Unlock instant, AI-driven research and patent intelligence for your innovation.

1-substituted phenanthrenyl-n-alkyl (acyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and their preparation methods and uses

A tetrahydroisoquinoline and dimethoxy technology, which can be used in drug combinations, pharmaceutical formulations, and medical preparations containing active ingredients, etc., can solve the problems of high price, high toxicity of compounds, and low bioavailability.

Active Publication Date: 2017-01-25
SHENYANG PHARMA UNIVERSITY
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Tubulin inhibitors are an important class of antineoplastic drugs. Clinically applied antineoplastic drugs acting on tubulin are mainly derived from natural plants, such as paclitaxel and vinblastine, but these compounds are highly toxic and have low bioavailability ,expensive

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
  • 1-substituted phenanthrenyl-n-alkyl (acyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and their preparation methods and uses
  • 1-substituted phenanthrenyl-n-alkyl (acyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and their preparation methods and uses
  • 1-substituted phenanthrenyl-n-alkyl (acyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and their preparation methods and uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0090] Example 1: 1-(3,6,7-trimethoxy-9-phenanthrenyl)-N-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (Compound 1) Preparation

[0091] 1) Preparation of (E)-2-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)ethanoic acid

[0092] Add 3,4-dimethoxyphenylacetic acid (19.6 g, 0.1 mol), p-methoxybenzaldehyde (16.3 g, 0.12 mol) acetic anhydride (38 mL) and triethylamine (19 mL) into a 100 mL eggplant-shaped flask , heated to reflux for 9h under the protection of argon. Stop the reaction, pour the reaction solution into hot 150mL 10% sodium hydroxide aqueous solution, heat to reflux for 0.5h, and cool down to room temperature. The solution was extracted with ether (3×100mL), the organic layer was discarded, and concentrated hydrochloric acid solution was added to the water layer in an ice bath to adjust the pH to 3. A large amount of khaki solid was precipitated, stirred for 0.5h, filtered with suction, and the filter cake was dried. 16.62 g of a khaki solid was obtained, with a...

Embodiment 2

[0107] Example 2: 1-(2,3,6,7-tetramethoxy-9-phenanthrenyl)-N-methyl-6,7-dimethoxy-1,2,3,4-tetrahydro Preparation of isoquinoline (compound 2)

[0108] The preparation process of compound 2 is the same as that of compound 1. 3,4-dimethoxybenzaldehyde and 3,4-dimethoxyphenylacetic acid are used as starting materials. After condensation, esterification, coupling, hydrolysis, acylation, cyclization, reduction, and alkylation, 1-(2,3,6,7-tetramethoxy-9-phenanthrenyl)-N-methyl- 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (compound 2), the total yield is 17.2%. 1 H-NMR (300MHz, CDCl 3 , ppm) δ: 2.25(s, 3H), 2.70(s, 1H), 2.85-2.88(d, 1H), 3.25-3.26(d, 1H), 3.40(s, 3H), 3.50(s, 1H) , 3.87(s, 3H), 3.95(s, 3H), 4.05(s, 3H), 4.07(s, 3H), 4.08(s, 3H), 4.59(s, 1H), 6.15(s, 1H), 6.63(s, 1H), 6.92(s, 1H), 7.48(s, 1H), 7.63(s, 1H), 8.31(s, 1H), 9.01(s, 1H); ESI-MS: m / z 504. 2[M+H] + .

Embodiment 3

[0109] Example 3: 1-(2-Hydroxy-3,6,7-trimethoxy-9-phenanthrenyl)-N-methyl-6,7-dimethoxy-1,2,3,4-tetra Preparation of Hydroisoquinoline (Compound 3)

[0110] The preparation process of compound 3 is similar to that of compound 2. Using 3-hydroxy-4-methoxybenzaldehyde and 3,4-dimethoxyphenylacetic acid as starting materials, after alkylation, condensation, esterification, coupling, hydrolysis, acylation, cyclization, reduction , Alkylation to get 1-(2-hydroxy-3,6,7-trimethoxy-9-phenanthrenyl)-N-methyl-6,7-dimethoxy-1,2,3,4- Tetrahydroisoquinoline.

[0111] 1-(2-Hydroxy-3,6,7-trimethoxy-9-phenanthryl)-N-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (0.25g, 0.46mmol) was dissolved in 100mL of anhydrous methanol, 30mg of 10% anhydrous Pd / C was added, 1,4 cyclohexadiene (0.26mL, 2.75mmol), ultrasonically reacted at 25°C for 1.5 hours, and Pd was filtered off / C, the filtrate was evaporated, and purified by column chromatography to obtain the target product with a total yie...

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

No PUM Login to View More

Abstract

The invention belongs to the field of drug synthesis, and relates to 1-substituted phenanthrenyl-N-alkyl (acyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and a preparation method thereof and uses. It specifically relates to a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivative with a substituted phenanthrene ring at the 1-position and a nitrogen atom substituted with an alkyl or acyl group, and a preparation method thereof and applications in medicine. The general formula of the present invention is shown in (I). In vitro anti-tumor experiments show that the compound of the present invention shows good activity and has good physiological activity; in terms of inhibiting tumor cell migration and invasion, it has a high Research value, can be further developed into a new type of anti-tumor drug. (Ⅰ).

Description

technical field [0001] The invention belongs to the field of drug synthesis, and relates to 1-substituted phenanthrenyl-N-alkyl (acyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and a preparation method thereof and uses. It specifically relates to a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivative with a phenanthrenyl group substituted at the 1-position, its preparation method and medical application. Background technique [0002] A tumor is a new organism formed by excessive proliferation or abnormal differentiation of mature or developing normal cells in the body under the action of relevant factors, usually forming a mass, hence the name tumor. Tumors are divided into two categories, benign and malignant. Malignant tumors are often called cancer, which is a common and frequently-occurring disease that seriously threatens human health. Today, cancer has become the second leading cause of death in the world. In 2007, about 7.6 million people died of c...

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 Patents(China)
IPC IPC(8): C07D217/16A61K31/472A61P35/00
CPCC07D217/16A61K31/472A61P35/00
Inventor 赵冬梅宋帅程卯生王永瑞张祯郝晨洲高禄华
Owner SHENYANG PHARMA UNIVERSITY