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Isoquinoline compound, preparation method and application of salt thereof

A technology of tetrahydroisoquinoline hydrochloride and compounds, applied in the field of preparation of antiarrhythmic drugs, capable of solving problems such as poor oral absorption and irregularity

Inactive Publication Date: 2005-01-19
JIANGSU KANION PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, berberine exhibits class III antiarrhythmic activity. It is clinically used to treat refractory ventricular tachycardia and premature ventricular, with a total effective rate of more than 60%. However, it is a quaternary ammonium salt, and its oral absorption is poor and irregular.

Method used

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  • Isoquinoline compound, preparation method and application of salt thereof
  • Isoquinoline compound, preparation method and application of salt thereof
  • Isoquinoline compound, preparation method and application of salt thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] 1-(2,5-dimethoxybenzyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride SIPI 926

[0101] (1) Mix 16.3g (0.1mol) piperonylethylamine with 19.0g (0.1mol) 2.5-dimethoxyphenylacetic acid, heat at 170-180°C for 4 hours, cool, dissolve in chloroform, and then use 2NHCl, 2NNaOH Wash with water, dry over anhydrous magnesium sulfate, evaporate the solvent under reduced pressure, and the residue is washed with EtOH-H 2 O was recrystallized to obtain 22.1 g of N-(3,4-methylenedioxyphenethyl)-3,4-dimethoxyphenylacetamide with a yield of 65% and a melting point of 119-120°C.

[0102] Elemental Analysis C 19 h 21 NO 5 Calculated %: C 66.74, H 5.87, N 4.07

[0103] Found %: C 66.46, H 6.16, N 4.08

[0104] (2) Dissolve 17g (0.05mol) of the above amide in dry chloroform, add 26ml of phosphorus oxychloride, reflux for 4 hours, evaporate the solvent and excess phosphorus oxychloride under reduced pressure, and wash the residue with petroleu...

Embodiment 2

[0111] 1-(4-methoxybenzyl)-6-methoxy-7-benzyloxy-1,2,3,4-tetrahydroisoquinoline hydrochloride SIPI 1124

[0112] (1) Use 3-methoxy-4-benzyloxyphenethylamine and 4-methoxyphenylacetic acid as raw materials to prepare the corresponding amides according to Example 1 (1).

[0113] (2) take above-mentioned amide as raw material and make corresponding dihydroisoquinoline hydrochloride by the operation of embodiment 1 (2)

[0114] (3) Using the above-mentioned dihydroisoquinoline hydrochloride as a raw material, SIPI 1124 was prepared according to Example 1 (3), with a melting point of 176-177°C.

[0115] Elemental Analysis C 25 h 28 NO 3 Cl H 2 O Calculated %: C 67.63, H6.81, N3.16, C17.99

[0116] Found %: C 67.93, H7.00, N2.85, C18.19

Embodiment 3

[0118] 1-(3-Methanesulfonamidobenzyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride C-391

[0119] (1) 8.5g (0.047mol) 3-nitrophenylacetic acid, 16ml SOCl 2 , mixed with 16ml benzene, heated to reflux for 4h, evaporated the solvent and excess SOCl under reduced pressure 2 In 3-nitrophenylacetyl chloride.

[0120] Dissolve 8g (0.04mol) of piperonylethylamine in 60ml of dichloroethane, and add 10% NaOH solution and 7.8g (0.039mol) of 3-nitrophenylacetyl chloride dropwise at 0-5°C. Alkanes solution, control pH8-9, add, stir at room temperature for 4h, precipitate solid, filter, wash with 5% HCl, wash with water, dry, recrystallize from ethanol to obtain 12.5g of N-(3,4-methylenedioxy Phenylethyl)-3-nitrophenylacetamide, the yield is 86%, and the melting point is 128-130°C.

[0121] (2) 10g iron powder and 5% NH 4 Mix 50ml of Cl solution, stir at 100°C for 20 minutes, then cool to 60°C, add 10g (0.03mol) N-(3,4-methylenedioxyphenethyl)-3-nitrophenylacetamide ...

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Abstract

The invention discloses an isoquinoline compound, preparation method and use use in preparing medicament for treating arrhythmia. The compound provided by the invention possesses strong arrhythmia resistance.

Description

technical field [0001] The invention relates to a preparation method of an isoquinoline compound and a salt thereof, and an application thereof in the preparation of a medicine for treating arrhythmia. Background technique [0002] Sudden cardiac death (SCD) is one of the leading causes of cardiovascular death. The occurrence of SCD is due to the loss of regular heart rhythm due to the instability of myocardial electrophysiology, and the most serious ones are sustained ventricular tachycardia (VT, vetriculartachycardia) and ventricular fibrillation (VF, vetricar fibrillation). [0003] Antiarrhythmic drugs can be divided into four categories: Class I is a sodium channel blocker represented by quinidine, which mainly treats supraventricular tachycardia, while Class IC flecainide, locainide, etc. Premature beats are also effective, but they all have an inhibitory effect on the myocardium. In the large-scale clinical study of CAST (Cardiac arrhthmia Suppresion Trials), it was...

Claims

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Application Information

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IPC IPC(8): A61K31/47A61K31/4709A61P9/06C07D217/18C07D401/06C07D405/06C07D409/06
Inventor 谢美华
Owner JIANGSU KANION PHARMA CO LTD
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