Polymorphic substance of 5-(2-fluorophenyl)-N-methyl-(3-pyridylsulfonyl)-1H-pyrrole-3-methyl ammonium acetate

A technology of pyridylsulfonyl and carbamate, which can be applied in drug combinations, medical preparations containing active ingredients, organic chemistry, etc., and can solve the effects of poor water solubility of compounds, limiting acid suppression and treating gastric acid-related diseases and other issues to achieve good compression and good effect on lighting

Active Publication Date: 2018-03-09
JIANGSU CAREFREE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] TAK438 (5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylaminofumarate) is a potassium Ion-competitive acid blocker (P-CAB), in vitro experiments show that the ability of this compound to inhibit proton pump (H+, ATPase) is 400 times that of lansoprazole, which can effectively inhibit gastric acid secretion and has a long-lasting effect advantages, but the compound has poor water solubility, and the oral bioavailability of animals is only 10%, which limits the compound's ability to suppress acid and treat gastric acid-related diseases

Method used

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  • Polymorphic substance of 5-(2-fluorophenyl)-N-methyl-(3-pyridylsulfonyl)-1H-pyrrole-3-methyl ammonium acetate
  • Polymorphic substance of 5-(2-fluorophenyl)-N-methyl-(3-pyridylsulfonyl)-1H-pyrrole-3-methyl ammonium acetate
  • Polymorphic substance of 5-(2-fluorophenyl)-N-methyl-(3-pyridylsulfonyl)-1H-pyrrole-3-methyl ammonium acetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Crystal Form A

[0042] In a 100 mL one-necked bottle, add 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methanamine (5.0 g, 14.49 mmol) and Ethyl acetate (25 mL) was stirred and dissolved at room temperature (25°C), and glacial acetic acid (0.5 mL, 17..39 mmol) was added dropwise to the reaction system, stirred at this temperature for 60 min, solids were precipitated, and the temperature was lowered to 0-5°C, continue stirring for 1 h to filter out the solid, and wash with ethyl acetate (10 mL*2 times), and dry the obtained solid in a vacuum oven (35°C) for 4 hours to obtain 4.3 g of off-white solid, The yield was 74%.

[0043] The A crystal form of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-carbamate was subjected to powder X-ray diffraction, scanning range In the 2θ interval from 3° to 40°, the crystal structure of the compound was obtained, test conditions: 40kv 40mA; slit: 1.0 / 1.0 / Ni / 0.1; step size: 0.02°; target typ...

Embodiment 2

[0045] Example 2 Crystal Form B

[0046] In a 100 mL one-necked bottle, add 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methanamine (5.0 g, 14.49 mmol) and Ethyl acetate (25 mL) was stirred and dissolved at room temperature (25 °C), and glacial acetic acid (0.5 mL, 17.39 mmol) was added dropwise to the reaction system, stirred at this temperature for 30 min, solids were precipitated, stirred and heated to 50 ±5°C, keep warm for 1h, then lower the temperature to 2°C, and stir for 30 minutes, filter the solid, wash with ethyl acetate (20 mL*2 times), and dry the obtained solid in a vacuum oven (35°C ) for 4 hours to obtain 3.8 g of off-white solid with a yield of 65.5%.

[0047] The B crystal form of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-carbamate was subjected to powder X-ray diffraction, scanning range In the 2θ interval from 3° to 40°, the crystal structure of the compound was obtained, test conditions: 40kv 40mA; slit: 1.0 / 1.0 / Ni...

Embodiment 3

[0049] Example 3 Crystal Form C

[0050]In a 100 mL one-necked bottle, add 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methanamine (5.0 g, 14.49 mmol) and Tetrahydrofuran (50 mL) was stirred and dissolved at room temperature (25°C), and glacial acetic acid (0.5 mL, 17.39 mmol) was added dropwise to the reaction system, stirred and heated to 60°C, and stirred at this temperature for 30 minutes, then cooled to 40°C, keep stirring for 5h, then cool down to 0±5°C, and stir at this temperature for 30min, filter with suction, wash with THF (30 mL*2 times), and dry the obtained solid in a vacuum oven (35°C) 4 hours, 2.6 g of off-white solid was obtained, and the yield was 44.8%.

[0051] The C crystal form of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-carbamate was subjected to powder X-ray diffraction, scanning range In the 2θ interval from 3° to 40°, the crystal structure of the compound was obtained, test conditions: 40kv 40mA; slit: 1.0 / 1....

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Abstract

The invention relates to a novel 5-(2-fluorophenyl)-N-methyl-(3-pyridylsulfonyl)-1H-pyrrole-3-methyl ammonium acetate polymorph and describes a preparation method of each polymorph. The medicine is mainly used for treating erosive esophagitis, gastric ulcer, duodenal ulcer and helicobacter pylori and eliminating indications, and treating related diseases caused by hyperacidity.

Description

technical field [0001] The present invention relates to a potassium ion competitive acid blocker, in particular to 5-(2-fluorophenyl)-N-methyl-1-(3-pyridylsulfonyl)-1H-pyrrole-3-methylcarbamate salt polymorphs. Background technique [0002] Gastric acid-related disease is the most common type of disease in the digestive system. It refers to a general term for a type of digestive tract disease caused by excessive gastric acid secretion or being particularly sensitive to gastric acid. The common one is gastroesophageal reflux disease. , peptic ulcer, Zollinger-Ellison syndrome and digestive system diseases caused by non-steroidal anti-inflammatory drugs. Proton pump inhibitors (PPIs) are currently the most powerful class of drugs for acid suppression, such as omeprazole, lansoprazole, pantoprazole, rabeprazole, etc. Because PPIs have nocturnal acid rebound phenomenon, which affects the therapeutic effect. The emergence of potassium ion-competitive acid blockers (P-CAB) drug...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12A61K31/4439A61P1/04
CPCC07B2200/13C07D401/12
Inventor 苏梅金秋王伟
Owner JIANGSU CAREFREE PHARM CO LTD
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