Isoquinolinium compound, producing method and application of its salt

A technology of tetrahydroisoquinoline hydrochloride and compound is applied in the application field of preparing medicine for treating antiarrhythmic diseases, and can solve the problems of irregularity, poor oral absorption and the like

Inactive Publication Date: 2008-04-02
JIANGSU KANION PHARMA CO LTD +1
View PDF0 Cites 11 Cited by
  • 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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Isoquinolinium compound, producing method and application of its salt
  • Isoquinolinium compound, producing method and application of its salt
  • Isoquinolinium compound, producing method and application of its salt

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] 1-(2,5-dimethoxybenzyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride SIPI 926

[0060] (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.

[0061] Elemental Analysis C 19 h 21 NO 5 Calculated %: C 66.74, H 5.87, N 4.07

[0062] Found %: C 66.46, H 6.16, N 4.08

[0063] (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 petroleum ether to obtain a solid ...

Embodiment 2

[0070] 1-(4-methoxybenzyl)-6-methoxy-7-benzyloxy-1,2,3,4-tetrahydroisoquinoline hydrochloride SIPI 1124

[0071] (1) Use 3-methoxy-4-benzyloxyphenethylamine and 4-methoxyphenylacetic acid as raw materials to prepare the corresponding amides according to Example 1 (1).

[0072] (2) take above-mentioned amide as raw material and make corresponding dihydroisoquinoline hydrochloride by the operation of embodiment 1 (2)

[0073] (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.

[0074] Elemental Analysis C 25 h 28 NO 3 Cl H 2 Calcd % O: C 67.63, H 6.81, N 3.16, Cl 7.99

[0075] Found %: C 67.93, H 7.00, N 2.85, Cl 8.19

Embodiment 3

[0077] 1-(3-Methanesulfonamidobenzyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride C-391

[0078] (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.

[0079] 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 get 12.5g of N-(3,4-methylenedioxybenzene Ethyl)-3-nitrophenylacetamide, the yield is 86%, and the melting point is 128-130°C.

[0080] (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 an...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to view more

Abstract

The present invention discloses a category of isoquinoline compounds or the salts as shown in the right formula, the preparation method and the application in preparation of anti-arrhythmic drugs. Wherein, R1 and R2 represent OCH3, OCH2Ph or are connected to be -OCH2O-. The compound pf the present invention has strong anti-arrhythmic activity, and in particular, has activity of blocking the potassium channel and the function of anti-chamber abnormity.

Description

[0001] The application of the present invention is a divisional application of the previous application "Preparation Method and Application of a Class of Isoquinoline Compounds and Their Salts" (application number: 03129659.9; application date: 2003.7.2). technical field [0002] 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 [0003] 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). [0004] Antiarrhythmic drugs can be divided into four categories: Class I is a sodium channel blocker represented by quinidine, which mainly treat...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/18C07D401/06C07D405/06C07D409/06A61K31/47A61K31/4709A61P9/06
Inventor 谢美华
Owner JIANGSU KANION PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap