DE60304726T2 - Benzimidazolderivative und ihre verwendung als prodrugs für protonenpumpenhemmer - Google Patents

Info

Publication number

DE60304726T2

DE60304726T2 DE60304726T DE60304726T DE60304726T2 DE 60304726 T2 DE60304726 T2 DE 60304726T2 DE 60304726 T DE60304726 T DE 60304726T DE 60304726 T DE60304726 T DE 60304726T DE 60304726 T2 DE60304726 T2 DE 60304726T2

Authority

DE

Germany

Prior art keywords

sulfonyl

mixture

methoxy

compound

formula

Prior art date

2002-07-19

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

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• 239000000651 prodrug Substances 0.000 title abstract description 38
• 229940002612 prodrug Drugs 0.000 title abstract description 38
• 239000003112 inhibitor Substances 0.000 title description 5
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 2
• 150000001556 benzimidazoles Chemical class 0.000 title 1
• 150000003839 salts Chemical class 0.000 claims abstract description 27
• 150000001875 compounds Chemical class 0.000 claims description 240
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 20
• 150000003536 tetrazoles Chemical group 0.000 claims description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 claims description 3
• 108010083204 Proton Pumps Proteins 0.000 claims description 3
• 125000005843 halogen group Chemical group 0.000 claims description 3
• 229930195734 saturated hydrocarbon Natural products 0.000 claims description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 11
• 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
• 239000003795 chemical substances by application Substances 0.000 claims 1
• 229940126409 proton pump inhibitor Drugs 0.000 abstract description 42
• 239000000612 proton pump inhibitor Substances 0.000 abstract description 42
• 230000002378 acidificating effect Effects 0.000 abstract description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 411
• 239000000543 intermediate Substances 0.000 description 342
• 239000000203 mixture Substances 0.000 description 326
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 190
• 239000007787 solid Substances 0.000 description 187
• 239000000243 solution Substances 0.000 description 165
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 157
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 153
• 235000019439 ethyl acetate Nutrition 0.000 description 147
• -1 Mono- Chemical class 0.000 description 142
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 136
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 105
• 238000006243 chemical reaction Methods 0.000 description 95
• 238000005160 1H NMR spectroscopy Methods 0.000 description 91
• 230000002829 reductive effect Effects 0.000 description 88
• 239000011541 reaction mixture Substances 0.000 description 74
• 239000006260 foam Substances 0.000 description 68
• 239000012044 organic layer Substances 0.000 description 61
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
• 239000003814 drug Substances 0.000 description 51
• 239000010410 layer Substances 0.000 description 51
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 46
• 229940079593 drug Drugs 0.000 description 46
• 239000000741 silica gel Substances 0.000 description 44
• 229910002027 silica gel Inorganic materials 0.000 description 44
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
• 239000000706 filtrate Substances 0.000 description 40
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 37
• 239000002253 acid Substances 0.000 description 34
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 33
• 238000004440 column chromatography Methods 0.000 description 33
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
• 238000001704 evaporation Methods 0.000 description 30
• 230000008020 evaporation Effects 0.000 description 30
• 238000001914 filtration Methods 0.000 description 30
• 239000002244 precipitate Substances 0.000 description 30
• MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 29
• SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 28
• 238000010992 reflux Methods 0.000 description 25
• 238000003756 stirring Methods 0.000 description 25
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• 239000012267 brine Substances 0.000 description 23
• 239000000463 material Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 239000002904 solvent Substances 0.000 description 23
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• 239000000047 product Substances 0.000 description 22
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 159000000000 sodium salts Chemical class 0.000 description 21
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
• 238000003818 flash chromatography Methods 0.000 description 19
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
• 229960003174 lansoprazole Drugs 0.000 description 18
• 230000005764 inhibitory process Effects 0.000 description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
• 229960000381 omeprazole Drugs 0.000 description 17
• SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 16
• 239000008241 heterogeneous mixture Substances 0.000 description 16
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 15
• 235000017557 sodium bicarbonate Nutrition 0.000 description 15
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• 238000005481 NMR spectroscopy Methods 0.000 description 14
• 230000027119 gastric acid secretion Effects 0.000 description 14
• 238000000034 method Methods 0.000 description 14
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
• 238000011282 treatment Methods 0.000 description 14
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 13
• QJFIXBNLKARINT-UHFFFAOYSA-N 2-(4-methylphenyl)sulfonylethanol Chemical compound CC1=CC=C(S(=O)(=O)CCO)C=C1 QJFIXBNLKARINT-UHFFFAOYSA-N 0.000 description 13
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 13
• 125000001424 substituent group Chemical group 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 12
• 230000007062 hydrolysis Effects 0.000 description 12
• 238000006460 hydrolysis reaction Methods 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 12
• 239000003039 volatile agent Substances 0.000 description 12
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 11
• 0 C*c1c(*)ccc(C(O)=O)c1 Chemical compound C*c1c(*)ccc(C(O)=O)c1 0.000 description 11
• ABDMQSFNJPYOLA-UHFFFAOYSA-N NS(=O)(=O)[N+]([O-])=O Chemical compound NS(=O)(=O)[N+]([O-])=O ABDMQSFNJPYOLA-UHFFFAOYSA-N 0.000 description 11
• 239000002198 insoluble material Substances 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 150000003462 sulfoxides Chemical class 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• 230000009858 acid secretion Effects 0.000 description 10
• RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 10
• 201000010099 disease Diseases 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 230000002496 gastric effect Effects 0.000 description 10
• 238000002560 therapeutic procedure Methods 0.000 description 10
• 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 9
• SZWUWOIXOITMLC-UHFFFAOYSA-N 2-[4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]butanoic acid Chemical compound C1=CC(OC(CC)C(O)=O)=CC=C1S(=O)(=O)N1C2=CC=CC=C2N=C1S(=O)CC1=NC=CC(OCC(F)(F)F)=C1C SZWUWOIXOITMLC-UHFFFAOYSA-N 0.000 description 9
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 9
• 229910052786 argon Inorganic materials 0.000 description 9
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 9
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• VHTOWLOOYYGTNQ-UHFFFAOYSA-M sodium;2-[4-[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]acetate Chemical compound [Na+].N=1C2=CC(OC)=CC=C2N(S(=O)(=O)C=2C=CC(OCC([O-])=O)=CC=2)C=1S(=O)CC1=NC=C(C)C(OC)=C1C VHTOWLOOYYGTNQ-UHFFFAOYSA-M 0.000 description 8
• YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical class C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 7
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 7
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 235000008504 concentrate Nutrition 0.000 description 7
• 239000012141 concentrate Substances 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 238000001035 drying Methods 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 125000004494 ethyl ester group Chemical group 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 7
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 description 7
• 229960004157 rabeprazole Drugs 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 7
• UDWXLZLRRVQONG-UHFFFAOYSA-M sodium hexanoate Chemical compound [Na+].CCCCCC([O-])=O UDWXLZLRRVQONG-UHFFFAOYSA-M 0.000 description 7
• 229940001584 sodium metabisulfite Drugs 0.000 description 7
• 235000010262 sodium metabisulphite Nutrition 0.000 description 7
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 6
• 239000007868 Raney catalyst Substances 0.000 description 6
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
• 229910000564 Raney nickel Inorganic materials 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 229940125904 compound 1 Drugs 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 239000012258 stirred mixture Substances 0.000 description 6
• 238000004809 thin layer chromatography Methods 0.000 description 6
• VMORQDKKMBAQPJ-UHFFFAOYSA-N 2-(3-nitrophenyl)sulfonylethanol Chemical compound OCCS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 VMORQDKKMBAQPJ-UHFFFAOYSA-N 0.000 description 5
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
• QFMJFXFXQAFGBO-UHFFFAOYSA-N 4-methoxy-2-nitroaniline Chemical compound COC1=CC=C(N)C([N+]([O-])=O)=C1 QFMJFXFXQAFGBO-UHFFFAOYSA-N 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000006227 byproduct Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 201000006549 dyspepsia Diseases 0.000 description 5
• 239000012530 fluid Substances 0.000 description 5
• 239000003365 glass fiber Substances 0.000 description 5
• 150000002500 ions Chemical class 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 229960005019 pantoprazole Drugs 0.000 description 5
• 238000005055 short column chromatography Methods 0.000 description 5
• 210000002784 stomach Anatomy 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 4
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 4
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 4
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 4
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• IFLUFCAERNALRL-UHFFFAOYSA-N methyl 2-(4-chlorosulfonyl-3,5-dimethylphenoxy)acetate Chemical compound COC(=O)COC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 IFLUFCAERNALRL-UHFFFAOYSA-N 0.000 description 2
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• LALHSXSTFTTYOU-UHFFFAOYSA-N methyl 2-[4-[(4-methoxy-2-nitrophenyl)sulfamoyl]-3,5-dimethylphenoxy]acetate Chemical compound CC1=CC(OCC(=O)OC)=CC(C)=C1S(=O)(=O)NC1=CC=C(OC)C=C1[N+]([O-])=O LALHSXSTFTTYOU-UHFFFAOYSA-N 0.000 description 2
• PLIMJQDBOVDLDC-UHFFFAOYSA-N methyl 2-[4-[(5-methoxy-2-nitrophenyl)sulfamoyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1S(=O)(=O)NC1=CC(OC)=CC=C1[N+]([O-])=O PLIMJQDBOVDLDC-UHFFFAOYSA-N 0.000 description 2
• GHCBDAGOSQDZEM-UHFFFAOYSA-N methyl 2-[4-[(5-methoxy-2-sulfanylidene-1,3-dihydrobenzimidazol-4-yl)sulfonyl]-3,5-dimethylphenoxy]acetate Chemical compound CC1=CC(OCC(=O)OC)=CC(C)=C1S(=O)(=O)C1=C(OC)C=CC2=C1NC(=S)N2 GHCBDAGOSQDZEM-UHFFFAOYSA-N 0.000 description 2
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• BUUJFBCWPJMSKY-UHFFFAOYSA-N methyl 2-[4-[[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfonyl]-1h-benzimidazol-4-yl]sulfonyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1S(=O)(=O)C1=C(OC)C=CC2=C1N=C(S(=O)(=O)CC=1C(=C(OC)C(C)=CN=1)C)N2 BUUJFBCWPJMSKY-UHFFFAOYSA-N 0.000 description 2
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• KJRFTNVYOAGTHK-UHFFFAOYSA-N methyl 3-hydroxy-2,2-dimethylpropanoate Chemical compound COC(=O)C(C)(C)CO KJRFTNVYOAGTHK-UHFFFAOYSA-N 0.000 description 2
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
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• KMPLDGYSZGKRPI-UHFFFAOYSA-N n-(2-amino-4-methoxyphenyl)sulfamoyl chloride Chemical class COC1=CC=C(NS(Cl)(=O)=O)C(N)=C1 KMPLDGYSZGKRPI-UHFFFAOYSA-N 0.000 description 2
• XVLURDUTTWZFTP-UHFFFAOYSA-N n-(3-methoxyphenyl)sulfamoyl chloride Chemical class COC1=CC=CC(NS(Cl)(=O)=O)=C1 XVLURDUTTWZFTP-UHFFFAOYSA-N 0.000 description 2
• ISRXMEYARGEVIU-UHFFFAOYSA-N n-methyl-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C)C(C)C ISRXMEYARGEVIU-UHFFFAOYSA-N 0.000 description 2
• 229910017604 nitric acid Inorganic materials 0.000 description 2
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• LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 2
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• ODRFWMPKXHZIMQ-UHFFFAOYSA-M sodium;2,2-dimethyl-3-[4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]propanoate Chemical compound [Na+].CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(OCC(C)(C)C([O-])=O)C=C1 ODRFWMPKXHZIMQ-UHFFFAOYSA-M 0.000 description 2
• LDJUQGPKELJRQW-UHFFFAOYSA-M sodium;2-[3-methyl-4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonyl-5-propan-2-ylphenoxy]acetate Chemical compound [Na+].CC(C)C1=CC(OCC([O-])=O)=CC(C)=C1S(=O)(=O)N1C2=CC=CC=C2N=C1S(=O)CC1=NC=CC(OCC(F)(F)F)=C1C LDJUQGPKELJRQW-UHFFFAOYSA-M 0.000 description 2
• XWQAQCGEPXBGGU-UHFFFAOYSA-M sodium;2-[4-[6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]acetate Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2N(C3=CC(OC(F)F)=CC=C3N=2)S(=O)(=O)C=2C=CC(OCC([O-])=O)=CC=2)=C1OC XWQAQCGEPXBGGU-UHFFFAOYSA-M 0.000 description 2
• NUWPMCDSMVPZPF-UHFFFAOYSA-M sodium;2-[4-[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonyl-3,5-dimethylphenoxy]acetate Chemical compound [Na+].C12=CC(OC)=CC=C2N=C(S(=O)CC=2C(=C(OC)C(C)=CN=2)C)N1S(=O)(=O)C1=C(C)C=C(OCC([O-])=O)C=C1C NUWPMCDSMVPZPF-UHFFFAOYSA-M 0.000 description 2
• OBFLIVOVAAJYAH-UHFFFAOYSA-M sodium;2-methoxy-5-[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].N=1C2=CC(OC)=CC=C2N(S(=O)(=O)C=2C=C(C(OC)=CC=2)C([O-])=O)C=1S(=O)CC1=NC=C(C)C(OC)=C1C OBFLIVOVAAJYAH-UHFFFAOYSA-M 0.000 description 2
• AOZONSBBJWNYIX-UHFFFAOYSA-M sodium;2-methoxy-5-[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].C12=CC(OC)=CC=C2N=C(S(=O)CC=2C(=C(OC)C(C)=CN=2)C)N1S(=O)(=O)C1=CC=C(OC)C(C([O-])=O)=C1 AOZONSBBJWNYIX-UHFFFAOYSA-M 0.000 description 2
• VXGYRNPVOTZHEB-UHFFFAOYSA-M sodium;3-[2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonyl-4-methylbenzoate Chemical compound [Na+].COCCCOC1=CC=NC(CS(=O)C=2N(C3=CC=CC=C3N=2)S(=O)(=O)C=2C(=CC=C(C=2)C([O-])=O)C)=C1C VXGYRNPVOTZHEB-UHFFFAOYSA-M 0.000 description 2
• RMDQVXDVNBCQHM-UHFFFAOYSA-M sodium;3-[2-methoxy-5-[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylphenyl]propanoate Chemical compound [Na+].C12=CC(OC)=CC=C2N=C(S(=O)CC=2C(=C(OC)C(C)=CN=2)C)N1S(=O)(=O)C1=CC=C(OC)C(CCC([O-])=O)=C1 RMDQVXDVNBCQHM-UHFFFAOYSA-M 0.000 description 2
• CZYNETWEJOTPOO-UHFFFAOYSA-M sodium;3-[5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonyl-4-methylbenzoate Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2N(C3=CC=C(OC(F)F)C=C3N=2)S(=O)(=O)C=2C(=CC=C(C=2)C([O-])=O)C)=C1OC CZYNETWEJOTPOO-UHFFFAOYSA-M 0.000 description 2
• USFCAERJJFOWPX-UHFFFAOYSA-M sodium;3-[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonyl-4-methylbenzoate Chemical compound [Na+].N=1C2=CC(OC)=CC=C2N(S(=O)(=O)C=2C(=CC=C(C=2)C([O-])=O)C)C=1S(=O)CC1=NC=C(C)C(OC)=C1C USFCAERJJFOWPX-UHFFFAOYSA-M 0.000 description 2
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• YYXOABYKCBGIKP-UHFFFAOYSA-N 2-(3-nitrophenyl)sulfonylethyl 4-[[2-(3-propan-2-ylphenoxy)acetyl]amino]butanoate Chemical compound CC(C)c1cccc(OCC(=O)NCCCC(=O)OCCS(=O)(=O)c2cccc(c2)[N+]([O-])=O)c1 YYXOABYKCBGIKP-UHFFFAOYSA-N 0.000 description 1
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• GLHFJVODIOTKHO-UHFFFAOYSA-N 2-(3-nitrophenyl)sulfonylethyl 6-[[2-(3,5-dimethylphenoxy)acetyl]amino]hexanoate Chemical compound CC1=CC(C)=CC(OCC(=O)NCCCCCC(=O)OCCS(=O)(=O)C=2C=C(C=CC=2)[N+]([O-])=O)=C1 GLHFJVODIOTKHO-UHFFFAOYSA-N 0.000 description 1
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• ZWCHJLLQLTVZFX-UHFFFAOYSA-M sodium;2-[4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]butanoate Chemical compound [Na+].C1=CC(OC(CC)C([O-])=O)=CC=C1S(=O)(=O)N1C2=CC=CC=C2N=C1S(=O)CC1=NC=CC(OCC(F)(F)F)=C1C ZWCHJLLQLTVZFX-UHFFFAOYSA-M 0.000 description 1
• ZPPCPUZUJFWJBD-UHFFFAOYSA-M sodium;2-[4-[2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonyl-3,5-dimethylphenoxy]acetate Chemical compound [Na+].COCCCOC1=CC=NC(CS(=O)C=2N(C3=CC=CC=C3N=2)S(=O)(=O)C=2C(=CC(OCC([O-])=O)=CC=2C)C)=C1C ZPPCPUZUJFWJBD-UHFFFAOYSA-M 0.000 description 1
• KRGPEWCUYMCJSR-UHFFFAOYSA-M sodium;2-[4-[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonyl-3,5-dimethylphenoxy]acetate Chemical compound [Na+].N=1C2=CC(OC)=CC=C2N(S(=O)(=O)C=2C(=CC(OCC([O-])=O)=CC=2C)C)C=1S(=O)CC1=NC=C(C)C(OC)=C1C KRGPEWCUYMCJSR-UHFFFAOYSA-M 0.000 description 1
• JYALOXAUXSEFPE-UHFFFAOYSA-M sodium;2-[4-[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]acetate Chemical compound [Na+].C12=CC(OC)=CC=C2N=C(S(=O)CC=2C(=C(OC)C(C)=CN=2)C)N1S(=O)(=O)C1=CC=C(OCC([O-])=O)C=C1 JYALOXAUXSEFPE-UHFFFAOYSA-M 0.000 description 1
• XSQDSLULPAFCHM-UHFFFAOYSA-M sodium;2-[4-[[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazol-4-yl]sulfonyl]phenoxy]acetate Chemical compound [Na+].N1C2=CC(OC)=CC(S(=O)(=O)C=3C=CC(OCC([O-])=O)=CC=3)=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C XSQDSLULPAFCHM-UHFFFAOYSA-M 0.000 description 1
• FPMFWHCMRZZBEO-UHFFFAOYSA-M sodium;3-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1S(=O)(=O)C1=CC=CC(C([O-])=O)=C1 FPMFWHCMRZZBEO-UHFFFAOYSA-M 0.000 description 1
• VXOLALKAQMHQRM-UHFFFAOYSA-M sodium;3-[2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].COCCCOC1=CC=NC(CS(=O)C=2N(C3=CC=CC=C3N=2)S(=O)(=O)C=2C=C(C=CC=2)C([O-])=O)=C1C VXOLALKAQMHQRM-UHFFFAOYSA-M 0.000 description 1
• LZZZIVSJVQPROX-UHFFFAOYSA-M sodium;3-[2-methoxy-5-[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylphenyl]propanoate Chemical compound [Na+].N=1C2=CC(OC)=CC=C2N(S(=O)(=O)C=2C=C(CCC([O-])=O)C(OC)=CC=2)C=1S(=O)CC1=NC=C(C)C(OC)=C1C LZZZIVSJVQPROX-UHFFFAOYSA-M 0.000 description 1
• KCBPAWCMYCIOSW-UHFFFAOYSA-M sodium;3-[4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylphenyl]propanoate Chemical compound [Na+].CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(CCC([O-])=O)C=C1 KCBPAWCMYCIOSW-UHFFFAOYSA-M 0.000 description 1
• VOTQAEFEGJDKJQ-UHFFFAOYSA-M sodium;3-[4-[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]-2,2-dimethylpropanoate Chemical compound [Na+].N=1C2=CC(OC)=CC=C2N(S(=O)(=O)C=2C=CC(OCC(C)(C)C([O-])=O)=CC=2)C=1S(=O)CC1=NC=C(C)C(OC)=C1C VOTQAEFEGJDKJQ-UHFFFAOYSA-M 0.000 description 1
• MSEIMBLLYWPPMI-UHFFFAOYSA-M sodium;3-[4-[[5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazol-4-yl]sulfonyl]phenyl]propanoate Chemical compound [Na+].COC1=CC=C2NC(S(=O)CC=3C(=C(OC)C(C)=CN=3)C)=NC2=C1S(=O)(=O)C1=CC=C(CCC([O-])=O)C=C1 MSEIMBLLYWPPMI-UHFFFAOYSA-M 0.000 description 1
• CKINPSZRTCUTCU-UHFFFAOYSA-M sodium;3-[5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2N(C3=CC=C(OC(F)F)C=C3N=2)S(=O)(=O)C=2C=C(C=CC=2)C([O-])=O)=C1OC CKINPSZRTCUTCU-UHFFFAOYSA-M 0.000 description 1
• BUICRWKAKFVAFQ-UHFFFAOYSA-M sodium;3-[6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonyl-4-methylbenzoate Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2N(C3=CC(OC(F)F)=CC=C3N=2)S(=O)(=O)C=2C(=CC=C(C=2)C([O-])=O)C)=C1OC BUICRWKAKFVAFQ-UHFFFAOYSA-M 0.000 description 1
• YAFZZWHJSXSTBH-UHFFFAOYSA-M sodium;3-[6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2N(C3=CC(OC(F)F)=CC=C3N=2)S(=O)(=O)C=2C=C(C=CC=2)C([O-])=O)=C1OC YAFZZWHJSXSTBH-UHFFFAOYSA-M 0.000 description 1
• NYHHVYYPOOYHKI-UHFFFAOYSA-M sodium;3-[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].C12=CC(OC)=CC=C2N=C(S(=O)CC=2C(=C(OC)C(C)=CN=2)C)N1S(=O)(=O)C1=CC=CC(C([O-])=O)=C1 NYHHVYYPOOYHKI-UHFFFAOYSA-M 0.000 description 1
• OTPOXMBFEVYMTN-UHFFFAOYSA-M sodium;4-[[2-[4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonyl-3-propan-2-ylphenoxy]acetyl]amino]butanoate Chemical compound [Na+].CC(C)C1=CC(OCC(=O)NCCCC([O-])=O)=CC=C1S(=O)(=O)N1C2=CC=CC=C2N=C1S(=O)CC1=NC=CC(OCC(F)(F)F)=C1C OTPOXMBFEVYMTN-UHFFFAOYSA-M 0.000 description 1
• BTZBBPWCIZGBRF-UHFFFAOYSA-M sodium;4-methyl-3-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylbenzoate Chemical compound [Na+].CC1=CC=C(C([O-])=O)C=C1S(=O)(=O)N1C2=CC=CC=C2N=C1S(=O)CC1=NC=CC(OCC(F)(F)F)=C1C BTZBBPWCIZGBRF-UHFFFAOYSA-M 0.000 description 1
• RRFCKCAQHRITRG-UHFFFAOYSA-N sodium;5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-3-ide;hydrate Chemical compound O.[Na+].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C RRFCKCAQHRITRG-UHFFFAOYSA-N 0.000 description 1
• XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
• PVGBHEUCHKGFQP-UHFFFAOYSA-N sodium;n-[5-amino-2-(4-aminophenyl)sulfonylphenyl]sulfonylacetamide Chemical compound [Na+].CC(=O)NS(=O)(=O)C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 PVGBHEUCHKGFQP-UHFFFAOYSA-N 0.000 description 1
• 239000008259 solid foam Substances 0.000 description 1
• 239000002195 soluble material Substances 0.000 description 1
• 238000012453 sprague-dawley rat model Methods 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 210000005239 tubule Anatomy 0.000 description 1
• 230000007306 turnover Effects 0.000 description 1