Tetrahydrobenzothiophene compound

A technology of benzothiophene and compounds, applied in the field of tetrahydrobenzothiophene compounds, capable of solving undisclosed problems

Active Publication Date: 2013-01-09
ASTELLAS PHARMA INC
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0033] Patent Document 13 discloses a compound represented by formula (M-a) or formula (M-b), but does not disclose a compou

Method used

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  • Tetrahydrobenzothiophene compound
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  • Tetrahydrobenzothiophene compound

Examples

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Embodiment

[0271] Hereinafter, the production method of the compound of formula (I) is demonstrated in more detail based on an Example. It should be noted that the present invention is not limited to the compounds described in the following examples. In addition, the production methods of the raw material compounds are shown in the production examples, respectively. In addition, the production method of the compound of formula (I) is not limited to the production method of the specific examples shown below, and the compound of formula (I) can also be produced by a combination of these production methods or methods obvious to those skilled in the art.

[0272] In addition, the following abbreviations may be used in Examples, Production Examples, and Tables described later. Pr: Manufacturing example number, Ex: Example number, Structure: Structural formula, Syn: Manufacturing method (the number indicates that the compound of this example is produced by the same manufacturing method as the...

manufacture example 1

[0276] (1) Add a methanol solution of sodium methoxide (about 5 mol / L, 73.7 mL) dropwise to a mixture of 50.3 g of (4-nitrobenzyl) diethyl phosphonate and 500 mL of methanol under ice cooling, and stir under ice cooling 30 minutes. A mixture of 30.6 g of methyl 4-formylbenzoate and 300 mL of methanol was added dropwise to the reaction mixture over 1 hour under ice-cooling, followed by stirring at room temperature for 15 hours after the dropwise addition. The precipitate was collected by filtration to obtain 48.8 g of methyl 4-[(E)-2-(4-nitrophenyl)vinyl]benzoate as a yellow-white solid. EI: 283

[0277] (2) In a mixture of 4-[(E)-2-(4-nitrophenyl)vinyl]benzoate 48.8g, THF 600mL and N,N-dimethylformamide (DMF) 200mL Add 10% palladium / carbon (with 55% H 2 O wet) 10.0 g, and stirred at room temperature for 8 hours under a hydrogen atmosphere (1 atm). After replacing the inside of the reaction vessel with argon, the insoluble matter was removed by filtration through a Celite l...

manufacture example 2

[0279] (1) Add 4.0 mL of piperidine dropwise to a mixture of 16.5 g of 1-(4-nitrophenyl) ethanone, 16.4 g of methyl 4-formylbenzoate and 100 mL of ethanol at room temperature, and heat under reflux Stir for 8 hours. The precipitate was collected by filtration to obtain 24.6 g of a beige solid as a crude product. The crude product was suspended in 100 mL of ethanol, and stirred under reflux for 6 hours. The precipitate was collected by filtration to obtain 24.0 g of methyl 4-[3-(4-nitrophenyl)-3-oxoprop-1-en-1-yl]benzoate as a beige solid. ESI+: 312

[0280] (2) Add 5.0 g of methyl 4-[3-(4-nitrophenyl)-3-oxoprop-1-en-1-yl]benzoate and 150 mL of methanol under ice cooling under an argon atmosphere 5.0 mL of concentrated sulfuric acid was added dropwise to the mixture. Palladium / charcoal was added to the reaction mixture under ice cooling under an argon atmosphere. After replacing with hydrogen gas (3 atmospheres) at room temperature, the mixture was stirred at room temperat...

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Abstract

Disclosed is a compound which has an intestinal phosphate transporter (NPT-IIb) inhibition activity and is useful as an active ingredient for a therapeutic agent and/or a prophylactic agent for hyperphosphatemia. A tetrahydrobenzothiophene compound represented by formula (I) has an NPT-IIb inhibition activity and can be used as a prophylactic agent and/or a therapeutic agent for hyperphosphatemia. (In the formula, R1 represents -O-(lower alkyl), -(lower alkylene)-phenyl, or the like; R2 and R3 are same as or different from each other and independently represent H, a lower alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, or the like, or R2, R3 and a nitrogen atom to which R2 and R3 are bound together may form a 5- to 7-membered saturated cyclic amino group; R4's are same as or different from each other and independently represent a halogen atom, a lower alkyl group, or the like; and n represents 0 to 2.)

Description

technical field [0001] The present invention relates to a tetrahydrobenzothiophene compound useful as an active ingredient of a pharmaceutical composition, for example, a pharmaceutical composition for treating hyperphosphatemia. Background technique [0002] Phosphorus is an essential element for sustaining life and plays a very important role in various biological functions. Phosphorus is mainly absorbed from food in the form of phosphoric acid through the digestive tract, and almost all of it is excreted into urine, thereby maintaining and regulating the total amount in the body. It is known that almost all phosphoric acid is filtered in the glomeruli during the production of urine, and only the necessary amount of phosphoric acid is reabsorbed in the renal tubules. Therefore, when the glomerular filtration capacity decreases with the development of renal failure, phosphorus excretion is insufficient, resulting in an abnormal increase in serum phosphorus concentration, t...

Claims

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Application Information

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IPC IPC(8): C07D333/68A61K31/381A61K31/4025A61K31/4436A61K31/4535A61K31/496A61K31/5377A61K31/55A61P3/12A61P9/00A61P13/12A61P43/00C07D409/12
CPCA61K31/4535A61K31/454A61K31/381A61K31/496A61K31/63C07D409/12A61K31/5377A61K31/7042A61K31/4025A61K31/4436A61K31/444C07D333/68A61K31/55C07D333/66A61P13/12A61P3/00A61P3/12A61P43/00A61P7/00A61P9/00
Inventor 八谷俊一三浦理宪今村佳正加贺大辅佐藤一平森友博幸加藤浩二寺居和宏寺田央
Owner ASTELLAS PHARMA INC
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