- Preparation method of funolasan fumarate
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The present invention provides a method for preparing funorasine fumarate, comprising the following steps: (1) the compound of formula I is azidine to give a compound of formula II.; (2) the compound of formula II. is cyclized with the compound of formula III. to give a compound of formula IV.; (3) the compound of formula IV. is condensed with a compound of formula VI. to give a compound of formula VII. compound; (4) a compound of formula VII. is deprotected with acid to obtain a vonorasin free base; (5) a vonorasin free base is salted with fumarate to give vonorasin fumarate. According to the method of the present invention to synthesize vonoracin fumarate, compared with the prior art, the total yield of vonora fumarate increased to more than 60%, and the yield has been greatly improved. Furthermore, compound formula IV. can be used as a new intermediate for the preparation of funolasine fumarate.
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- Preparation method of tenosynol fumarate
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The invention discloses a preparation method of fumarate administered by a synthetic digestive system. In particular, the invention relates to a method for large-scale preparation of tenoteno fumarate; the adopted starting materials are easy to obtain; th
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Paragraph 0039-0040
(2021/11/19)
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- Vonoprazan fumarate intermediate and preparation method thereof
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The invention provides a vonoprazan fumarate intermediate compound as well as a preparation method and application thereof. Compared with the prior art, the technical scheme provided by the invention avoids the hydrogenation reaction operation with higher
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- Preparation method of high-purity vonoprazan fumarate
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The invention discloses a preparation method of high-purity vonoprazan fumarate. The preparation method comprises the steps of 1, preparing 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl) pyrrole-3-formaldehyde; 2, dissolving the 5-(2-fluorophenyl)-1-(pyridine
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Paragraph 0054
(2021/05/26)
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- Preparation method of high purity funolasine fumarate
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The present invention discloses a method for preparing a pure vonorasine fumarate, comprising the following steps: 5- (2-fluorophenyl)-1 [(pyridin-3-yl) sulfonyl] -1H- pyrrole-3-formaldehyde as the starting material, the starting material is dissolved in
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Paragraph 0071-0078
(2022/01/08)
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- Vonoprazan fumarate preparation method
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The invention provides a vonoprazan fumarate preparation method, which comprises: reducing 5-(2-fluorophenyl)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-formaldehyde with a reducing agent, adding oxalic acid, carrying out a reaction to prepare a crude vonopra
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- Preparation method of vonoprazan fumarate
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The invention provides a preparation method of vonoprazan fumarate (I). The method comprises the following steps: selecting easily-available 5-(2-fluorophenyl)-1-(3-pyridylsulfonyl)-3-cyano-1H-pyrrole(II) as a raw material, carrying out a reaction in one
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Paragraph 0038-0051
(2019/11/25)
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- Preparation method of low-impurity Vonoprazan fumarate
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The invention provides a preparation method of low-impurity Vonoprazan fumarate. A method for removing impurities A-E during preparation of Vonoprazan comprises the steps: preparing Vonoprazan hydrobromide from Vonorazan, and removing the impurities A-E which are difficult to remove by using a recrystallization purifying method, wherein the method for removing the impurities A-E during preparationof Vonoprazan has good selectivity to the impurities A-E. The preparation method of low-impurity Vonoprazan fumarate comprises the steps: performing a reaction on 5-(2-fluorophenyl)-1-(pyridyl-3-ylsulfonyl)-1H-pyrrole-3-formaldehyde and methylamine or a salt of methylamine, then performing reduction so as to obtain Vonoprazan, then preparing Vonoprazan hydrobromide, then performing salt dissociation so as to obtain Vonoprazan free alkali, preparing Vonoprazan fumarate with a purity of 99.7% or above, and then performing recrystallization refining so as to obtain Vonoprazan fumarate with a purity of 99.9% or above. The invention provides an impurity D, a preparation method of the impurity D and application of the impurity D as an impurity reference substance in Vonoprazan fumarate.
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- An Efficient, Scalable and Eco-friendly Synthesis of 4,5-substituted Pyrrole-3-Carbonitriles by Intramolecular Annulation on Pd/C and HZSM-5
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An efficient and eco-friendly protocol for the synthesis of diverse 4,5-substituted 1H-pyrrole-3-carbonitriles has been developed using commercially available HZSM-5 and Pd/C as recyclable heterogeneous catalysts with more excellent yields (up to 98 %) than traditional liquids acids, and successfully applied in the practical synthesis of vonoprazan. The conspicuous features of this protocol are higher product yield, easy work-up, eco-friendly and reusability of catalysts.
- Chen, Jianchao,Li, Chengtao,Zhou, Yanan,Sun, Changshan,Sun, Tiemin
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p. 1943 - 1948
(2019/03/26)
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- New preparation method of Vonoprazan
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The invention discloses an improved preparation method of Vonoprazan, and particularly discloses a preparation method of a compound Vonoprazan with a structure shown in the description. According to the method, a compound 5-(2-fluorophenyl)-1H-pyrrole-3-carboxylic ester is taken as a raw material and subjected to amination with water as a solvent, a product is reduced, and Vonoprazan is prepared.The technology adopts short steps, and is low in cost, environmentally friendly and suitable for large-scale industrial production.
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- The amide compound and the compound preparation fumaric acid fertile norah approves of the method (by machine translation)
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The invention discloses a amide compound and this compound preparation fumaric acid fertile norah approves of the method, the amide compound of formula (5) shown compound, can be used for preparing fumaric acid fertile norah approves. The beneficial effec
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Paragraph 0150-0152; 0157; 0161; 0165; 0170; 0174; 0178
(2018/07/15)
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- The preparation method of the fumaric acid fertile norah approves
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The invention relates to the field of drug preparation researches, and especially relates to a preparation method of 1-[5-(2-fluorophenyl)-1-(pyridyl-3-ylsulfonyl)-1H-pyrryl-3-yl]-N-methyl methylamine fumarate (represented by formula I) and an intermediate thereof. The method is characterized in that the above compound represented by formula (I) is prepared through nitrogen monomethylation and salt formation with a compound represented by formula (V) as an important intermediate. The structural formula of the compound represented by formula (V) is shown in the specification, and the structural formula of the compound represented by formula (I) is also shown in the specification.
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- Preparation method of vonoprazan fumarate
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The invention relates to a preparation method of vonoprazan fumarate, belonging to the technical field of preparation of a raw material medicine. The preparation method of the vonoprazan fumarate comprises the following steps: 5-(2-fluorophenyl)-1H-pyrrole-3-carbonitrile is used as a starting material to react with pyridine-3-sulfonyl chloride to form 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-nitrile; the 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-nitrile is reduced to prepare 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-formaldehyde; then vonoprazan is prepared; and then a salt formation step is used to prepare the vonoprazan fumarate. The preparation method is suitable for industrial production.
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- METHOD FOR PRODUCING PYRROLE COMPOUND
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The present invention provides a production method of a 3-cyanopyrrole compound possibly useful as an intermediate for pharmaceutical products. A production method of compound (II) including subjecting compound (I) to a reduction reaction, in which the af
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- Vonoprazan salts and crystal forms, and preparation method and application thereof
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The invention relates to vonoprazan dihydrochloride, vonoprazan dihydrobromide, vonoprazan disulfate, vonoprazan nitrate, vonoprazan diphosphate, vonoprazan sulfonate, vonoprazan 1,4-hemibutanedisulfonate, vonoprazan 1,4-butanedisulfonate, vonoprazan 2-is
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Paragraph 0475; 0476
(2018/03/24)
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- Synthetic process for Vonoprazan fumarate
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The invention provides a preparation method for preparing high-purity 5-(2-fluorophenyl)-N-methyl-1-(3-pyridine sulfonyl)-1H-pyrrole-3-methylamine fumarate. The method comprises the following steps: taking 5-(2-fluorophenyl)-N-methyl-1-(3-pyridine sulfony
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Paragraph 0057; 0060; 0062-0064; 0066-0077; 0078-0085
(2018/03/24)
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- The preparation method of the fumaric acid fertile norah approves
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The invention discloses a preparation method of Vonoprazan fumarate. The preparation method comprises steps as follows: 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3- formaldehyde is dissolved in a solvent, methylamine gas is introduced at the t
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Paragraph 0026-0055
(2018/07/15)
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- Purification method of vonoprazan fumarate
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The invention discloses a purification method of vonoprazan fumarate. The purification method of the vonoprazan fumarate I, provided by the invention, comprises the following steps: forming a solutionby a vonoprazan fumarate I crude product and an organic
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Paragraph 0038-0040
(2018/04/02)
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- Novel and practical synthesis of vonoprazan fumarate
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A novel and practical strategy for the synthesis of vonoprazan fumarate 1, a novel potassium-competitive acid blocker, has been developed. Vonoprazan fumarate was obtained through a four-step process starting from 5-(2-fluorophenyl)-1H-pyrrole-3-carboxylate and including ester hydrolyzing, methylamine substitution, sulfonyl chloride substitution, and amide reduction. Key to the strategy is the amide reduction taking a novel and practical protocol. The main advantages of this route include two parts: controllable impurity and acceptable overall yield.
- Yu, Qian-Ying,Zeng, Huang,Yao, Kai,Li, Jian-Qi,Liu, Yu
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p. 1169 - 1174
(2017/06/09)
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- Fumaric acid fertile norah approves of the preparation process
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The invention relates to a preparation technology for vonoprazan fumarate. The preparation method comprises: reacting 2'-fluoroacetophenone (II) with ammonium acetate to generate 1-(2-fluorophenyl)ethen-1-amine (III), then reacting with 2-bromopropanal for cyclization for generating 2-(2-fluorophenyl)-4-methyl-1H-pyrrole (IV), reacting the compound IV with 3-pyridinesulfonyl chloride to generate 5-(2-fluorophenyl)-3-methyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole (V), then performing N-bromosuccinimide substitution to generate 5-(2-fluorophenyl)-3-bromomethyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole (VI), and finally performing methylamination reaction and salt forming, so as to obtain vonoprazan fumarate. The method avoids usage of a toxic reagent liquid bromine and hydrogen chloride gas capable of corroding equipment in the prior art, possesses the advantages of simple technological route, mild reaction conditions, controllable operation, environment friendliness and high product yield, and is suitable for large-scale industrialized production.
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- A preparation method of the fumaric acid fertile norah approves
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The invention discloses a preparation method of vonoprazan fumarate. The preparation method includes: S1, dissolving 5-(2-fluorophenyl)-1H-pyrrole-3-carboxaldehyde (I) in organic solvent, mixing with methylamine alcohol solution for 6-8h to generate imine
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- Vonoprazan fumarate preparation method
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The invention concretely relates to a vonoprazan fumarate preparation method, and belongs to the field of medicines and chemical engineering. The method comprises the following steps: 1, carrying out condensation on 2-fluoroacetophenone used as an initial raw material and allylamine to obtain a compound IV; 2, carrying out a ring closing reaction on the compound IV under the catalysis of a copper catalyst in the presence of a ligand in order to obtain a compound V; 3, carrying out a sulfoamidation reaction on the compound V and pyridine-3-sulfonyl chloride to generate a compound VII; 4, carrying out a bromination reaction on the compound VII by using N-bromosuccimide in order to generate a compound VIII; 5, carrying out an amination reaction on the compound VIII and methylamine hydrochloride under the action of a catalyst and an alkali in order to obtain vonoprazan alkali; and 6, carrying out salt formation on the vonoprazan alkali and fumaric acid in order to obtain vonoprazan fumarate. The preparation method has the advantages of simplicity in operation, mild reaction conditions, high yield and high purity of the product, and easiness in industrial production.
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- Preparation method of vonoprazan fumarate
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The invention provides a preparation method of vonoprazan fumarate. The preparation method comprises the following steps of enabling 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1-H-pyrrole-3-formaldehyde and methylamine to react to generate Schiff base; us
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- Vonoprazan fumarate single crystal, preparation method and uses thereof
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The present invention relates to a vonoprazan fumarate single crystal, a preparation method and uses thereof. According to the present invention, the X-ray powder diffraction results show that the characteristic peaks are showed at the 2[theta] of 11.4, 1
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Paragraph 0029; 0033; 0034; 0035
(2017/04/28)
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- A method for preparing fumaric acid fertile Norah approves (by machine translation)
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The invention relates to a pharmaceutical compound preparation, particularly relates to an anti-gastric acid drug fumaric acid fertile Norah approves preparation method. The synthesis route of the compound are as follows: (by machine translation)
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Paragraph 0062-0063
(2017/08/25)
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- Vonoprazan fumarate new crystal form and preparation method thereof
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The invention discloses a vonoprazan fumarate new crystal form and a preparation method thereof. The preparation method comprises the following step: taking ethyl acetate, methanol and purified water as a mixed crystallizing solvent to obtain the vonopraz
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Paragraph 0038; 0039
(2017/08/28)
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- Synthesis method of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridyl sulfonyl)-1H-pyrrole-3-methanamine fumarate TAK438
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The present invention relates to a synthesis method of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridyl sulfonyl)-1H-pyrrole-3-methanamine fumarate TAK438. The synthesis route of TAK 438 in the prior art reduces cyan into an aldehyde structure, which then perform
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- Preparation method of fumarate of pyrrole derivatives
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The invention relates to a preparation method of fumarate of pyrrole derivatives. According to the method, 3-cyano-5-(2-fluoro-phenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole (2) is taken as a starting material, hydrogenation reduction is performed with Pd/C, and 3-amiinomethyl-5-(2-fluoro-phenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole (3) is obtained; (3) and paraformaldehyde are reduced by sodium borohydride, a product is salified with fumaric acid, and a final compound vonoprazan fumarate (1) is obtained. The preparation method is simple and convenient, the yield is high, the quality is good, and industrial production is facilitated.
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Paragraph 0055; 0056; 0057; 0058; 0059
(2016/10/24)
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- METHOD FOR PRODUCING SULFONYL CHLORIDE COMPOUND
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An object of the present invention is to provide a production method of an intermediate used in the production method of a sulfonylpyrrole compound useful as a pharmaceutical product. The present invention relates to a method of producing sulfonylpyrrole compound (VI) by reacting a pyridine-3-sulfonic acid compound with phosphorus pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene to give a pyridine-3-sulfonyl chloride compound, reacting the compound without isolation with compound (III) to give compound (IV), and subjecting the compound (IV) to a reductive amination reaction. wherein R2 is a hydrocarbon group etc. and R3 and R4 are each a hydrogen atom etc., wherein R1 is an optionally substituted pyridin-3-yl group, and the other symbols are as defined above, wherein R5 is an alkyl group and the other symbols are as defined above.
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- Preparation method of drug for treating gastric acid related diseases
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The invention discloses a preparation method of a drug TAK438 for treating gastric acid related diseases. According to the preparation method, 2-bromo-2'-fluoroacetophenone is taken as the primary raw material, and the target product TAK438 is obtained through the following reactions: condensation reaction, cyclization reaction, reduction reaction, sulfonylation reaction, and reductive amination reaction. The preparation method has the advantages of easily-available raw material, easy control, and high yield, and can be applied to industrial production.
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- Polymorphic fumaric acid fertile Norah approves and its preparation method (by machine translation)
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The invention discloses a novel crystalline forms of fumaric acid fertile Norah approves A, B and method for preparing suitable for industrial production, process for preparing crystalline form of the present invention is simple, good stability, accords w
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Paragraph 0012; 0013; 0014
(2016/12/01)
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- Proton pump inhibitors
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 2 , R 3 and R 4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R 5 and R 6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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- Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3- ylsulfonyl)-1 H -pyrrol-3-yl]- n -methylmethanamine fumarate (tak-438) as a Potassium-Competitive Acid Blocker (P-CAB)
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In our pursuit of developing a novel and potent potassium-competitive acid blocker (P-CAB), we synthesized pyrrole derivatives focusing on compounds with low log"‰D and high ligand-lipophilicity efficiency (LLE) values. Among the compounds synthesized, the compound 13e exhibited potent H +,K+-ATPase inhibitory activity and potent gastric acid secretion inhibitory action in vivo. Its maximum efficacy was more potent and its duration of action was much longer than those of proton pump inhibitors (PPIs). Therefore, compound 13e (1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)- 1H-pyrrol-3-yl]-N-methylmethanamine fumarate, TAK-438) was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases.
- Arikawa, Yasuyoshi,Nishida, Haruyuki,Kurasawa, Osamu,Hasuoka, Atsushi,Hirase, Keizo,Inatomi, Nobuhiro,Hori, Yasunobu,Matsukawa, Jun,Imanishi, Akio,Kondo, Mitsuyo,Tarui, Naoki,Hamada, Teruki,Takagi, Terufumi,Takeuchi, Toshiyuki,Kajino, Masahiro
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p. 4446 - 4456
(2012/07/28)
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- PROCESS FOR PRODUCING PYRROLE COMPOUND
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The present invention provides a production method of a sulfonylpyrrole compound useful as a pharmaceutical product, a production method of an intermediate used for the method, and a novel intermediate. The present invention relates to a method of produci
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- PROTON PUMP INHIBITORS
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R2, R3 and R4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R5 and R6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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- Acid secretion inhibitor
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The present invention provides a compound having a superior acid secretion inhibitory effect and showing an antiulcer activity and the like. The present invention provides a compound represented by the formula (I) wherein R1 is a nitrogen-containing monocyclic heterocyclic group optionally condensed with a benzene ring or a heterocycle, the nitrogen-containing monocyclic heterocyclic group optionally condensed with a benzene ring or a heterocycle optionally has substituent(s), R2 is an optionally substituted C6-14 aryl group, an optionally substituted thienyl group or an optionally substituted pyridyl group, R3 and R4 are each a hydrogen atom, or one of R3 and R4 is a hydrogen atom and the other is an optionally substituted lower alkyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and R5 is an alkyl group or a salt thereof.
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Page/Page column 54
(2008/06/13)
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- PROTON PUMP INHIBITORS
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Proton pump inhibitors which have excellent proton pumping activity and which can be converted in vivo into proton pump inhibitors to exhibit antiulcer effect and so on, containing compounds represented by the general formula (I) or salts thereof or prodrugs of the same: (I) wherein X and Y are each independently a free valency or a spacer whose main chain has 1 to 20 carbon atoms; R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; R2, R3 and R4 are each independently hydrogen, an optionally substituted hydrocarbon group, optionally substituted thienyl, optionally substituted benzo[b]thienyl, optionally substituted furyl, optionally substituted pyridyl, optionally substituted pyrazolyl, optionally substituted pyrimidinyl, acyl, halogeno, cyano, or nitro; and R5 and R6 are each independently hydrogen or an optionally substituted hydrocarbon group.
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Page/Page column 338-339; 387
(2010/10/20)
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