WO2004077367A1 - Compose tetracyclique de sulfenamide - Google Patents
Compose tetracyclique de sulfenamide Download PDFInfo
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- WO2004077367A1 WO2004077367A1 PCT/JP2004/002107 JP2004002107W WO2004077367A1 WO 2004077367 A1 WO2004077367 A1 WO 2004077367A1 JP 2004002107 W JP2004002107 W JP 2004002107W WO 2004077367 A1 WO2004077367 A1 WO 2004077367A1
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- lower alkyl
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- hydrogen atom
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a tetracyclic sulfenamide compound having a proton pump inhibitory activity and useful as a therapeutic agent for peptic ulcer.
- histamine receptor antagonists represented by cimetidine, ranitidine, famotidine, nizatidine, oral xazidine, and omebrazole, esomebazole, lansoprazole, labebrazole, and pantoprazole are representatives.
- Gastric acid secretion inhibitors such as proton pump (H + ZK and ATPase) inhibitors have been used. These have a strong gastric acid secretion inhibitory effect and are widely used clinically because of their high therapeutic effect. Disclosure of the invention
- histamine H 2 receptor antagonists there antiandrogenic, for central operation, etc. and the like inhibitory activity of metabolic enzymes in the liver problems.
- R 1 is a lower alkyl group optionally substituted by a hydroxy group or a lower alkoxycarbonyl group, a lower acyl group optionally substituted by a halogen atom, a cyano group, a carbonyl group, a hydroxy group
- R 2 and R 4 are the same or different and represent a lower alkyl group, a lower alkoxy group or a hydrogen atom
- R 3 represents 1 to 8 halogen atoms, a hydroxy group
- 1 represents a lower alkyl group which may have a substituent selected from a lower alkoxy group, a furyl group and a morpholino group which may be substituted with from 8 to 8 halogen atoms
- A represents a benzene ring, a pyridine ring or Represents a thiophene ring
- B is a single bond, an amino group or one NR-(R is a halogen atom, a hydroxy group
- the present invention also provides a medicine containing the compound represented by the above formula (I).
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising the compound represented by the above formula (I) and a pharmaceutically acceptable carrier.
- the present invention provides a use of the compound represented by the above formula (I) for the manufacture of a medicament.
- the present invention provides a method for treating peptic ulcer, which comprises administering an effective amount of the compound represented by the above formula (I).
- lower means a straight, branched or cyclic carbon chain having 1 to 6 carbon atoms.
- lower alkyl group includes linear, branched or cyclic alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl.
- lower alkoxy group a linear, branched or cyclic alkoxy group having 1 to 6 carbon atoms, for example, methoxy group, ethoxy group, propoxy group, isopropoxy group, cyclopropoxy group, butoxy group, isobutoxy group , s ec - butoxy, tert - butoxy group, cyclobutoxy group, Penchiruokishi group, 1 one methylbutoxy group, 2-methylbutoxy group, isopentyl Ruo alkoxy group, tert- Penchiruokishi group, 1, 2-dimethyl propoxy group , Neopentyloxy, 1-ethylpropoxy, cyclopentyloxy, hexyloxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, iso- Xyloxy, 1-ethylbutoxy, 2_ethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutyl
- “Lower alkenyl group” means a straight-chain, branched or cyclic alkenyl group having 2 to 6 carbon atoms having 1 to 3 double bonds, for example, a pinyl group, a 1-propenyl group, Aryl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, 11-pentenyl, 2-pentenyl, 3-pentenyl, 41-pentenyl, cyclo Pentenyl group, 1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-1-hexenyl group, 5-hexenyl group, cyclohexyl Examples include a senyl group and a 1,3-butaenyl group. Among these, a more preferred lower alkenyl group is an alkenyl group having 2 to 4 carbon atoms and having one double bond.
- lower acetyl group refers to an acetyl group having 2 to 6 carbon atoms, and examples thereof include an acetyl group, a propionyl group, a butyryl group, an isoptyryl group, a valeryl group, an isovaleryl group, and a pivaloyl group. Of these, a more preferred lower acyl group is one having 2 to 5 carbon atoms.
- the "lower alkoxycarbonyl group” is a group formed by bonding the above-mentioned "lower alkoxy group” to a lower alkoxy group, such as a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, and an isopropoxycarbonyl group.
- the “lower alkylamino group” is a group in which one or two hydrogen atoms of an amino group are substituted with the above “lower alkyl group”, and examples thereof include a methylamino group, an ethylamino group, a propylamino group, an isopropylamino group, and a cycloalkyl group.
- halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and a more preferred halogen atom is a fluorine atom.
- the “furyl group” includes both a 2-furyl group and a 3-furyl group, and a more preferred furyl group is a 2-furyl group.
- hydroxyphenyl group means a group obtained by substituting a phenyl group with one hydroxy group, for example, a 0-hydroxyphenyl group (2-hydroxyphenyl group, 6-hydroxyphenyl group).
- a hydroxyphenyl group an m-hydroxyphenyl group (3-hydroxyphenyl group, 5-hydroxyphenyl group) and a p-hydroxyphenyl group (4-hydroxyphenyl group).
- the counteranion of the present invention is not particularly limited as long as it can form a pharmacologically acceptable compound.
- halogen ions such as fluorine ion, chloride ion, bromide ion, iodine ion, sulfate ion, nitrate ion, phosphate ion, tetrafluoroborate ion, or acetate ion, oxalate ion, malonate ion, succinic acid ion Ion, maleate ion, fumarate ion, lactate ion, malate ion, citrate ion, tartrate ion, methanesulfonic acid ion, ethanesulfonic acid ion and the like.
- R 1 in the compound (I) of the present invention a hydrogen atom, a hydroxy group, a lower alkyl group and a lower alkoxycarbonylalkyl group are preferred, and among them, a hydrogen atom and a hydroxy group are particularly preferred.
- R 2 is preferably a hydrogen atom, a lower alkyl group or a lower alkoxy group, and among them, a hydrogen atom is particularly preferable.
- R 3 is preferably a hydrogen atom, a lower alkyl group optionally substituted with 1 to 8 halogen atoms, or a lower alkoxyalkyl group optionally substituted with 1 to 8 halogen atoms, and more specifically.
- R 4 is preferably a hydrogen atom, a lower alkyl group or a lower alkoxy group, and more specifically, a hydrogen atom, a methyl group, Examples include an ethyl group, a methoxy group, and an ethoxy group.
- B is preferably a single bond, an amino group or one NR— (R represents a lower alkyl group which may be substituted by a hydroxy group), and more specifically, a single bond, an amino group, a methylamino group, Examples include an ethylamino group, a propylamino group, an isopropylamino group, a butylamino group, an isopropylamino group or an N- (2-hydroxyethyl) amino group.
- R represents a lower alkyl group which may be substituted by a hydroxy group
- the compound (I) of the present invention may exist in stereoisomers, and the present invention includes any of its optically active, racemic, and diastereomers.
- the compounds of the present invention also include solvates represented by hydrates.
- the compound (I) of the present invention can be produced, for example, by the following method.
- R 1 , R 2 , R 3 , R 4 , A and Z have the same meanings as described above, and X and X 1 each represent a halogen atom.
- Examples of the base used for the reaction between 1 H-benzimidazole-2-thiol (II) and the 2-substituted methylpyridine derivative (III) include sodium hydroxide, lithium hydroxide, potassium hydroxide and the like.
- Examples of the solvent include alcohols such as methanol and ethanol or hydrous alcohols thereof, aprotic solvents such as dimethyl sulfoxide and N, N-dimethylformamide, and ethers such as tetrahydrofuran and dioxane. It is preferably carried out by stirring at a reflux temperature for 1 to 24 hours.
- Bases used for the condensation of 18-logenopyridines (V) with alcohols (VI) include metals such as sodium hydride, lithium hydride, hydrogen hydride and the like, and metals such as lithium, sodium and potassium. , Potassium tert-butoxide, n-butyllithium, etc., in a solvent such as dimethylsulfoxide, N, N-dimethylformamide, dimethyloxyethylene, tetrahydrofuran, dioxane or an alcohol (VI) as a solvent, from room temperature to reflux temperature. It is preferable to carry out by stirring for 1 to 24 hours.
- the oxidation reaction of the methylthiobenzimidazole (IV) is carried out using organic peracids such as Hi-chloroperbenzoic acid and peracetic acid, sodium metaperiodate, cumene hydroperoxide, tert-butoxyperoxide. It is preferable to use alcohol peroxide such as aqueous hydrogen peroxide, 0X0NE (manufactured by Dubon), or the like, in a solvent such as methylene chloride, chloroform, N, N-dimethylformamide, toluene, and ethyl acetate. It is preferable to carry out the stirring by stirring at 50 ° C. for 10 minutes to 24 hours.
- organic peracids such as Hi-chloroperbenzoic acid and peracetic acid, sodium metaperiodate, cumene hydroperoxide, tert-butoxyperoxide.
- alcohol peroxide such as aqueous hydrogen peroxide, 0X0NE (manufactured by
- the compound is one of the compounds of the present invention.
- (la) is obtained.
- alcohols such as methanol and ethanol are used, and as the acid comprising a counter anion and a hydrogen atom, borofluoric acid, hydrochloric acid and the like can be mentioned.
- the reaction is preferably carried out by stirring under cooling or at room temperature for 30 minutes to 2 hours. ⁇
- the methylthiobenzimidazole derivative (IV) is reacted with N-tert-butoxycarboxyl 3- (4-cyanophenyl) oxaziridine and then subjected to conventional solvent decomposition to give 1-N-aminobenzide.
- imidazoles (VIII) The reaction is carried out according to a known method .0 ⁇ .0 ⁇ 111., 58,4791 (1993) or 16 ⁇ &] 16 0111 ⁇ "., 36,1439 (1995).
- the benzimidazoles (VIII) are converted to methylsulfinyl 11N-aminobenzimidazoles (IX) by the same operation as the above oxidation reaction, and furthermore, by the reaction of Kaun Yunani anion with an acid consisting of a hydrogen atom.
- (Lb) which is one of the compounds of the present invention can be obtained.
- R 5 is a halogen atom, a hydroxy group, a phenyl group, a hydroxyphenyl group, an amino group, a lower alkoxy group, a lower alkoxycarbonyl group, or a lower alkoxycarbonyl group.
- Ru is selected from alkylamino group show a lower alkyl group or a lower alkenyl group or a hydrogen atom
- R 6 represents a benzyl O carboxymethyl Cal Poni group or ter Bok butoxycarbonyl two Le group
- R 7 Represents a lower alkyl group which may have a substituent selected from a halogen atom, a hydroxy group, a phenyl group, a hydroxyphenyl group, an amino group, a lower alkoxy group, a lower alkoxycarbonyl group and a lower alkylamino group. Represents a lower alkenyl group.
- a benzyloxycarbonyl group or a tert-butoxycarbonyl group is added to the terminal amino group of hydrazines (X) to give (XI), the nitro group is reduced, and then in the presence of carbon disulfide and a base.
- mercaptoimidazoles (XII) can be obtained by reacting in the presence of a complex such as thiophene dimethyl xanthate.
- a complex such as thiophene dimethyl xanthate.
- the base used in the reaction sodium hydroxide, potassium heptaoxide and the like are used, and as the solvent, alcohols such as methanol and ethanol are used.
- the reaction is preferably carried out by stirring at room temperature to reflux temperature for 1 to 24 hours.
- the compound (XIII) is obtained by reacting mercaptoimidazoles (XII) with 2-chloromethylpyridines in the presence of a base.
- a base lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. are used.
- alcohols such as methanol, ethanol and the like, or hydrated alcohols thereof, dimethyl sulfoxide, N Protic solvents such as N, N-dimethylformamide and the like, and ethers such as tetrahydrofuran and dioxane are used.
- the reaction is preferably carried out by stirring at room temperature to reflux temperature for 1 to 24 hours.
- Compound (XI II) is converted to (XV) via (XVI) by reductive alkylation.
- Can be The reaction is carried out by using an acid such as hydrochloric acid or trifluoroacetic acid or a base in a solvent such as ethers, alcohols or hydrous alcohols using the benzyloxycarponyl group or tert-butoxycarpoxyl group of (XI II).
- (XVI) after deprotection using a catalytic reduction reaction, and then (XVI) is converted to aldehydes such as formaldehyde and acetate aldehyde or ketones such as acetone and methyl ethyl ketone in the presence of an acid catalyst.
- a reducing agent It is carried out by reacting and further reducing with a reducing agent.
- the solvent used in the reaction include alcohols such as methanol and ethanol, ethers such as dimethyl ether, diisopropyl ether, tetrahydrofuran, and dioxane, acetonitrile, and water-containing solvents thereof. Hydrochloric acid or the like is used, and sodium borohydride, sodium cyanoborohydride or the like is used as a reducing agent.
- the reaction can be carried out at 0 ° (: up to 60 ° C).
- Compound (XI II) is subjected to a substitution reaction with an amino group at the 11-N position, if necessary, followed by deprotection of a benzyloxycarbonyl group or a tert-butoxycarbonyl group, whereby the compound (XI II) is obtained.
- XV Examples of the substitution reaction include known alkylation reactions, and the corresponding alkyl halides in a solvent such as dimethyl sulfoxide or N, N-dimethylformamide in the presence of a base such as sodium hydride or potassium hydride. The reaction is carried out. The reaction is usually performed at room temperature to 60 ° C.
- the compound ( ⁇ ), (XV) or (XVI) obtained above is subjected to an oxidation reaction to obtain a sulfoxide form (XVI I).
- the reaction is performed with organic peracids such as m-chloroperbenzoic acid and peracetic acid, sodium metaperiodate, cumene hydroperoxide, tert-butoxyperoxide, alcohol peroxides such as hydrogen peroxide, OX ON E ( 10 minutes at 0 to 50 ° C in a solvent such as methylene chloride, chloroform, N, N-dimethylformamide, toluene, ethyl acetate, or a mixture thereof. It is preferable to carry out by stirring for ⁇ 24 hours.
- the thus-obtained compound of the present invention has an excellent proton pump inhibitory action as described below, and thus is useful as a therapeutic agent for peptic ulcer.
- the compound of the present invention When the compound of the present invention is administered as a therapeutic agent for peptic ulcer, it may be administered orally as a powder, granules, capsules, oral tablets, suppositories, injections, or external use. It may be administered parenterally as an agent or infusion.
- the dosage varies depending on the degree of symptoms, age, type of ulcer, etc., but is usually about 0.01 to 200 mgZkg per day, preferably 0.05 to 50 mgZkg, more preferably 0.1 to 50 mgZkg. : Administer L OmgZkg once or several times a day.
- an excipient and, if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, etc. are added to the active substance, and then a conventional method is used. Tablets, coated tablets, granules, powders, capsules, etc.
- Excipients include, for example, lactose, corn starch, sucrose, glucose, sorbite, crystalline cellulose, silicon dioxide, etc.
- binders include, for example, polyvinyl alcohol, polyvinyl ether, ethylcellulose, methylcellulose, arabia gum, tragacanth, Gelatin, shellac, hydroxypropyl cellulose Disintegrants such as starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, hydrogen carbonate, thorium, calcium citrate, dextrin, pectin, etc.
- a lubricant for example, magnesium stearate, talc, polyethylene glycol, silica, hydrogenated vegetable oil, etc.
- oral solid preparations can be prepared as enteric preparations using a covering base such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate and methacrylate copolymer.
- a covering base such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate and methacrylate copolymer.
- these tablets and granules may be sugar-coated, gelatin-coated, or appropriately coated as necessary.
- a pH adjuster When preparing an injection, a pH adjuster, a buffer, a stabilizing agent, a solubilizing agent, and the like are added to the main drug, if necessary, and a subcutaneous, intramuscular, or intravenous injection is prepared by a conventional method.
- a pH adjuster When preparing an injection, a pH adjuster, a buffer, a stabilizing agent, a solubilizing agent, and the like are added to the main drug, if necessary, and a subcutaneous, intramuscular, or intravenous injection is prepared by a conventional method.
- Example 1 2-[[3-Methoxy_4- (4,4,4-trifluorobutoxy) pyridin-2-yl] methylsulfinyl] benzimidazol sodium was replaced with 2-[[3-methoxy_ 4_ [2- (2,2,2-Trifluoro mouth ethoxy) ethoxy] pyridine-12-yl] methylsulfinyl] benzimidazolnatridium was used to give the title compound.
- Example 1 2-[[3-methoxy_4_ (4,4,4-trifluorobutoxy) pyridine-2-yl] methylsulfinyl] benzimidazo-l- sodium was replaced with 2 _ [[4-1-1 (4, 4,4-Trifluorobutoxy) pyridine-12-yl] methylsulfinyl] benzimidazol sodium, and the same operation as above using concentrated hydrochloric acid instead of borohydrofluoric acid to give the title compound Got.
- Example 1 2-[[3-methoxy-4- (4,4,4-trifluorobutoxy) pyridine-2-yl] methylsulfinyl] benzimidazol sodium was replaced with 2-[[4- [2 — (2,2,2-Trifluoroethoxy) ethoxy] pyridine-12-yl] methylsulfinyl] benzimidazole sodium and the same procedure using concentrated hydrochloric acid instead of borofluoric acid. This gave the title compound.
- Example 5 1-amino-2 _ [[3-methyl-4_ (2,2,2-trifluoroethoxy) pyridin-2-yl] methylsulfinyl] benzimidazole was replaced by 1-methylamino-2 — [[3-Methyl-41- (2,2,2-trifluoroethoxy) pyridin-2-yl] methylsulfinyl] benzimidazole was used to give the title compound. .
- Example 5 1-amino-1 2-[[3-methyl-4- (2,2,2-trifluoroethoxy) pyridine-2-yl] methyl ⁇ / sulfinyl] instead of benzimidazole 1-isobutylamino-2-[[3-methyl_4_ (2,2,2-trifluoroethoxy) pyridine-2-yl] methylsulfinyl] benzimidazole The title compound was obtained.
- Example 6 1-amino-5 (6) -hydroxy-2-[[3-methyl-14- (2,2,2-trifluoroethoxy) pyridine-2-yl] methylsulfinyl] benzimidazole Perform the same operation using 1-amino-2-[[3-methyl-4-1 (2,2,2-trifluoroethoxy) pyridin-2-yl] methylsulfinyl] benzimidazole instead Afforded the title compound.
- Example 5 1-amino-2-[[3-methyl-4-1 (2,2,2-trifluoroethoxy) pyridine-12-yl] methylsulfinyl] -benzimidazole was replaced with 1-amino-2- The same procedure was performed using [[3-methoxy-41 (4,4,4-trifluorobutoxy) pyridine_2-2-yl] methylsulfinyl] benzimidazole to give the title compound.
- Tris-HCl buffer On excitation 1 ZL Tris-HCl buffer After crushing using a mixer in pH 7.4 (hereinafter abbreviated as Tris-HCl buffer), the mixture was centrifuged at 9000 Xg for 30 minutes. The supernatant was gently overlaid on 8 mL of 20 ml of olZL Tris-HCl buffer, pH 7.4, containing 30% sucrose and ImmolZL EGTA, and ultracentrifuged at lOOOO Xg for 60 minutes.
- the interface fraction obtained by centrifugation was collected, and centrifugation was repeated twice at 113000 Xg for 60 minutes. After suspending the precipitate in Tris-HCl buffer, homogenize at low speed. The homogenized product was used as an enzyme sample and stored frozen at 180 ° C. The obtained sample was quantified for its protein content using the BCA protein atssay reagent using the method of Smith et al. (Anal. Biochem., 150, 76-85 (1985)). All of the above operations are performed under water cooling ft.
- H + / K +-ATPase inhibitory activity is based on a method using ATP as a substrate and a method for quantifying the amount of inorganic phosphorus as a degradation product (Biochem. Biophys. Res. Coramun., 40, 880-886 (1970)).
- I went according to it.
- a hydrochloric acid solution for pre-treating the test compound a 1 ⁇ 1 O— ⁇ olZL (pH 1) hydrochloric acid solution containing 50% DMS0 was used in consideration of the solubility of the test compound. The test compound at each concentration was added to this hydrochloric acid solution so as to be diluted 1000 times, and left at room temperature for 15 minutes.
- the measurement was performed in duplicate, and the residual activity was determined from the difference between the average value of the amount of inorganic phosphorus in the presence of KC1 and the amount of inorganic phosphorus in the absence of ⁇ C1, and the activity of the control value (DMS0) was taken as 100% to determine the inhibition rate of the compound. Calculated. IC 5 as each test compound inhibition strength. The value was calculated and displayed. All test compounds were dissolved in dimethyl sulfoxide immediately before use. As a result, the compound of Example 1 had IC 5 . The value is 1.28 28, The compound of Example 2 has an IC 5Q value of 1.51 M, and the compound of Example 3 has an IC 5 of 5 . The value is 2.68 U, and the compound of Example 4 has IC 5 . The value of 5.89 ⁇ The compound of Example 10 has IC 5 . The value is 5.09 ⁇ .
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Abstract
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JP2003046736A JP2006188432A (ja) | 2003-02-25 | 2003-02-25 | 四環系スルフェンアミド化合物 |
JP2003-046736 | 2003-02-25 |
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Cited By (1)
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WO2008047681A1 (fr) * | 2006-10-13 | 2008-04-24 | Eisai R & D Management Co., Ltd. | Benzimidazole présentant une activité inhibitrice de la sécrétion d'acide gastrique |
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JPH1017471A (ja) * | 1996-07-04 | 1998-01-20 | Yoshitomi Pharmaceut Ind Ltd | ピリジン化合物系併用医薬 |
WO2000009498A1 (fr) * | 1998-08-10 | 2000-02-24 | Partnership Of Michael E. Garst, George Sachs And Jai Moo Shin | Promedicaments d'inhibiteurs de la pompe a protons |
WO2003024957A1 (fr) * | 2001-09-18 | 2003-03-27 | Zeria Pharmaceutical Co., Ltd. | Derives de benzimidazole |
WO2003082854A1 (fr) * | 2002-03-29 | 2003-10-09 | Zeria Pharmaceutical Co., Ltd. | Derives 1-n-aminobenzimidazole |
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JPS617281A (ja) * | 1984-06-13 | 1986-01-13 | アクチエボラゲツト・ヘツスレ | 新規なスルフエンアミド |
JPS62277392A (ja) * | 1986-02-13 | 1987-12-02 | Takeda Chem Ind Ltd | スルフエンアミド誘導体およびその製造法 |
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WO2008047681A1 (fr) * | 2006-10-13 | 2008-04-24 | Eisai R & D Management Co., Ltd. | Benzimidazole présentant une activité inhibitrice de la sécrétion d'acide gastrique |
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