cas 102625-70-7, Pantoprazole | Articles data

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Preparation of Pantoprazole sodium method and Pantoprazole sodium (by machine translation)
The invention relates to the preparation of Pantoprazole sodium method and pantoprazole sodium. In particular, the invention relates to a method of preparing pantoprazole sodium, comprising the following steps: 1) to 2 - hydroxymethyl - 3, 4 - dimethoxy pyridine (II) as the starting material, in under the action of chloride, the compound of formula III; 2) will be of the formula III compound in the presence of an inorganic base with 5 - difluoro - 2 - mercapto - 1 H - benzimidazole condensation, the compound of formula IV; 3) will be of the formula IV compound is oxidized by an oxidant generating 5 - difluoro - 2 - [(3, 4 - dimethoxy - 2 - pyridyl) methyl] sulfinyl - 1 H - benzimidazole is pantoprazole; 4) the obtained 5 - difluoro - 2 - [(3, 4 - dimethoxy - 2 - pyridyl) methyl] sulfinyl - 1 H - benzimidazole with sodium hydroxide reaction to produce salt that pantoprazole sodium (I); and optionally a 5) the resulting pantoprazole sodium is refined. The method of the invention said product has high purity, and the related impurities such as oxidation impurity, reducing the impurity, decomposition low impurity content. (by machine translation)
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(2019/02/27)

Triple Mode of Alkylation with Ethyl Bromodifluoroacetate: N, or O-Difluoromethylation, N-Ethylation and S-(ethoxycarbonyl)difluoromethylation
In this report, we have explored a triple mode of chemical reactivity of ethyl bromodifluoroacetate. Typically, bromodifluoroacetic acid has been used as a difluorocarbene precursor for difluoromethylation of soft nucleophiles. Here we have disclosed nucleophilicity and base dependent divergent chemical reactivity of ethyl bromodifluoroacetate. It furnishes lithium hydroxide and cesium carbonate promoted difluoromethylation of tosyl-protected aniline and electron-deficient phenols respectively. Interestingly, switching the base from lithium hydroxide to 4-N,N-dimethylamino pyridine (DMAP) tosyl-protected anilines afforded the corresponding N-ethylation product. Whereas, highly nucleophilic thiophenols furnished the corresponding S-carboethoxydifluoromethylation product via a rapid SN2 attack to the bromine atom prior to the ester hydrolysis. This mechanistic divergence was established through several control experiments. It was revealed that difluoromethylation reaction proceeds through a tandem in situ ester hydrolysis/decarboxylative-debrominative difluorocarbene formation and subsequent trapping by the soft nucleophile-NHTs or electron-deficient phenolic ?OH groups. In the presence of DMAP the hydrolysis of the ester is perturbed instead a nucleophilic attack at the ethyl moiety provides the N-ethylation product. Hence, besides the development of a practical base-promoted N-difluoromethylation of amines and electron-deficient phenols, divergent reactivity pattern of inexpensive and user-friendly ethyl bromodifluoroacetate has been explored. (Figure presented.).
Polley, Arghya,Bairy, Gurupada,Das, Pritha,Jana, Ranjan
p. 4161 - 4167
(2018/09/21)

Method for preparing benzimidazole proton pump inhibitor
The invention provides a novel method for preparing a benzimidazole proton pump inhibitor, and belongs to the field of medicine synthesis. According to the method provided by the invention, a complexformed by using graphene oxide and a transition metal salt is used as a catalyst, and the corresponding benzimidazole proton pump inhibitor is obtained through oxidizing a thioether by an oxidizing agent under an alkaline condition in an organic solvent. The method has the advantages of mild reaction condition, high yield, environmental friendliness, and less impurity, the catalyst can be recycled, and the method is suitable for industrial production.
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Paragraph 0018; 0019; 0020; 0021; 0022; 0023; 0024-0041

(2018/09/08)

Method for preparing high-purity razole intermediate and medicine by using green technology instead of phosgene, thionyl chloride and other toxic and harmful substances
The invention discloses a method for preparing a high-purity razole intermediate and a medicine by using a green technology instead of phosgene, thionyl chloride and other toxic and harmful substances. The preparation method comprises the following steps: dissolving Ph3PO in an organic solvent, placing the obtained solution in a reaction bottle, dropwise adding BTC to form a high-efficiency chloration reagent, carrying out a heat insulation reaction for a period of time after the dropwise addition is finished, dissolving a razole hydroxide in the organic solvent, dropwise adding the obtained solution to the above system, carrying out a heat insulation reaction for a period of time, carrying out suction filtration, and drying the obtained dried reaction product to obtain razole chloride. In the process, the Ph3PO is equivalently regenerated, a mother liquor part is concentrated to precipitate the Ph3PO at a low temperature, and the Ph3PO can be repeatedly used after being washed with a solvent with small polarity. The method has the advantages of few side reactions, high product quality, few "three wastes" pollutions, high atomic economy, and good promotion and application prospect. The invention also provides a relevant razole medicine prepared from the razole chloride obtained through the green technology. The medicine has obviously higher purity than medicines obtained through traditional methods.
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(2017/09/01)

Preparation method for S-pantoprazole sodium
The invention discloses a preparation method for S-pantoprazole sodium. The method comprises the following steps: performing oxidation and substitution reaction on a compound as shown in formula VII; adding soybean peptide hydrolase for hydrolyzing and resolving; adding sodium hydroxide into the hydrolysis product for salifying, and then performing extraction separation, thereby acquiring (-)S-enantiomer; and performing basic hydrolysis, acidifying crystallization and salifying, thereby acquiring pantoprazole sodium. According to the method, the soybean peptide hydrolase is taken as a chiral resolution reagent, the process is simple, the reaction conditions are mild, the method is environment-friendly, the purity of the acquired S-pantoprazole sodium and the chiral purity both can reach above 99.9%, and the preparation method is suitable for industrial production.
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Paragraph 0022; 0053; 0054; 0060; 0061; 0067; 0068

(2017/04/13)

Process for preparing 2-sulfinyl-1H-benzimidazoles
The present invention relates to a process for preparing 2-(2-pyridinylmethylsulfinyl)-1H-benzimidazoles by oxidizing a thioether precursor in the presence of trifluoroethanol.
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Page/Page column 11

(2009/04/23)

Method for preparing 2- (2-pyridinylmethylsulfinyl) benzimidazoles
The present invention provides a method for preparing an antiulcer agent, 2-(2-pyridinylmethylsulfinyl)benzimidazoles, such as Omeprazole, Lansoprazole, Pantoprazole and Rabeprazole, which includes oxidizing an intermediate having a linkage of methylthio group (—CH2S—) to methylsulfinyl (—CH2S(O)—) in the presence of an oxidation catalyst of an alkali metal salt of tungstate at a temperature of 10-50° C.
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Page/Page column 3

(2009/01/24)

PROCESS FOR PREPARING PANTOPRAZOLE SODIUM SESQUIHYDRATE
Disclosed herein is a process for preparation of pantoprazole sodium sesquihydrate represented by Formula 1 from pantoprazole as a starting material.
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Page/Page column 4-5

(2009/07/17)

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.
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Page/Page column 16

(2009/10/22)

PROCESS FOR THE PREPARATION OP PANTOPRAZOLE SODIUM AND PANTOPRAZOLE SODIUM SESQUIHYDRATE
The present invention relates to a process for the preparation of pantoprazol sodium sesquihydrate of formula (I) and pantoprazole sodium.
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Page/Page column 11

(2009/03/07)

SELECTIVE PRODUCTION OF SULPHOXIDES
The invention pertains to a process for producing a sulphoxide compound, comprising oxidizing a thioether compound with an ozonide formed from a olefin and ozone, to obtain the corresponding sulphoxide compound, provided that the olefin is not ethene. The ozonide converts thio - ether compounds selectively, unlike its art - known oxidizing counterparts. The milder ozonide does not require manipulation of the stoichiometric amount of available oxidizing agent during the reaction, to prevent the formation of sulphones.
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Page/Page column 12

(2009/03/07)

Solid Crystalline Form of Pantoprazole Free Acid, Salts Derived Therefrom and Process for Their Preparation
The invention relates, in general, to a new solid crystalline form of pantoprazole free acid (denominated “Form III”), salts derived therefrom (e.g., pantoprazole sodium and pantoprazole sodium sesquihydrate) and methods for producing the same. The invention further includes formulating pantoprazole free acid Form III, salts derived therefrom (e.g., pantoprazole sodium and pantoprazole sodium sesquihydrate) and/or in vivo cleavable prodrugs thereof (collectively “the compounds of the invention”) into readily usable dosage units for the therapeutic treatment (including prophylactic treatment) of mammals, including humans.
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Page/Page column 1; 3-4

(2008/12/04)

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.
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Page/Page column 26-27

(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.
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Page/Page column 17-20

(2008/06/13)

PROCESS FOR THE PREPARATION OF PYRIDINE COMPOUNDS
A process for preparation of a compound of formula (I), both as the isomeric mixture and individual isomers, wherein Q is ═CR8— or ═N—; each R1, R2, R3, R4 is independently selected from hydrogen, halogen, hydroxy; nitro; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen or C1-C6 alkoxy; phenyl-C1-C6 alkyl; phenyl-C1-C6 alkoxy; and —N(RaRb) wherein each Ra and Rb is independently hydrogen or C1-C6 alkyl or Ra and Rb, taken together with the nitrogen atom they are linked to, form a saturated heterocyclic ring; and each R5, R6, R7, R8 is independently selected from hydrogen, halogen, hydroxy; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen; C1-C6 alkyl-carbonyl, C1-C6 alkoxy-carbonyl, and oxazol-2-yl; comprising converting a compound of formula (IV), to said compound of formula (I), in the presence of a catalyst, if necessary in an organic solvent.
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Page/Page column 4

(2008/06/13)

A process for the preparation of pyridine compounds
A process for the preparation of a compound of formula (I) or a salt thereof, both as the isomeric mixture and the individual isomers, wherein Q is =CR8- or =N-; each R1, R2, R3 and R4 is independently selected from hydrogen, halogen, hydroxy; nitro; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen or C1-C6 alkoxy; phenyl-C1-C6 alkyl; phenyl-C1-C6 alkoxy; and - N(RaRb) wherein each Ra and Rb is independently hydrogen or C1-C6 alkyl or Ra and Rb, taken together with the nitrogen atom they are linked to, form a saturated heterocyclic ring; and each R5, R6, R7 and R8 is independently selected from hydrogen, halogen, hydroxy; C1-C6 alkyl optionally substituted with hydroxy; alkylthio C1-C6; C1-C6 alkoxy optionally substituted with halogen; C1-C6 alkyl-carbonyl, C1-C6 alkoxy-carbonyl, and oxazol-2-yl; comprising converting a compound of formula (IV), or a salt thereof, wherein Q, R1, R2, R3, R4, R5, R6 and R7 are as defined above, to said compound of formula (I), or a salt thereof, in the presence of a catalyst, if necessary in an organic solvent; and, if desired, converting a compound of formula (I) to a salt thereof to another compound of formula (I); and/or, if desired, resolving an isomeric mixture of a compound of formula (I) in the individual isomers.
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Page/Page column 6

(2008/06/13)

PROCESS FOR THE MANUFACTURE OF ANTIULCERATIVES
The present invention relates to an improved process for the preparation of antiulcerative compounds, e.g., Pantoprazole, Lansoprazole, Omeprazole and Rabeprazole etc. The process provides a method for preparing 2-(2-pyridylmethyl-sulfinyl)benzimidazole compounds by subjecting 2-(2-pyridylmethyl-thio)benzimidazole compounds to oxidation with sodium hypochlori solution in presence of an alkali.
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Page/Page column 6

(2008/06/13)

PROCESS FOR THE PREPARATION OF 2-(2-PYRIDYLMETHYL)-SULFINYL-1H-BENZIMIDAZOLES
The present invention relates to an improved process for the preparation of substituted. 2-(2-pyridylmethyl)-sulfinyl-1H-benzimidazoles or its derivatives, which are useful for a medicament such as an inhibitor of gastric acid secretion or an anti-ulcer agent or an intermediate to produce medicaments in good yield and high purity. More particularly, the present invention relates to a process for preparing a sulfoxide compound of the formula (I) in good yield and relatively high purity and pharmaceutically acceptable salt, hydrate and solvate thereof. (I) wherein R1 and R3 are selected from the group consisting of hydrogen, methyl or C1-4 alkoxy, R2 is selected from the group consisting of substituted or unsubstituted C1-4 alkoxy, R4 is selected from the group consisting of hydrogen or substituted or unsubstituted C1-4 alkoxy. Comprising the step of oxidizing a sulfide compound of formula (II) with Peroxyacetic acid or its derivatives necessarily at the pH 5-7 using aqueous sodium carbonate solution. (II) wherein R1 R2 R3 and R4 are as defined above.
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Page/Page column 8

(2008/06/13)

A NOVEL ONE POT PROCESS FOR PREPARATION OF PANTOPRAZOLE SODIUM SESQUIHYDRATE
The present invention provides a novel one-pot process for preparation of Pantoprazole sodium sesquihydrate Form-I in the pure form without isolating the pantoprazole base.
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Page/Page column 8-9

(2008/06/13)

PROCESS FOR THE PREPARATION OF PANTOPRAZOLE
The present invention is related to a new process for the preparation of pantoprazole (I) and pharmaceutical acceptable salts thereof, with a good yield and a high purity. In said process, the introduction of the methoxy group is carried over the position 4 of the piridine ring of compound (IV) by substitution of the chlorine atom, by the reaction with an alkaline methoxide in a mixture of methanol and an aprotic polar solvent. Also an aspect of the invention is an isolating process that includes a method for the purification of pantoprazole, and a process for the preparation of compound (IV), which is used as starting product for the preparation of pantoprazole.
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Page/Page column 15

(2008/06/13)

A PREPARATION METHOD FOR SUBSTITUTED 2-(2-PYRIDYLMETHOYLSULPHINYL)-l-H-BENZIMID AZOLES
The invention relates to a process for the preparation of a substituted 2-(2-pyridylmethylsulphinyl)-l-H-benzimidazole involving the reaction of a corresponding 2-(2-pyridylrnethylthio)-l-H-benzirnidazole compound with a hypohalite oxidation agent in the presence of a phase transfer catalyst, wherein the reaction involves a biphasic reaction mixture containing an aqueous and an organic phase. The reaction can immediately succeed the formation of said 2-(2-pyridylmethylthio)-l-H-benzimidazole compound in a one pot synthesis, in order to avoid time-consuming and costly purification steps. Overoxidation, leading to sulphone impurities, is thus avoided and yields improved. Hence, the invention also relates to a substituted 2-(2-pyridylmethylsulphinyl)-l-H-benzimidazole containing less than 0.2 wt% sulphone impurities.
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Page/Page column 13

(2010/11/30)

PROCESS FOR PREPARATIONS AND PURIFICATION OF PANTOPRAZOLE SESQUIHYDRATE
The present invention relates to a method for oxidation of sulfide analog with sodium hypochlorite in methylene chloride, and also an improved process for the purification of pantoprazole sodium sesquihydrate.
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Page/Page column 4; 6-7

(2008/06/13)

METHOD FOR PREPARING 2- (2-PYRIDYLMETHYLSULPHINYL) BENZIMIDAZOLES
The present invention provides a method for preparing an antiulcer agent, 2-(2-pyridylmethylsulphinyl)benzimidazoles, such as Omeprazole, Lansoprazole and Pantoprazole, which includes oxidizing an intermediate having a linkage of methylthio group (—CH2S—) to methylsulfinyl (—CH2S(O)—) in the presence of an oxidation catalyst of acetyl acetonate of molybdenium (II) [(CH3C(O)CH2C(O)CH2)2Mo].
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Page/Page column 3

(2008/06/13)

PYRIDINE BENZIMIDAZOLE SULFOXIDES WITH HIGH PURITY
A method for preparing a pyridine benzimidazole sulfoxide compound having the formula (I) with the step of oxidizing a pyridine benzimidazole thioether compound with an oxidation agent, during that oxidation step a pyridine benzimidazole sulfone compound is formed as an undesired by-product. It is proposed to stop the oxidation step prior the amount of undesired pyridine benzimidazole sulfone product exceeds 1,0 %-by weight based on the entire amounts of compounds.
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Page/Page column 20

(2008/06/13)

PROCESS FOR THE PREPARATION OF PYRIDIN-2-YLMETHYLSULPHINYL-1H-BENZIMIDAZOL COMPOUNDS
The invention relates to a process for preparing mixtures of enantiomers of PPI′s proton pump inhibitors having a sulphinyl structure, i.e. Pyridine-2-ylmethylsulfinyl-1H-benzimidazoles, using a mixture of enantiomers of chiral zirconium complexes or chiral hafnium complexes.
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Page/Page column 5

(2008/06/13)

PROCESS FOR PREPARING 2-[(PYRIDINYL)METHYL]SULFINYL-SUBSTITUTED BENZIMIDAZOLES AND NOVEL CHLORINATED DERIVATIVES OF PANTOPRAZOLE
The present invention provides a process comprising admixing a thioether with about 1.05 to about 1.6 molar equivalents of an active chlorine-containing oxidant, preferably sodium hypochlorite, and about 2.5 to about 5.0 molar equivalents of an alkali metal base; and recovering a sulfoxide that is preferably pantoprazole, lansoprazole, omeprazole, or rabeprazole. The process may further comprise contacting the sulfoxide with a source of sodium ions, preferably sodium hydroxide, to produce the sodium salt of the sulfoxide. The invention also relates to novel chlorinated derivatives of pantoprazole including 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-chloromethyl]sulfinyl]-1H- benzimidazole and 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-chlorohydroxymethyl] sulfinyl]-1H-benzimidazole and processes for making them. The invention also relates to processes of quantifying and identifying a compound other than pantoprazole in a mixture of pantoprazole and at least one other compound.
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Page 20-22

(2008/06/13)

Process for the preparation of pantoprazole and intermediates therefor
A novel process is described for the preparation of the active principle pantoprazole based on the use of novel intermediate compounds of general formula (I) where X is an atom of halogen and n=0 or 1, so that when n=1, the intermediate compounds are methoxylated, and when n=0 said intermediate compounds are first oxidized to n=1 and thereafter are methoxylated. Also described are the novel intermediates, as well as the process for the preparation thereof.
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(2008/06/13)

PROCESS FOR THE PREPARATION OF SULPHINYL DERIVATIVES BY OXIDATION OF THE CORRESPONDING SULFIDES
The present invention relates to a mild and industrially applicable process for preparing sulfinyl derivatives of Formula (II), useful as inhibitors of gastric acid secretion, comprising the selective oxidation of the corresponding sulfides of Formula (I), as represented in scheme (I) and (II) in which said oxidation is performed with hydrogen peroxide in the presence of low amounts of a rhenium compound as catalyst, at a temperature from 0° C to room temperature.
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Page 9

(2008/06/13)

Process for the preparation of organic compounds containing a sulfinyl or sulfonyl group in the presence of epsilon-phthalimidoperhexanoic acid
A process for the oxidation of thioethers to sulfoxides or sulfones or for the oxidation of sulfoxides to sulfones by treatment of thioethers or sulfoxides with an oxidizing amount of ε-phthalimidoperhexanoic acid is particularly useful for the preparation of compounds of industrial interest, in particular pharmaceuticals for human or veterinary use.
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Page 4

(2008/06/13)

Process for the preparation of organic compounds containing a sulfinyl or sulfonyl group
A process for the oxidation of thioethers to sulfoxides or sulfones or for the oxidation of sulfoxides to sulfones by treatment of thioethers or sulfoxides with an oxidizing amount of ε-phthalimidoperhexanoic acid is particularly useful for the preparation of compounds of industrial interest, in particular pharmaceuticals for human or veterinary use.
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Page 3

(2008/06/13)

Processes for the production of substituted 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles
Improved processes for preparing substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles are disclosed.
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Page 4

(2008/06/13)

Substituted 2-(2-methyl Pyridylpyrimidine) sulfinylation -1H-dihydrobenzo aminoalkaneimidazole manufacturing method
Improved processes for preparing substituted 2-(2-pyridylmethyl) sulfinyl- 1H-benzimidazoles are disclosed.
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Page/Page column 11

(2008/06/13)

An improved and single-pot process for the production of pantoprazole substantially free from sulfone impurity
Pantoprazole (1), a substituted benzimidazole derivative, is an irreversible proton pump inhibitor, essentially used for the prevention and treatment of gastric acid-related diseases. The process for its preparation generally suffers from the drawback of producing a potential sulfone impurity (5). The present work details a report of the journey towards the development of a simple, single-pot process for the production of pantoprazole, substantially free from sulfone impurity (5). The detailed study of the different parameters affecting the purity and yield of the compound has been presented.
Mathad, Vijayavitthal T.,Govindan, Shanmugam,Kolla, Naveen Kumar,Maddipatla, Madhavi,Sajja, Eswaraiah,Sundaram, Venkataraman
p. 266 - 270
(2013/09/04)

Processes for the production fo substituted 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles
Improved processes for preparing substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles are disclosed.
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(2008/06/13)

Prodrugs of proton pump inhibitors
Prodrugs of the pyridyl methyl sulfinyl benzimidazole type proton pump inhibitor drugs have a hydrolyzable arylsulfonyl or heteroarylsulfonyl group attached to the benzimidazole nitrogen. The prodrugs of the invention hydrolyze under physiological conditions to provide the proton pump inhibitors with a half life measurable in hours, and are capable of providing sustained plasma concentrations of the proton pump inhibitor drugs for longer time than presently used drugs. The generation of the proton pump inhibitor drugs from the prodrugs of the invention under physiological conditions allows for more effective treatment of several diseases and conditions caused by gastric acid secretion.
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(2008/06/13)

PROCESS FOR SYNTHESIS OF SUBSTITUTED SULPHOXIDES
A novel process for enantioselective synthesis of single enantiomers of omeprazole or its alkaline salts, of other optically pure substituted 2-(2-pyridinylmethyl-sulphinyl) -1H-benzimidazoles as well as of other structurally related sulphoxides or their alkaline salts. The claimed process is an asymmetric oxidation of a pro-chiral sulphide to the single enantiomers or an enantiomerically enriched form of the corresponding sulphoxide. The application also claims the enantiomeric sulphoxide products produced by the process and their use in medicine
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(2008/06/13)

METHOD OF USING (H+/K+)ATPASE INHIBITORS AS ANTIVIRAL AGENTS
A class of compounds which are (H+/K+) ATPase inhibitors can be used for the treatment of viral infections. Compounds of particular interest are defined by Formula III: wherein D is N or CH; wherein R7 is one or more radicals selected from hydrido, alkoxy, amino, cyano, nitro, hydroxyl, alkyl, halo, haloalkyl, carboxyl, alkanoyl, nitro, amino, alkylamino, aminocarbonyl , aminosulfonyl , alkylaminocarbonyl, alkylcarbonylamino, alkoxycarbonyl, alkylaminosulfonyl, alkylsulfonylamino, alkylthio, alkyl-sulfinyl and alkylsulfonyl; wherein R8 is selected from hydrido, alkyl and cycloalkyl; wherein R9 is one or more radicals selected from hydrido, alkoxy, amino, alkyl, halo, cyano, nitro, hydroxyl, haloalkyl, nitro, carboxyl, alkanoyl, amino, alkylamino, dialkylamino, aminocarbonyl , alkylaminocarbonyl, alkylcarbonylamino, aminosulfonyl, alkylaminosulfonyl, alkylsulfonylamino, alkoxycarbonyl, alkylthio, alkylsulfinyl and alkylsulfonyl; and wherein R10 and R11 are independently selected from hydrido, alkyl, aryl, alkylcarbonyl and arylcarbonyl wherein the aryl ring may be further substituted with one or more radicals selected from alkyl, halo, hydrazidylcarbonyl, aminocarbonyl and alkoxy; or wherein R10 and R11 together with the nitrogen atom form a heterocyclic ring
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(2008/06/13)

Crystals of benzimidazole derivatives and their production
A substantially solvent-free and stable crystal of the compound of the formula: STR1 wherein the ring A may optionally be substituted, R1 represents hydrogen or an N-protecting group, each of R2, R3 and R4 (1) a hydrogen atom, (2) an alkyl group which may optionally be substituted with halogen atom(s) or (3) an alkoxy group which may optionally be substituted with halogen atom(s) or alkoxy; or its salt, is produced by subjecting a solvate of the compound (I) or its salt to de-solvent treatment, in an industrially advantageous method.
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(2008/06/13)

(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate
[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.
Kohl,Sturm,Senn-Bilfinger,Simon,Kruger,Schaefer,Rainer,Figala,Klemm
p. 1049 - 1057
(2007/10/02)