- Mechanism of inhibition of H+, K+-ATPase by sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810)
-
Sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810) and omeprazole inhibit gastric acid secretion through inhibition of the activity of H+, K+-ATPase present in parietal cell membrane vesicles, by chemical modification of SH groups in the enzyme molecule. In order to clarify the mechanism of the chemical modification, reaction products of E3810 and omeprazole with 2-mercaptoethanol under acidic conditions (pH 3, 4, 5, 6) were isolated by HPLC, and subjected to structural analysis by UV, 1H-NMR and mass spectrometry. E3810 and omeprazole appeared to undergo two kinds of reactions, affording disulfide-type products (type I reaction) and sulfide-type products (type II reaction). The rates of these reactions were determined by HPLC, and the stability of the products in the presence and absence of glutathione was investigated. In the case of E3810, type I reaction was found to proceed faster than type II reaction at every pH value studied. The type I reaction of E3810 was faster than that of omeprazole. The rate of type I reaction decreased at pH 5 and 6, especially for omeprazole, and the contribution of type II reaction increased as the pH of the reaction mixture was increased. The sulfide-type modification products were stable, whereas the formation of the disulfide-type modification products was reversed by the action of endogenous SH compounds such as glutathione. These results suggest that higher inhibitory activity of E3810 against gastric acid secretion and faster recovery of the enzyme activity after inhibition by E3810 can be expected, as compared with those of omeprazole.
- Nochi, Shigeharu,Yokoyama, Yumi,Narukawa, Megumi,Ebine, Kumiko,Murahashi, Miho,Kawakami, Yoshiyuki,Asakawa, Naoki,Sato, Tadashi
-
-
Read Online
- Ureido-containing benzoimidazole compounds and application thereof
-
The invention belongs to the technical field of medicines, and relates to ureido-containing benzoimidazole compounds, a preparation method thereof, and an application of the ureido-containing benzoimidazole compounds in preparing medicines for anti-tumor
- -
-
Paragraph 0039-0041
(2019/08/20)
-
- Amide-containing benzimidazole compound and application thereof (by machine translation)
-
The invention belongs to the technical field of medicines, and relates to 2 - [(pyridin -2 -ylmethyl) thio] - 111H-benzimidazole compounds as well as a preparation method and application. The general formula 2 - [(pyridin -2 -ylmethyl) thio] - 111H-benzimidazole compound and pharmaceutically acceptable salt are shown as follows: R1 , R2 The same or different, selected from hydrogen, C1 - C8 alkyl, C3 - C6 cycloalkyl, phenyl, halo substituted phenyl, C1 - C4 alkyl substituted phenyl, halo and C1 - C4 alkoxy at the same time substituted phenyl, halo substituted C1 C1 - C4 - C4 alkyl C1 - C4 substituted phenyl, benzyl, 4 - benzyloxyphenyl; or R1 , R2 A substituted or unsubstituted morpholinyl, phenylpiperazine or diphenylmethyl piperazine together with the nitrogen atom to which they are attached; the substituents are C1 - C4 alkoxy, C1 - C4 alkyl, halogen; R3 , R5 Self H, C1 - C4 alkyl. The compound is simple and convenient, is suitable for industrial production, and has obvious antitumor activity. (by machine translation)
- -
-
Paragraph 0064; 0065; 0066
(2019/07/29)
-
- Metal- and base-free regioselective thiolation of the methyl C(sp3)-H bond in 2-picoline: N -oxides
-
A one-pot, two-step synthesis of pyridine-2-ylmethyl thioethers is developed through a TFAA-mediated [3,3]-sigmatropic rearrangement of pyridine N-oxides and TBAB-catalyzed direct conversion of trifluoroacetates into thioethers under metal- and base-free conditions. This methodology enables thiolation of the unactivated methyl C(sp3)-H bond in 2-picolines with thiols. Remarkable features of the method include high regioselectivity, step- and atom-economy, mild conditions, simple operation, wide substrate scope and scalability. Furthermore, the method has been successfully applied to the synthesis of omeprazole sulfide and rabeprazole sulfide without the need for TBAB catalysis. A comprehensive green chemistry metrics analysis indicated that this method is much more efficient and greener than the reported synthesis of rabeprazole sulfide.
- Wang, Dong,Liu, Zhenlin,Wang, Zhentao,Ma, Xinyue,Yu, Peng
-
p. 157 - 163
(2019/01/11)
-
- Synthesizing method of 2-pyridine methyl sulfide and synthesizing process of related drugs
-
The invention relates to a simple synthesizing method of 2-pyridine methyl sulfide and related drugs. The method is characterized in that 2-methyl pyridine n-oxide is used as the raw material and pyridine n-oxide or dichloromethane is used as the solvent to have reaction with trifluoroacetic anhydride to obtain a trifluoroacetate intermediate, purification is not needed, the trifluoroacetate intermediate is allowed to have reaction with thiophenol under the catalysis of lithium bromide or tetrabutyl ammonium bromide and by using toluene or ethyl acetate as the solvent to generate the 2-pyridine methyl sulfide. The method is simple to operate, cheap in reagents, easy in reagent obtaining, mild in reaction conditions, wide in substrate applicability, good in position selectivity, high in yield and the like. In addition, the method is successfully applied to the synthesizing of omeprazole sulfide and rabeprazole sulfide, and the synthesizing method does not need catalysts.
- -
-
Paragraph 0122-0124
(2019/01/23)
-
- Rabeprazole correlate D synthetic method
-
The present invention relates to a rabeprazole correlate D synthesis method, which comprises that: (1) in the presence of an excess oxidizing agent, a thioether compound 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridyl]methyl]thio]benzimidazole is oxidized to produce an oxide C; and (2) in the presence of an acid and a reducing agent, the oxide C formed in the step (1) is reduced so as to form the rabeprazole correlate D.
- -
-
Paragraph 0025; 0033-0037
(2018/12/13)
-
- INHIBITORS OF SARM1 NADase ACTIVITY AND USES THEREOF
-
The present disclosure provides compounds useful as inhibitors of SARM1 NADase activity, compositions thereof, and methods of using the same. The present disclosure provides compounds useful for treating a neurodegenerative or neurological disease or disorder, compositions thereof, and methods of using the same.
- -
-
Page/Page column 123
(2018/04/20)
-
- Preparation method for key intermediate rabeprazole thioether
-
The invention discloses a preparation method for rabeprazole thioether 2-[[[4-(3- methoxypropoxy)-3-methylpyridin-2-yl] methyl] sulfo]-1H-benzimidazole. By using Mitsunobu reaction, the rabeprazole thioether is prepared from rabeprazole oxhydryl in one-step synthesis way without chlorination reaction. In the reaction process, the high-corrosive chloride agent, such as, thionyl chloride, is not used, so that the violent corrosion of the reaction to the device is obviously reduced, and meanwhile, the reaction yield is obviously increased due to the shortened reaction step. According to the invention, the process is simple, the reaction condition is mild, the corrosion to the device is small, the yield is higher (70%-80%) and the method is suitable for industrial production.
- -
-
Paragraph 0020-0021
(2017/07/12)
-
- An electronic circular dichroism study for the structurechiroptical relationship of chiral proton pump inhibitors
-
In this paper, we investigated the electronic circular dichroism (ECD) of proton pump inhibitors (PPIs) using a method of combining experimental spectrum and time-dependent density functional theory (TD-DFT) calculations. In our research, an intriguing helicity-like phenomenon was discovered for the relationship between static dipole moment and ECD curves of different conformers in lansoprazole. The scope and validity of the precious phenomenon have been examined by four PPIs using the same method. Hence, it can be used as a reference to determine and verify the absolute configuration of PPIs-type and PPIs-like chiral sulfoxide.
- Zhou, Zhixu,Li, Linwei,Yan, Ning,Du, Lei,Sun, Changshan,Sun, Tiemin
-
supporting information
p. 110 - 112
(2016/03/01)
-
- Rabeprazole sodium crystal method for the preparation of compounds
-
The invention relates to the field of medicine production and in particular relates to a preparation method of a rabeprazole sodium crystal type compound. The preparation method of the rabeprazole sodium crystal type compound comprises the following steps of: by taking 2-mercapto benzimidazole and 2-chloromethyl-3-methyl-4-methoxy propoxy pyridine hydrochloride as raw materials and carrying out a condensation reaction to prepare rabeprazole thioether, and subsequently carrying out an oxidation reaction via the rabeprazole thioether and carrying out salt forming reaction via rabeprazole and sodium hydroxide to acquire the rabeprazole sodium. According to the preparation method of the rabeprazole sodium crystal type compound, the raw materials are low in cost and easy to purchase; samples are basically invariant in related substances and contents under the condition with high temperature and high humidity; the articles are stable in property and low in overall manufacturing cost; and the preparation method of the rabeprazole sodium crystal type compound has the advantages of strictly controlling the temperatures in the steps, being less in by-products, high in yield and non-toxic, and also has the advantages of being short in production period and further improving the production efficiency.
- -
-
Paragraph 0026-0029
(2017/05/06)
-
- PROCESS FOR THE PREPARATION OF RABEPRAZOLE
-
The present invention provides a compound of Formula III, process of its preparation and its use as a reference marker or as a reference standard. The present invention further provides a process for the preparation of rabeprazole, a salt or a solvate thereof. The invention also provides a chromatographic method for testing the purity of rabeprazole, a salt or a solvate thereof.
- -
-
-
- Application of continuous flow micromixing reactor technology for synthesis of benzimidazole drugs
-
Synthesis of pharmaceutically active compounds by employing continuous flow micromixing reactor technology is an interesting research area. In this article we describe the synthesis of benzimidazole core drugs, such as lansoprazole (1a), pantaprazole (1b), and rabeprazole (1c) by using a continuous flow micromixing reactor technology. A key feature of the sulfoxidation includes the decreasing the reaction time from 3 h to ～1 s to minimize the formation of sulfone impurities and improve the yields.
- Reddy, Gunupati Sharathchandra,Reddy, Narra Santosh,Manudhane, Kushal,Rama Krishna, Medisetti Venkata,Ramachandra, Kopparapu Janardana Sarma,Gangula, Srinivas
-
p. 1272 - 1276
(2013/11/06)
-
- Synthesis of metabolites and related substances of rabeprazole, an anti-ulcerative drug
-
Rabeprazole sodium (Aciphex) is a gastric proton pump inhibitor used for the prevention and treatment of gastric acid-related diseases. During the synthesis of bulk drug of rabeprazole sodium, we have observed metabolites rabeprazole sulfide and rabeprazole sulfone and related substances rabeprazole-N-oxide, rabeprazole sulfone-N-oxide, N-aralkyl rabeprazole, chloro rabeprazole, and methoxy rabeprazole as impurities in the drug substance. The present work describes the synthesis and characterization of these compounds. Copyright Taylor & Francis Group, LLC.
- Reddy, Ganta Madhusudhan,Mukkanti, Kaga,Bhaskar, Boluggodu Vijaya,Reddy, Padi Pratap
-
experimental part
p. 278 - 290
(2009/04/11)
-
- An improved process for the production of rabeprazole sodium substantially free from the impurities
-
The present work details the journey towards development of a simple and cost-viable process for large-scale synthesis of rabeprazole sodium substantially free from the impurities. The detailed study of different parameters affecting the quality and yield percentage of the compound has been presented. Yield is increased from 40% (reported process) to 75% with the improved process at sulfoxidation stage.
- Reddy, Pingili Ramchandra,Himabindu, Vurimidi,Jaydeepkumar, Lilakar,Reddy, Ganta Madhusudhan,Kumar, Jonnalagadda Vijaya,Reddy, Ghanta Mahesh
-
scheme or table
p. 896 - 899
(2010/04/22)
-
- PROCESS FOR PREPARATION OF PYRIDINYLMETHYLSULPHINYL BENZIMIDAZOLE COMPOUNDS AND PYRIDINE INTERMEDIATES
-
Process for preparing 4-chloro-substituted pyridine intermediates of Formula (I), useful for preparation of pyridinylmethylsulphinyl benzimidazole compounds, especially Rabeprazole is disclosed herein. The invention, further describes process for preparation of stable Rabeprazole sodium of high purity in a reproducible and consistent manner.
- -
-
Page/Page column 14
(2009/10/22)
-
- A PROCESS FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES AND THEIR SALTS
-
The present relates to a process for the preparation of 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazole derivatives and their pharmaceutically acceptable salts substantially free from their sulfide and the sulfone impurities.
- -
-
Page/Page column 30
(2008/06/13)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF PANTOPRAZOLE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
-
The present invention related to an improved process for the preparation of Pantoprazole sodium sesquihydrate comprising the reaction of 5-difluoromethoxy-2-mercapto benzimidazole with 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride in an aqueous alkali, which upon oxidation with sodium hypochlorite having pH of about 8.5-9.0 and assay of about 3.0-3.5 in chloro solvent followed by reaction with sodium hydroxide in acetone. The invention also relates to the process for the preparation of pantoprazole sodium sesquihydrate form-I.
- -
-
Page/Page column 18
(2008/06/13)
-
- SALTS OF BENZIMIDAZOLE DERIVATIVE WITH AMINES AND PROCESS FOR PRODUCTION THEREOF
-
It is an object of the present invention to provide (1) a process for manufacturing alkali metal salts of 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1 H -benzimidazole which are useful as gastric acid secretion inhibitors, anti-ulcer agents and other drugs and (2) salts of 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1 H -benzimidazole with amines which are intermediates for the production of the alkali metal salts, and a process for manufacturing the same. According to the present invention, disclosed are salts represented by the following formula (I): (wherein A + represents an isopropylammonium ion, sec-butylammonium ion or cyclopentylammonium ion).
- -
-
Page/Page column 13; 14
(2008/06/13)
-
- Process for Production of Benzimidazole Derivative Salt Precipitate
-
The present invention provides a process for the production of a 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1 H-benzimidazole alkali metal salt (1), which is a drug or an intermediate for the production of a drug, the process not requiring large-scale equipment and being excellent in terms of workability, operability and energy conservation. According to the present invention, there is disclosed a process for the production of a salt precipitate represented by formula (1) (wherein B represents an alkali metal ion), the process comprising the steps of: dissolving the compound represented by formula (2) in a first organic solvent and adding an alkali metal hydroxide, or dissolving the alkali metal hydroxide in the first organic solvent and adding the compound represented by formula (2); and further adding a second organic solvent to a reaction mixture obtained.
- -
-
Page/Page column 2-3; 5-6
(2008/06/13)
-
- NEW PROCESS FOR SYNTHESIS OF PROTON PUMP INHIBITORS
-
A process for preparation of rabeprazole sodium comprising oxidation of wet or dry rabeprazole sulphide with sodium hypohalite in water or a mixture of water and water miscible solvent using alkali metal hydroxide and catalyst is disclosed herein. The present invention also discloses process for preparation of rabeprazole sulphide.
- -
-
Page/Page column 8
(2008/06/13)
-
- Synthetic studies connected with the preparation of H+/K +-ATPase inhibitors rabeprazole and lansoprazole
-
Synthesis of lansoprazole and rabeprazole using common intermediates is devised. The common intermediates, 2-[(4-nitro-3-methylpyridin-2-yl) methanesulfanyl]-1H-benzoimidazole and 2-[(4-chloro-3-methyl-pyridin-2-yl) methanesulfanyl]-1H-benzoimidazole, were prepared in several ways.
- Radl, Stanislav,Klecan, Ondrej,Havlicek, Jaroslav
-
p. 1447 - 1453
(2007/10/03)
-
- Crystalline form Z of rabeprazole sodium and process for preparation thereof
-
The present invention relates to novel crystalline Form Z of rabeprazole sodium and a process for the preparation of the crystalline Form Z as well as composition, pharmaceutical composition and method utilizing the crystalline Form Z.
- -
-
-
- Crystalline form Z of rabeprazole sodium and process for preparation thereof
-
The present invention relates to novel crystalline Form Z of rabeprazole sodium and a process for the preparation of the crystalline Form Z as well as composition, pharmaceutical composition and method utilizing the crystalline Form Z.
- -
-
Page/Page column 6
(2008/06/13)
-
- PYRIDINE DERIVATIVES HAVING ANTI-ULCERATIVE ACTIVITY
-
Pyridine derivatives useful for preventing or treating peptic ulcers, pharmaceutical preparations and methods of treating peptic ulcers are described.
- -
-
-
