ES2263028T3 - Derivados de bencimidazol y su uso como profarmacos de inhibidores de bomba de proton. - Google Patents
Derivados de bencimidazol y su uso como profarmacos de inhibidores de bomba de proton.Info
- Publication number
- ES2263028T3 ES2263028T3 ES03765694T ES03765694T ES2263028T3 ES 2263028 T3 ES2263028 T3 ES 2263028T3 ES 03765694 T ES03765694 T ES 03765694T ES 03765694 T ES03765694 T ES 03765694T ES 2263028 T3 ES2263028 T3 ES 2263028T3
- Authority
- ES
- Spain
- Prior art keywords
- acid
- sulfonyl
- mixture
- compound
- methoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229940126409 proton pump inhibitor Drugs 0.000 title description 36
- 239000000612 proton pump inhibitor Substances 0.000 title description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 271
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
- 150000003536 tetrazoles Chemical group 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 14
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 3
- 239000003814 drug Substances 0.000 claims description 53
- 229940079593 drug Drugs 0.000 claims description 51
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 385
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 349
- 239000000543 intermediate Substances 0.000 description 342
- 239000000203 mixture Substances 0.000 description 332
- -1 benzimidazole sulfoxide Chemical class 0.000 description 309
- 239000002253 acid Substances 0.000 description 274
- 239000007787 solid Substances 0.000 description 185
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 185
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 152
- 239000000243 solution Substances 0.000 description 147
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 136
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 118
- 238000006243 chemical reaction Methods 0.000 description 104
- 230000002829 reductive effect Effects 0.000 description 90
- 239000011541 reaction mixture Substances 0.000 description 72
- 239000006260 foam Substances 0.000 description 68
- 150000002148 esters Chemical class 0.000 description 65
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 62
- 239000012074 organic phase Substances 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- 239000011734 sodium Substances 0.000 description 57
- 235000017557 sodium bicarbonate Nutrition 0.000 description 57
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 53
- 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 53
- 229910052708 sodium Inorganic materials 0.000 description 53
- 159000000000 sodium salts Chemical class 0.000 description 48
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 45
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000000741 silica gel Substances 0.000 description 41
- 229910002027 silica gel Inorganic materials 0.000 description 41
- 229940002612 prodrug Drugs 0.000 description 38
- 239000000651 prodrug Substances 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 239000000706 filtrate Substances 0.000 description 37
- 239000000463 material Substances 0.000 description 37
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 34
- 238000004440 column chromatography Methods 0.000 description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 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 33
- 239000008346 aqueous phase Substances 0.000 description 32
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 238000001914 filtration Methods 0.000 description 30
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 30
- 238000001704 evaporation Methods 0.000 description 29
- 230000008020 evaporation Effects 0.000 description 29
- 238000010992 reflux Methods 0.000 description 29
- 239000002244 precipitate Substances 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 239000012071 phase Substances 0.000 description 23
- 239000000047 product 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
- 238000003756 stirring Methods 0.000 description 23
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 21
- 230000001376 precipitating effect Effects 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 19
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- 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 16
- 238000000034 method Methods 0.000 description 16
- 239000011833 salt mixture Substances 0.000 description 16
- 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 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 15
- 239000008241 heterogeneous mixture Substances 0.000 description 15
- 150000004702 methyl esters Chemical class 0.000 description 15
- 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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 13
- 230000007062 hydrolysis Effects 0.000 description 13
- 238000006460 hydrolysis reaction Methods 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- 150000003462 sulfoxides Chemical class 0.000 description 13
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 12
- 230000002496 gastric effect Effects 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
- 239000000725 suspension 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
- ABDMQSFNJPYOLA-UHFFFAOYSA-N NS(=O)(=O)[N+]([O-])=O Chemical compound NS(=O)(=O)[N+]([O-])=O ABDMQSFNJPYOLA-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 10
- 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
- 230000006870 function Effects 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 description 10
- 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 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 9
- 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 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229940125797 compound 12 Drugs 0.000 description 9
- 230000027119 gastric acid secretion Effects 0.000 description 9
- 239000002198 insoluble material Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 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
- 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 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 229940125782 compound 2 Drugs 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 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 7
- HBDKFZNDMVLSHM-UHFFFAOYSA-N 2-(pyridin-2-ylmethylsulfinyl)-1h-benzimidazole Chemical class N=1C2=CC=CC=C2NC=1S(=O)CC1=CC=CC=N1 HBDKFZNDMVLSHM-UHFFFAOYSA-N 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 7
- 229940126214 compound 3 Drugs 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
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid group Chemical group C(CCCCC)(=O)O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 229940001584 sodium metabisulfite Drugs 0.000 description 7
- 235000010262 sodium metabisulphite Nutrition 0.000 description 7
- 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 6
- FNTPEVNXQNLYKO-UHFFFAOYSA-N 2-[4-[2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]acetic acid Chemical compound COCCCOC1=CC=NC(CS(=O)C=2N(C3=CC=CC=C3N=2)S(=O)(=O)C=2C=CC(OCC(O)=O)=CC=2)=C1C FNTPEVNXQNLYKO-UHFFFAOYSA-N 0.000 description 6
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 6
- LMRKXSDOAFUINK-UHFFFAOYSA-N 3-chlorosulfonylbenzoic acid Chemical compound OC(=O)C1=CC=CC(S(Cl)(=O)=O)=C1 LMRKXSDOAFUINK-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 229940125851 compound 27 Drugs 0.000 description 6
- 229940125878 compound 36 Drugs 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-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
- XZFISDJHLFXCLR-UHFFFAOYSA-N 6-[[2-[4-[2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]benzimidazol-1-yl]sulfonylphenoxy]acetyl]amino]hexanoic acid Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(OCC(=O)NCCCCCC(O)=O)C=C1 XZFISDJHLFXCLR-UHFFFAOYSA-N 0.000 description 5
- 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 5
- 108010083204 Proton Pumps Proteins 0.000 description 5
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 5
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 201000006549 dyspepsia Diseases 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000012258 stirred mixture Substances 0.000 description 5
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- QDTQEKSCNKGNCD-UHFFFAOYSA-N methyl 2,2-dimethyl-3-(4-methylphenyl)sulfonyloxypropanoate Chemical compound COC(=O)C(C)(C)COS(=O)(=O)C1=CC=C(C)C=C1 QDTQEKSCNKGNCD-UHFFFAOYSA-N 0.000 description 1
- BZCKRPHEZOHHBK-UHFFFAOYSA-N methyl 2-phenoxyacetate Chemical compound COC(=O)COC1=CC=CC=C1 BZCKRPHEZOHHBK-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- AVSKEEJRUZCTHJ-UHFFFAOYSA-N n-(2-amino-5-methoxyphenyl)sulfamoyl chloride Chemical compound COC1=CC=C(N)C(NS(Cl)(=O)=O)=C1 AVSKEEJRUZCTHJ-UHFFFAOYSA-N 0.000 description 1
- FWCSTBKUAHLACW-UHFFFAOYSA-N n-(4-methoxy-2-nitrophenyl)sulfamoyl chloride Chemical class COC1=CC=C(NS(Cl)(=O)=O)C([N+]([O-])=O)=C1 FWCSTBKUAHLACW-UHFFFAOYSA-N 0.000 description 1
- JFRSAGFOHWLGSD-UHFFFAOYSA-N n-(5-methoxy-2-nitrophenyl)sulfamoyl chloride Chemical class COC1=CC=C([N+]([O-])=O)C(NS(Cl)(=O)=O)=C1 JFRSAGFOHWLGSD-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 230000024717 negative regulation of secretion Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 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
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 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 1
- 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 1
- ADCIPEINXSDZLJ-UHFFFAOYSA-M sodium;3-[6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-yl]sulfonyl-4-methylbenzoate 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([O-])=O)=CC=C1C ADCIPEINXSDZLJ-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
- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000012265 solid product 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
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001544 thienyl group Chemical group 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
- 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
- 230000001960 triggered effect Effects 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
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39745902P | 2002-07-19 | 2002-07-19 | |
| US397459P | 2002-07-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2263028T3 true ES2263028T3 (es) | 2006-12-01 |
Family
ID=30771064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03765694T Expired - Lifetime ES2263028T3 (es) | 2002-07-19 | 2003-07-15 | Derivados de bencimidazol y su uso como profarmacos de inhibidores de bomba de proton. |
Country Status (22)
| Country | Link |
|---|---|
| US (3) | US6897227B2 (enExample) |
| EP (1) | EP1556371B1 (enExample) |
| JP (1) | JP4463103B2 (enExample) |
| KR (2) | KR100822981B1 (enExample) |
| AT (1) | ATE323695T1 (enExample) |
| AU (1) | AU2003259154B2 (enExample) |
| BR (1) | BR0312802A (enExample) |
| CA (1) | CA2492718C (enExample) |
| CO (1) | CO5690576A2 (enExample) |
| DE (1) | DE60304726T2 (enExample) |
| DK (1) | DK1556371T3 (enExample) |
| ES (1) | ES2263028T3 (enExample) |
| IL (1) | IL166371A0 (enExample) |
| MX (1) | MXPA05000657A (enExample) |
| NO (1) | NO20050801L (enExample) |
| NZ (1) | NZ538221A (enExample) |
| PL (1) | PL375255A1 (enExample) |
| PT (1) | PT1556371E (enExample) |
| RU (1) | RU2292342C2 (enExample) |
| TW (1) | TW200502231A (enExample) |
| WO (1) | WO2004009583A2 (enExample) |
| ZA (1) | ZA200501116B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6852739B1 (en) * | 1999-02-26 | 2005-02-08 | Nitromed Inc. | Methods using proton pump inhibitors and nitric oxide donors |
| AU2003254282A1 (en) * | 2002-08-01 | 2004-02-23 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| EP1644352A1 (en) * | 2003-07-15 | 2006-04-12 | Allergan, Inc. | Process for preparing isomerically pure prodrugs of proton pump inhibitors |
| WO2005039640A1 (en) * | 2003-10-03 | 2005-05-06 | Allergan Inc. | Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump inhibitor prodrugs |
| US20050075371A1 (en) * | 2003-10-03 | 2005-04-07 | Allergan, Inc. | Methods and compositions for the oral administration of prodrugs of proton pump inhibitors |
| CA2557471A1 (en) * | 2004-02-18 | 2005-09-09 | Allergan, Inc. | Methods and compositions for the intravenous administration of compounds related to proton pump inhibitors |
| EP1715861A2 (en) * | 2004-02-18 | 2006-11-02 | Allergan, Inc. | Compositions comprising prodrugs of proton pump inhibitors |
| BRPI0507796A (pt) * | 2004-03-11 | 2007-07-17 | Allergan Inc | métodos e composições para o tratamento de condições relacionadas com a secreção de ácido gástrico |
| ATE437869T1 (de) | 2004-04-28 | 2009-08-15 | Hetero Drugs Ltd | Verfahren zur herstellung von pyridinylmethyl-1h- benzimidazolverbindungen in enantiomerenangereicherter form oder als einzelne enantiomere |
| WO2007073301A1 (en) * | 2005-12-23 | 2007-06-28 | Astrazeneca Ab | Benzoimidazole derivatives as prodrugs of proton pump inhibitors |
| WO2007081871A1 (en) * | 2006-01-10 | 2007-07-19 | Allergan, Inc. | Therapeutic salt compositions of sulfonyl ester prodrugs of proton pump inhibitors and methods for their preparation |
| BRPI0711048A2 (pt) * | 2006-05-09 | 2011-08-23 | Astrazeneca Ab | formulações parenteral esterilizada e sólida estáveis, solução para administração parenteral, processos para a preparação de uma formulação e para a fabricação de um produto, método para prevenir ou tratar doenças gastrintestinais, uso de uma formulação sólida estável |
| US20070293543A1 (en) * | 2006-06-19 | 2007-12-20 | Edward Lee | THRESHOLD BLOOD OMEPRAZOLE CONCENTRATION IS 50 NG/ML FOR THE MAINTENANCE OF INTRAGASTRIC pH OF AT LEAST 4.0 AFTER ORAL DOSING WITH CMA-OMEPRAZOLE, AGN 201904-Z |
| US20100113524A1 (en) * | 2006-09-19 | 2010-05-06 | Garst Michael E | Prodrugs of proton pump inhibitors including the (1h-pyrrol-1-yl)-1h-benzimidazole moiety |
| US20100317689A1 (en) * | 2006-09-19 | 2010-12-16 | Garst Michael E | Prodrugs of proton pump inhibitors including the 1h-imidazo[4,5-b] pyridine moiety |
| EP2193518A4 (en) * | 2007-10-05 | 2010-10-27 | Lg Electronics Inc | PLASMA DISPLAY DEVICE |
| KR20090035195A (ko) * | 2007-10-05 | 2009-04-09 | 엘지전자 주식회사 | 플라즈마 디스플레이 장치 |
| KR100895333B1 (ko) * | 2007-11-01 | 2009-05-07 | 엘지전자 주식회사 | 플라즈마 디스플레이 패널의 구동 방법 및 그를 이용한플라즈마 디스플레이 장치 |
| WO2012051036A1 (en) | 2010-10-11 | 2012-04-19 | Merck Sharp & Dohme Corp. | Quinazolinone-type compounds as crth2 antagonists |
| WO2012087872A1 (en) | 2010-12-23 | 2012-06-28 | Merck Sharp & Dohme Corp. | Quinolines and aza-quinolines as crth2 receptor modulators |
| KR20130133219A (ko) | 2010-12-23 | 2013-12-06 | 머크 샤프 앤드 돔 코포레이션 | Crth₂ 수용체 조절제로서의 퀴녹살린 및 아자-퀴녹살린 |
| EP3242664A4 (en) * | 2015-01-09 | 2018-06-20 | The Regents of the University of California | Compositions and methods for treating gastrointestinal infections |
| CN108997177A (zh) * | 2018-09-04 | 2018-12-14 | 邵阳学院 | 一种微波促进n-苯磺酰基硝基苯胺类化合物合成的方法 |
Family Cites Families (20)
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| US430042A (en) * | 1890-06-10 | Valve | ||
| SE416649B (sv) * | 1974-05-16 | 1981-01-26 | Haessle Ab | Forfarande for framstellning av foreningar som paverkar magsyrasekretionen |
| SE7804231L (sv) * | 1978-04-14 | 1979-10-15 | Haessle Ab | Magsyrasekretionsmedel |
| 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 |
| 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 |
| SE8505112D0 (sv) * | 1985-10-29 | 1985-10-29 | Haessle Ab | Novel pharmacological compounds |
| NZ234564A (en) * | 1986-11-21 | 1991-04-26 | Haessle Ab | 1-substituted benzimidazoles and pharmaceutical compositions |
| US4758597A (en) * | 1987-05-15 | 1988-07-19 | University Patents, Inc. | Carenadiol and derivatives |
| US4965269A (en) * | 1989-12-20 | 1990-10-23 | Ab Hassle | Therapeutically active chloro substituted benzimidazoles |
| US5045522A (en) * | 1990-03-27 | 1991-09-03 | Phillips Petroleum Company | Absorption composition comprising zinc titanate for removal of hydrogen sulfide from fluid streams |
| PL166209B1 (pl) * | 1990-06-20 | 1995-04-28 | Astra Ab | Sposób wytwarzania nowych pochodnych benzimidazolu PL |
| SE9301830D0 (sv) * | 1993-05-28 | 1993-05-28 | Ab Astra | New compounds |
| NZ288609A (en) * | 1994-06-10 | 1998-12-23 | Byk Gulden Lomberg Chem Fab | Substituted (4-thiopyridinyl) methylthio-benzimidazole (or 1h-imidazo-[2,3-b]-pyridine) and medicaments |
| US5708017A (en) * | 1995-04-04 | 1998-01-13 | Merck & Co., Inc. | Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors |
| CN100396675C (zh) * | 1998-08-10 | 2008-06-25 | 加利福尼亚州大学董事会 | 质子泵抑制剂的前药 |
| US6093734A (en) * | 1998-08-10 | 2000-07-25 | Partnership Of Michael E. Garst, George Sachs, And Jai Moo Shin | Prodrugs of proton pump inhibitors |
| EP1535921A1 (en) * | 1998-08-12 | 2005-06-01 | Gilead Sciences, Inc. | Method of manufacture of 1,3-oxathiolane nucleosides |
| SE0002476D0 (sv) | 2000-06-30 | 2000-06-30 | Astrazeneca Ab | New compounds |
| US6599167B2 (en) * | 2000-09-27 | 2003-07-29 | Glenn Waltz | Game call holder and amplifying device |
| US20040039027A1 (en) | 2000-10-12 | 2004-02-26 | Keiji Kamiyama | Benzimidazole compounds, process for producing the same and use thereof |
-
2003
- 2003-07-15 ES ES03765694T patent/ES2263028T3/es not_active Expired - Lifetime
- 2003-07-15 WO PCT/US2003/022419 patent/WO2004009583A2/en not_active Ceased
- 2003-07-15 CA CA2492718A patent/CA2492718C/en not_active Expired - Lifetime
- 2003-07-15 AT AT03765694T patent/ATE323695T1/de not_active IP Right Cessation
- 2003-07-15 RU RU2005105564/04A patent/RU2292342C2/ru not_active IP Right Cessation
- 2003-07-15 MX MXPA05000657A patent/MXPA05000657A/es active IP Right Grant
- 2003-07-15 US US10/620,252 patent/US6897227B2/en not_active Expired - Lifetime
- 2003-07-15 KR KR1020067026729A patent/KR100822981B1/ko not_active Expired - Fee Related
- 2003-07-15 PL PL03375255A patent/PL375255A1/xx not_active Application Discontinuation
- 2003-07-15 DK DK03765694T patent/DK1556371T3/da active
- 2003-07-15 EP EP03765694A patent/EP1556371B1/en not_active Expired - Lifetime
- 2003-07-15 DE DE60304726T patent/DE60304726T2/de not_active Expired - Lifetime
- 2003-07-15 BR BR0312802-4A patent/BR0312802A/pt not_active IP Right Cessation
- 2003-07-15 AU AU2003259154A patent/AU2003259154B2/en not_active Ceased
- 2003-07-15 JP JP2004523537A patent/JP4463103B2/ja not_active Expired - Fee Related
- 2003-07-15 PT PT03765694T patent/PT1556371E/pt unknown
- 2003-07-15 KR KR1020057000899A patent/KR100788778B1/ko not_active Expired - Fee Related
- 2003-07-15 NZ NZ538221A patent/NZ538221A/en unknown
- 2003-11-07 TW TW092131253A patent/TW200502231A/zh unknown
-
2005
- 2005-01-18 IL IL16637105A patent/IL166371A0/xx unknown
- 2005-01-20 US US11/039,631 patent/US20050143423A1/en not_active Abandoned
- 2005-01-20 US US11/039,630 patent/US20050182101A1/en not_active Abandoned
- 2005-02-08 ZA ZA200501116A patent/ZA200501116B/xx unknown
- 2005-02-15 CO CO05013468A patent/CO5690576A2/es not_active Application Discontinuation
- 2005-02-15 NO NO20050801A patent/NO20050801L/no not_active Application Discontinuation
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