSA-N 0.000 description 1
- ACTHKVOAFDPCMB-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfinyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole;sodium Chemical compound [Na].COC1=CC=NC(CS(=O)C=2NC3=CC(OC(F)(F)C(F)F)=CC=C3N=2)=C1 ACTHKVOAFDPCMB-UHFFFAOYSA-N 0.000 description 1
- PLCLAAHXXUNFGG-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfinyl]-6-(2,2,2-trifluoroethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(OCC(F)(F)F)=CC=C3N=2)=C1 PLCLAAHXXUNFGG-UHFFFAOYSA-N 0.000 description 1
- WSSQBUCRTZMSNC-UHFFFAOYSA-N 2-[(4-methoxypyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole;sodium Chemical compound [Na].COC1=CC=NC(CS(=O)C=2NC3=CC(OC(F)(F)F)=CC=C3N=2)=C1 WSSQBUCRTZMSNC-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
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- SCUPFBBAAASCQI-UHFFFAOYSA-N 2-nitro-4-(1,1,2,2-tetrafluoroethoxy)aniline Chemical compound NC1=CC=C(OC(F)(F)C(F)F)C=C1[N+]([O-])=O SCUPFBBAAASCQI-UHFFFAOYSA-N 0.000 description 1
- IBGOUNGPWVVCMU-UHFFFAOYSA-N 2-nitro-4-(2,2,2-trifluoroethoxy)aniline Chemical compound NC1=CC=C(OCC(F)(F)F)C=C1[N+]([O-])=O IBGOUNGPWVVCMU-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
- BDYAFLAQGZKDEN-UHFFFAOYSA-N 3-(difluoromethoxy)-4-methoxybenzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.COC1=CC=C(N)C(N)=C1OC(F)F BDYAFLAQGZKDEN-UHFFFAOYSA-N 0.000 description 1
- FKPNDEAKCPPXFA-UHFFFAOYSA-N 4,5-bis(difluoromethoxy)benzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC(OC(F)F)=C(OC(F)F)C=C1N FKPNDEAKCPPXFA-UHFFFAOYSA-N 0.000 description 1
- ZQQSVTYLRGGCEI-UHFFFAOYSA-N 4-(1,1,2,2-tetrafluoroethoxy)aniline Chemical compound NC1=CC=C(OC(F)(F)C(F)F)C=C1 ZQQSVTYLRGGCEI-UHFFFAOYSA-N 0.000 description 1
- NTMLDDGMIGWWQR-UHFFFAOYSA-N 4-(1,1,2,2-tetrafluoroethoxy)benzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC=C(OC(F)(F)C(F)F)C=C1N NTMLDDGMIGWWQR-UHFFFAOYSA-N 0.000 description 1
- FGUCEIXGVYGHFQ-UHFFFAOYSA-N 4-(2,2,2-trifluoroethoxy)benzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC=C(OCC(F)(F)F)C=C1N FGUCEIXGVYGHFQ-UHFFFAOYSA-N 0.000 description 1
- FHRVMXFZUVYVPF-UHFFFAOYSA-N 4-(difluoromethoxy)-2-nitroaniline Chemical compound NC1=CC=C(OC(F)F)C=C1[N+]([O-])=O FHRVMXFZUVYVPF-UHFFFAOYSA-N 0.000 description 1
- SFKFBXGGZRBYSV-UHFFFAOYSA-N 4-(difluoromethoxy)-5-fluoro-2-nitroaniline Chemical compound NC1=CC(F)=C(OC(F)F)C=C1[N+]([O-])=O SFKFBXGGZRBYSV-UHFFFAOYSA-N 0.000 description 1
- VERWLIYXHGUJNC-UHFFFAOYSA-N 4-(difluoromethoxy)-5-fluorobenzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC(F)=C(OC(F)F)C=C1N VERWLIYXHGUJNC-UHFFFAOYSA-N 0.000 description 1
- KVNBQJQKOBMSCJ-UHFFFAOYSA-N 4-(difluoromethoxy)benzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC=C(OC(F)F)C=C1N KVNBQJQKOBMSCJ-UHFFFAOYSA-N 0.000 description 1
- XVDGHCYFJDVPMI-UHFFFAOYSA-N 4-(trifluoromethoxy)benzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC=C(OC(F)(F)F)C=C1N XVDGHCYFJDVPMI-UHFFFAOYSA-N 0.000 description 1
- QDTUQGSYECRXDO-UHFFFAOYSA-N 4-[chloro(difluoro)methoxy]aniline Chemical compound NC1=CC=C(OC(F)(F)Cl)C=C1 QDTUQGSYECRXDO-UHFFFAOYSA-N 0.000 description 1
- XIRWWVLLLFFCKR-UHFFFAOYSA-N 4-chloro-2-n-(difluoromethoxy)benzene-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NC1=CC=C(Cl)C=C1NOC(F)F XIRWWVLLLFFCKR-UHFFFAOYSA-N 0.000 description 1
- KBFYPWJIHBBGMI-UHFFFAOYSA-N 4-chloro-n-(difluoromethoxy)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1NOC(F)F KBFYPWJIHBBGMI-UHFFFAOYSA-N 0.000 description 1
- JOXZAMWCPXYFKC-UHFFFAOYSA-N 4-methoxy-2,3,5-trimethyl-1-oxidopyridin-1-ium Chemical compound COC1=C(C)C=[N+]([O-])C(C)=C1C JOXZAMWCPXYFKC-UHFFFAOYSA-N 0.000 description 1
- SJKMUJOONSBISV-UHFFFAOYSA-N 5,6-bis(difluoromethoxy)-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=C(C)C=NC(CS(=O)C=2NC3=CC(OC(F)F)=C(OC(F)F)C=C3N=2)=C1C SJKMUJOONSBISV-UHFFFAOYSA-N 0.000 description 1
- JYFIBMMGXOZEQQ-UHFFFAOYSA-N 5,6-bis(difluoromethoxy)-2-[(4-methoxypyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(OC(F)F)=C(OC(F)F)C=C3N=2)=C1 JYFIBMMGXOZEQQ-UHFFFAOYSA-N 0.000 description 1
- HJMVPNAZPFZXCP-UHFFFAOYSA-N 5-(difluoromethoxy)-1,3-dihydrobenzimidazole-2-thione Chemical compound FC(F)OC1=CC=C2NC(=S)NC2=C1 HJMVPNAZPFZXCP-UHFFFAOYSA-N 0.000 description 1
- MLCFZCMZGXEYFR-UHFFFAOYSA-N 5-(difluoromethoxy)-4-methoxy-2-nitroaniline Chemical compound COC1=CC([N+]([O-])=O)=C(N)C=C1OC(F)F MLCFZCMZGXEYFR-UHFFFAOYSA-N 0.000 description 1
- VKTGZKAOPIGEGV-UHFFFAOYSA-N 5-(difluoromethoxy)-6-fluoro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(C[S+]([O-])C=2NC3=CC(OC(F)F)=C(F)C=C3N=2)=C1C VKTGZKAOPIGEGV-UHFFFAOYSA-N 0.000 description 1
- MRMNXYTZDHFZAH-UHFFFAOYSA-N 5-(difluoromethoxy)-6-fluoro-2-[(4-methoxypyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(F)=C(OC(F)F)C=C3N=2)=C1 MRMNXYTZDHFZAH-UHFFFAOYSA-N 0.000 description 1
- CVGUWQXDJUTPJA-UHFFFAOYSA-N 5-(difluoromethoxy)-6-methoxy-1,3-dihydrobenzimidazole-2-thione Chemical compound C1=C(OC(F)F)C(OC)=CC2=C1N=C(S)N2 CVGUWQXDJUTPJA-UHFFFAOYSA-N 0.000 description 1
- PAZIMRITJLEBLC-UHFFFAOYSA-N 5-chloro-1-(difluoromethoxy)-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]benzimidazole Chemical compound COC1=CC=NC(CSC=2N(C3=CC=C(Cl)C=C3N=2)OC(F)F)=C1C PAZIMRITJLEBLC-UHFFFAOYSA-N 0.000 description 1
- HOJFZFCCABPOKS-UHFFFAOYSA-N 5-chloro-1-(difluoromethoxy)-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2N(C3=CC=C(Cl)C=C3N=2)OC(F)F)=C1C HOJFZFCCABPOKS-UHFFFAOYSA-N 0.000 description 1
- YOAUIFVQXRTFCL-UHFFFAOYSA-N 5-chloro-1-(difluoromethoxy)-2-[(4-methoxypyridin-2-yl)methylsulfanyl]benzimidazole Chemical compound COC1=CC=NC(CSC=2N(C3=CC=C(Cl)C=C3N=2)OC(F)F)=C1 YOAUIFVQXRTFCL-UHFFFAOYSA-N 0.000 description 1
- ADUMCUJHVIFJJL-UHFFFAOYSA-N 5-chloro-1-(difluoromethoxy)-2-[(4-methoxypyridin-2-yl)methylsulfinyl]benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2N(C3=CC=C(Cl)C=C3N=2)OC(F)F)=C1 ADUMCUJHVIFJJL-UHFFFAOYSA-N 0.000 description 1
- KSXFGUXVIGQRBE-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound N1C=2C=C(OC(F)(F)F)C(OC)=CC=2N=C1SCC1=NC=C(C)C(OC)=C1C KSXFGUXVIGQRBE-UHFFFAOYSA-N 0.000 description 1
- IHMQNKNQOXNOGD-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound N1C=2C=C(OC(F)(F)C(F)F)C(OC)=CC=2N=C1SCC1=NC=CC(OC)=C1C IHMQNKNQOXNOGD-UHFFFAOYSA-N 0.000 description 1
- IFLAWDXXSOCTDG-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(1,1,2,2-tetrafluoroethoxy)-1h-benzimidazole Chemical compound N1C=2C=C(OC(F)(F)C(F)F)C(OC)=CC=2N=C1S(=O)CC1=NC=CC(OC)=C1C IFLAWDXXSOCTDG-UHFFFAOYSA-N 0.000 description 1
- KTZROOXKWCNCEM-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound N1C=2C=C(OC(F)(F)F)C(OC)=CC=2N=C1S(=O)CC1=NC=CC(OC)=C1C KTZROOXKWCNCEM-UHFFFAOYSA-N 0.000 description 1
- FTHFFJKICFFRNQ-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CSC=2NC3=CC(OC(F)(F)F)=C(OC)C=C3N=2)=N1 FTHFFJKICFFRNQ-UHFFFAOYSA-N 0.000 description 1
- WGCMIINNXLIHQZ-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CS(=O)C=2NC3=CC(OC(F)(F)F)=C(OC)C=C3N=2)=N1 WGCMIINNXLIHQZ-UHFFFAOYSA-N 0.000 description 1
- WVZAERKKWYBFOA-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxypyridin-2-yl)methylsulfinyl]-6-(trifluoromethoxy)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(OC(F)(F)F)=C(OC)C=C3N=2)=C1 WVZAERKKWYBFOA-UHFFFAOYSA-N 0.000 description 1
- DINJNXVAXRKZEJ-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=C(C)C=NC(C[S+]([O-])C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1C DINJNXVAXRKZEJ-UHFFFAOYSA-N 0.000 description 1
- ASWLZURXLWNOQA-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(C[S+]([O-])C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1C ASWLZURXLWNOQA-UHFFFAOYSA-N 0.000 description 1
- NZUJDKFPDWCCKD-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfanyl]-1H-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CSC=2NC3=CC(OC(F)F)=CC=C3N=2)=N1 NZUJDKFPDWCCKD-UHFFFAOYSA-N 0.000 description 1
- KDLPLFBIOHDYKX-UHFFFAOYSA-N 6-(difluoromethoxy)-2-[(4-methoxypyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1 KDLPLFBIOHDYKX-UHFFFAOYSA-N 0.000 description 1
- LKKREGKNVROXKY-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound N1C=2C=C(OC(F)F)C(OC)=CC=2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C LKKREGKNVROXKY-UHFFFAOYSA-N 0.000 description 1
- JXZHEKDUYOGUIC-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CSC=2NC3=CC(OC)=C(OC(F)F)C=C3N=2)=N1 JXZHEKDUYOGUIC-UHFFFAOYSA-N 0.000 description 1
- OHKVXNNLTNQLTN-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxy-5-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound C1=C(C)C(OC)=CC(CS(=O)C=2NC3=CC(OC)=C(OC(F)F)C=C3N=2)=N1 OHKVXNNLTNQLTN-UHFFFAOYSA-N 0.000 description 1
- REGMDVMUFLYHIX-UHFFFAOYSA-N 6-(difluoromethoxy)-5-methoxy-2-[(4-methoxypyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(OC)=C(OC(F)F)C=C3N=2)=C1 REGMDVMUFLYHIX-UHFFFAOYSA-N 0.000 description 1
- KNACKZCPZFFLLS-UHFFFAOYSA-N 6-chloro-3-(difluoromethoxy)-1h-benzimidazole-2-thione Chemical compound C1=C(Cl)C=C2NC(=S)N(OC(F)F)C2=C1 KNACKZCPZFFLLS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- JCBIRTLFBDUSDL-UHFFFAOYSA-N Cl.ClCC1=NC=CC(=C1C)OC.S(=O)(Cl)Cl Chemical compound Cl.ClCC1=NC=CC(=C1C)OC.S(=O)(Cl)Cl JCBIRTLFBDUSDL-UHFFFAOYSA-N 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
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 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
- 229940123907 Disease modifying antirheumatic drug Drugs 0.000 description 1
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000009858 acid secretion Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 229950003153 amsonate Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960005242 camylofin Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000007799 cork Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- RBNPZEHAODHBPZ-UHFFFAOYSA-M dihydroxyaluminium Chemical compound O.O.NCC(=O)O[Al] RBNPZEHAODHBPZ-UHFFFAOYSA-M 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229950002281 fendizoate Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229950000177 hibenzate Drugs 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- GUCOPPBIPNYWRV-UHFFFAOYSA-N n-[2-nitro-4-(1,1,2,2-tetrafluoroethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OC(F)(F)C(F)F)C=C1[N+]([O-])=O GUCOPPBIPNYWRV-UHFFFAOYSA-N 0.000 description 1
- GLVCSHDYSVIDOR-UHFFFAOYSA-N n-[3,4-bis(difluoromethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OC(F)F)C(OC(F)F)=C1 GLVCSHDYSVIDOR-UHFFFAOYSA-N 0.000 description 1
- UFLSHCCECIDOQI-UHFFFAOYSA-N n-[3-(difluoromethoxy)-4-methoxyphenyl]acetamide Chemical compound COC1=CC=C(NC(C)=O)C=C1OC(F)F UFLSHCCECIDOQI-UHFFFAOYSA-N 0.000 description 1
- UIRBAARIPFMQLX-UHFFFAOYSA-N n-[4,5-bis(difluoromethoxy)-2-nitrophenyl]acetamide Chemical compound CC(=O)NC1=CC(OC(F)F)=C(OC(F)F)C=C1[N+]([O-])=O UIRBAARIPFMQLX-UHFFFAOYSA-N 0.000 description 1
- APPKNBWGBWXVQA-UHFFFAOYSA-N n-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OC(F)(F)C(F)F)C=C1 APPKNBWGBWXVQA-UHFFFAOYSA-N 0.000 description 1
- XWJZCTFTYLPSMG-UHFFFAOYSA-N n-[4-(2,2,2-trifluoroethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OCC(F)(F)F)C=C1 XWJZCTFTYLPSMG-UHFFFAOYSA-N 0.000 description 1
- YZAFOMJODXAJQD-UHFFFAOYSA-N n-[4-(difluoromethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OC(F)F)C=C1 YZAFOMJODXAJQD-UHFFFAOYSA-N 0.000 description 1
- RNAQYXPBRBVEBQ-UHFFFAOYSA-N n-[4-[chloro(difluoro)methoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(OC(F)(F)Cl)C=C1 RNAQYXPBRBVEBQ-UHFFFAOYSA-N 0.000 description 1
- UGJZRTBEADDGRO-UHFFFAOYSA-N n-[4-chloro-3-(difluoromethoxy)-2-nitrophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(Cl)C(OC(F)F)=C1[N+]([O-])=O UGJZRTBEADDGRO-UHFFFAOYSA-N 0.000 description 1
- BBULBKJDQUAZLY-UHFFFAOYSA-N n-[5-(difluoromethoxy)-4-methoxy-2-nitrophenyl]acetamide Chemical compound COC1=CC([N+]([O-])=O)=C(NC(C)=O)C=C1OC(F)F BBULBKJDQUAZLY-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 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
- 229940039748 oxalate Drugs 0.000 description 1
- 229960002369 oxyphencyclimine Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000005009 perfluoropropyl group Chemical group FC(C(C(F)(F)F)(F)F)(F)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-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
- 239000003586 protic polar solvent Substances 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical class OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000003134 recirculating effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- KEAYESYHFKHZAL-IGMARMGPSA-N sodium-23 atom Chemical compound [23Na] KEAYESYHFKHZAL-IGMARMGPSA-N 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 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
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000007306 turnover Effects 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
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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Investigating Or Analyzing Materials By The Use Of Ultrasonic Waves (AREA)
- Heat Treatment Of Sheet Steel (AREA)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH240183 | 1983-05-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
NO841754L true NO841754L (no) | 1984-11-05 |
Family
ID=4232920
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO841754A NO841754L (no) | 1983-05-03 | 1984-05-02 | Fremgangsmaate ved fremstilling av nye fluoralkoksyforbindelser |
Country Status (17)
Country | Link |
---|---|
US (1) | US4555518A (ja) |
EP (1) | EP0134400B1 (ja) |
JP (2) | JPS59206379A (ja) |
KR (1) | KR840009098A (ja) |
AT (1) | ATE87311T1 (ja) |
AU (1) | AU579316B2 (ja) |
DE (1) | DE3486109D1 (ja) |
DK (1) | DK217184A (ja) |
ES (2) | ES8604927A1 (ja) |
FI (1) | FI841759A (ja) |
GR (1) | GR79849B (ja) |
HU (1) | HU195220B (ja) |
IL (1) | IL71664A (ja) |
NO (1) | NO841754L (ja) |
NZ (1) | NZ208023A (ja) |
PT (1) | PT78518B (ja) |
ZA (1) | ZA843288B (ja) |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZW4585A1 (en) * | 1984-04-19 | 1985-11-20 | Hoffmann La Roche | Imidazole derivatives |
IL75400A (en) * | 1984-06-16 | 1988-10-31 | Byk Gulden Lomberg Chem Fab | Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same |
GB8417194D0 (en) * | 1984-07-05 | 1984-08-08 | Boots Co Plc | Therapeutic agents |
JPS6150978A (ja) * | 1984-08-16 | 1986-03-13 | Takeda Chem Ind Ltd | ピリジン誘導体およびその製造法 |
JPS6150979A (ja) * | 1984-08-16 | 1986-03-13 | Takeda Chem Ind Ltd | ピリジン誘導体およびその製造法 |
DE3430513A1 (de) * | 1984-08-18 | 1986-02-27 | Wella Ag, 6100 Darmstadt | Haarfaerbemittel mit diamino-tetrafluorethoxybenzolen sowie neue diamino-tetrafluorethoxybenzole |
IL76839A (en) * | 1984-10-31 | 1988-08-31 | Byk Gulden Lomberg Chem Fab | Picoline derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same |
US4738975A (en) * | 1985-07-02 | 1988-04-19 | Takeda Chemical Industries, Ltd. | Pyridine derivatives, and use as anti-ulcer agents |
JPS6261978A (ja) * | 1985-09-12 | 1987-03-18 | Otsuka Pharmaceut Co Ltd | 5−フルオロ−1h−ベンズイミダゾ−ル誘導体 |
DE3621215A1 (de) * | 1986-06-25 | 1988-01-07 | Bayer Ag | Fluorhaltige o-phenylendiamine und o-aminophenole |
JPH0643426B2 (ja) * | 1986-07-25 | 1994-06-08 | 東京田辺製薬株式会社 | イミダゾ〔4,5−b〕ピリジン誘導体、その製造法及びそれを含有する抗潰瘍剤 |
FI96860C (fi) * | 1987-06-17 | 1996-09-10 | Eisai Co Ltd | Analogiamenetelmä lääkeaineena käytettävän pyridiinijohdannaisen valmistamiseksi |
DK171989B1 (da) * | 1987-08-04 | 1997-09-08 | Takeda Chemical Industries Ltd | Fremgangsmåde til fremstilling af 2-(2-pyridylmethylsulfinyl)-benzimidazoler |
JPH03504497A (ja) * | 1988-05-25 | 1991-10-03 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | 新規フルオルアルコキシ化合物 |
US5223515A (en) * | 1988-08-18 | 1993-06-29 | Takeda Chemical Industries, Ltd. | Injectable solution containing a pyridyl methylsulfinylbenzimidazole |
AT391693B (de) * | 1988-11-15 | 1990-11-12 | Cl Pharma | Verfahren zur herstellung von 3-5-dimethyl-4methoxypyridinderivaten sowie neues zwischenprodukt hierfuer |
SE8804628D0 (sv) | 1988-12-22 | 1988-12-22 | Ab Haessle | New compounds |
EG19302A (en) * | 1988-12-22 | 1994-11-30 | Haessle Ab | Compound with gastric acid inhibitory effect and process for its preparation |
SE8804629D0 (sv) * | 1988-12-22 | 1988-12-22 | Ab Haessle | New therapeutically active compounds |
US4965269A (en) * | 1989-12-20 | 1990-10-23 | Ab Hassle | Therapeutically active chloro substituted benzimidazoles |
US5274099A (en) * | 1989-12-20 | 1993-12-28 | Aktiebolaget Hassle | Therapeutically active fluoro substituted benzimidazoles |
US5049674A (en) | 1989-12-20 | 1991-09-17 | Aktiebolaget Hassle | Therapeutically active fluoro substituted benzimidazoles |
WO1995015324A1 (de) | 1993-12-01 | 1995-06-08 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituierte aminoalkylaminopyridine |
DK1308159T3 (da) * | 1995-09-21 | 2005-02-14 | Pharma Pass Ii Llc | Farmaceutisk sammensætning indeholdende en syre-labil omeprazol og fremgangsmåde til fremstilling deraf |
US6262086B1 (en) | 1999-08-26 | 2001-07-17 | Robert R. Whittle | Pharmaceutical unit dosage form |
US6316020B1 (en) | 1999-08-26 | 2001-11-13 | Robert R. Whittle | Pharmaceutical formulations |
US6326384B1 (en) | 1999-08-26 | 2001-12-04 | Robert R. Whittle | Dry blend pharmaceutical unit dosage form |
US6312723B1 (en) | 1999-08-26 | 2001-11-06 | Robert R. Whittle | Pharmaceutical unit dosage form |
US6369087B1 (en) | 1999-08-26 | 2002-04-09 | Robert R. Whittle | Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same |
US6268385B1 (en) | 1999-08-26 | 2001-07-31 | Robert R. Whittle | Dry blend pharmaceutical formulations |
US6780880B1 (en) | 1999-08-26 | 2004-08-24 | Robert R. Whittle | FT-Raman spectroscopic measurement |
US6262085B1 (en) | 1999-08-26 | 2001-07-17 | Robert R. Whittle | Alkoxy substituted Benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same |
US6312712B1 (en) | 1999-08-26 | 2001-11-06 | Robert R. Whittle | Method of improving bioavailability |
ES2171116B1 (es) * | 2000-04-14 | 2003-08-01 | Esteve Quimica Sa | Procedimiento para la obtencion de derivados de (((piridil sustituido)metil)tio)bencimidazol. |
WO2002026210A2 (en) * | 2000-09-29 | 2002-04-04 | Geneva Pharmaceuticals Inc. | Proton pump inhibitor formulation |
US20030228363A1 (en) * | 2002-06-07 | 2003-12-11 | Patel Mahendra R. | Stabilized pharmaceutical compositons containing benzimidazole compounds |
CA2510849A1 (en) * | 2002-12-19 | 2004-07-08 | Teva Pharmaceutical Industries Ltd | Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates |
US7439367B2 (en) * | 2003-01-15 | 2008-10-21 | Cipla Limited | Pharmaceutical process and compounds prepared thereby |
EP1601667A2 (en) * | 2003-03-12 | 2005-12-07 | Teva Pharmaceutical Industries Limited | Crystalline and amorphous solids of pantoprazole and processes for their preparation |
EP1615913A2 (en) | 2003-06-10 | 2006-01-18 | Teva Pharmaceutical Industries Limited | Process for preparing 2-(pyridinyl)methyl sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
US20060024362A1 (en) | 2004-07-29 | 2006-02-02 | Pawan Seth | Composition comprising a benzimidazole and process for its manufacture |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4045564A (en) * | 1974-02-18 | 1977-08-30 | Ab Hassle | Benzimidazole derivatives useful as gastric acid secretion inhibitors |
SE416649B (sv) * | 1974-05-16 | 1981-01-26 | Haessle Ab | Forfarande for framstellning av foreningar som paverkar magsyrasekretionen |
LU77115A1 (ja) * | 1977-04-12 | 1979-01-18 | ||
LU77125A1 (ja) * | 1977-04-12 | 1979-01-18 | ||
SE7804231L (sv) * | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
FR2428035A1 (fr) * | 1978-06-05 | 1980-01-04 | Sankyo Co | Derives de benzothiazocine et de benzothiazonine, et leur application therapeutique |
CH642359A5 (en) * | 1978-10-02 | 1984-04-13 | Ciba Geigy Ag | Benzimidazole derivatives |
US4359465A (en) * | 1980-07-28 | 1982-11-16 | The Upjohn Company | Methods for treating gastrointestinal inflammation |
CH644116A5 (de) * | 1980-08-21 | 1984-07-13 | Hoffmann La Roche | Imidazolderivate. |
ZA825106B (en) * | 1981-08-13 | 1983-04-27 | Haessle Ab | Novel pharmaceutical compositions |
IE57646B1 (en) * | 1983-12-16 | 1993-02-10 | Wyeth John & Brother Ltd | Derivatives of imidazoquinolines and analogues thereof |
GB8526154D0 (en) * | 1985-02-06 | 1985-11-27 | Kotobuki Seiyaku Co Ltd | 2-substituted cyclo-heptoimidazoles |
KR950001015B1 (ko) * | 1986-01-10 | 1995-02-07 | 닛뽕 케미화 가부시끼가이샤 | 술폭시드 유도체의 제조방법 |
FR2597478B1 (fr) * | 1986-04-21 | 1988-12-16 | Esteve Labor Dr | Benzimidazoles et imidazopyridines sulfonamides, leur preparation et leur application en tant que medicaments. |
EP0251536A1 (en) * | 1986-06-24 | 1988-01-07 | FISONS plc | Benzimidazoles, their production, formulation and use as gastric acid secretion inhibitors |
JPH0643426B2 (ja) * | 1986-07-25 | 1994-06-08 | 東京田辺製薬株式会社 | イミダゾ〔4,5−b〕ピリジン誘導体、その製造法及びそれを含有する抗潰瘍剤 |
-
1984
- 1984-04-27 IL IL71664A patent/IL71664A/xx not_active IP Right Cessation
- 1984-04-27 HU HU864147A patent/HU195220B/hu unknown
- 1984-04-30 AU AU27500/84A patent/AU579316B2/en not_active Ceased
- 1984-05-01 US US06/606,872 patent/US4555518A/en not_active Expired - Fee Related
- 1984-05-01 DK DK217184A patent/DK217184A/da not_active Application Discontinuation
- 1984-05-02 NZ NZ208023A patent/NZ208023A/en unknown
- 1984-05-02 JP JP59087967A patent/JPS59206379A/ja active Granted
- 1984-05-02 GR GR74557A patent/GR79849B/el unknown
- 1984-05-02 NO NO841754A patent/NO841754L/no unknown
- 1984-05-02 PT PT78518A patent/PT78518B/pt unknown
- 1984-05-03 ES ES532149A patent/ES8604927A1/es not_active Expired
- 1984-05-03 AT AT84104993T patent/ATE87311T1/de not_active IP Right Cessation
- 1984-05-03 EP EP84104993A patent/EP0134400B1/de not_active Expired - Lifetime
- 1984-05-03 KR KR1019840002392A patent/KR840009098A/ko not_active Application Discontinuation
- 1984-05-03 ZA ZA843288A patent/ZA843288B/xx unknown
- 1984-05-03 DE DE8484104993T patent/DE3486109D1/de not_active Expired - Lifetime
- 1984-05-03 FI FI841759A patent/FI841759A/fi not_active Application Discontinuation
-
1985
- 1985-07-12 ES ES545145A patent/ES8603866A1/es not_active Expired
-
1992
- 1992-03-24 JP JP4065838A patent/JPH0586037A/ja active Granted
Also Published As
Publication number | Publication date |
---|---|
ES8603866A1 (es) | 1986-01-16 |
FI841759A (fi) | 1984-11-04 |
GR79849B (ja) | 1984-10-31 |
NZ208023A (en) | 1987-07-31 |
AU579316B2 (en) | 1988-11-24 |
KR840009098A (ko) | 1984-12-24 |
ES545145A0 (es) | 1986-01-16 |
ES8604927A1 (es) | 1986-03-01 |
EP0134400A3 (en) | 1985-12-11 |
ZA843288B (en) | 1984-12-24 |
ATE87311T1 (de) | 1993-04-15 |
JPH0586037A (ja) | 1993-04-06 |
DK217184D0 (da) | 1984-05-01 |
FI841759A0 (fi) | 1984-05-03 |
HU195220B (en) | 1988-04-28 |
IL71664A (en) | 1987-11-30 |
DK217184A (da) | 1984-11-04 |
EP0134400B1 (de) | 1993-03-24 |
ES532149A0 (es) | 1986-03-01 |
IL71664A0 (en) | 1984-07-31 |
DE3486109D1 (de) | 1993-04-29 |
JPH0572391B2 (ja) | 1993-10-12 |
AU2750084A (en) | 1984-11-08 |
PT78518A (de) | 1984-06-01 |
JPH0587508B2 (ja) | 1993-12-16 |
JPS59206379A (ja) | 1984-11-22 |
EP0134400A2 (de) | 1985-03-20 |
PT78518B (de) | 1986-07-14 |
US4555518A (en) | 1985-11-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO841754L (no) | Fremgangsmaate ved fremstilling av nye fluoralkoksyforbindelser | |
US4758579A (en) | Fluoroalkoxy substituted benzimidazoles useful as gastric acid secretion inhibitors | |
US4686230A (en) | Picoline derivative useful as gastric acid secretion inhibitors | |
US4472409A (en) | 2-Pyridylmethyl thio(sulfinyl)benzimidazoles with gastric acid secretion inhibiting effects | |
AU2006274037B2 (en) | Isotopically substituted pantoprazole | |
US4560693A (en) | [1,3]-Dioxolo[4,5-f]benzimidazoles and [1,4]-dioxino[2,3-f]benzimidazoles | |
NO311618B1 (no) | Substituerte aralkyltioalkyltiopyridin til bekjempelse av Helicobacter-bakterier | |
JPS6122079A (ja) | ジアルコキシピリジン及びそれを含有する薬剤 | |
AU2006274036B2 (en) | Isotopically substituted proton pump inhibitors | |
JPH05117268A (ja) | ピリジン化合物 | |
DE3415971A1 (de) | Acylierte benzimidazole, verfahren zu ihrer herstellung, ihre anwendung und sie enthaltende arzneimittel | |
JPH03504497A (ja) | 新規フルオルアルコキシ化合物 | |
US7601737B2 (en) | Isotopically substituted proton pump inhibitors | |
KR20000016484A (ko) | 신규 화합물 |