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

Peganumine A alkaloid structure simplifier and application thereof

A technology of simplified substances and alkaloids, applied in the field of medicine, can solve the problems of difficult separation and extraction, high difficulty of total synthesis, poor water solubility, etc., and achieve the effects of strong anti-tumor activity, easy synthesis method, and easy-to-obtain synthetic raw materials

Active Publication Date: 2021-03-16
FOURTH MILITARY MEDICAL UNIVERSITY
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the alkaloid has problems such as limited sources, difficult separation and extraction, poor water solubility, high difficulty in total synthesis, and further improvement of antitumor activity (OrgLett 2014, 16, 4028-4031; J Am Chem Soc 2016, 138, 11148-11151), It limits its development into a drug, and its structure needs to be optimized to further improve its anti-tumor activity and druggability

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
  • Peganumine A alkaloid structure simplifier and application thereof
  • Peganumine A alkaloid structure simplifier and application thereof
  • Peganumine A alkaloid structure simplifier and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Synthesis of compound 1

[0044] The first step, the preparation of intermediate 6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylic acid (intermediate IV)

[0045]

[0046] Refer to the method reported in the literature (Organic Letters, 2014, 16, 4194-4197). In 50ml of water, add 5-methoxytryptamine compound II-1 (1.0g, 5.26mM) and glyoxylic acid (0.47g, 6.3mM), and stir at room temperature for 2 hours to obtain a white precipitate, which is filtered by suction and dried in vacuo to obtain Intermediate IV-1, white solid 1.16g, yield 89.6%.

[0047] The second step, the preparation of intermediate 4,9-dihydro-3H-pyrido(3,4-b)indole (intermediate VIII)

[0048]

[0049] Refer to the method reported in the literature (J Med Chem, 2015, 58, 6678-6696). In 20ml of dichloromethane, add tryptamine, compound V-1 (1.0g, 6.25mM) and ethyl formate (20ml), heat to reflux for 12 hours, evaporate the solvent to obtain 3-(2-formamidoethyl ) Indole (Intermediat...

Embodiment 2

[0055] Synthesis of Compound 2: Compound IV-2 was prepared according to the first step of the method in Example 1, and then Compound 2 was prepared according to the third step of the method in Example 1. The white solid was 66 mg, and the yield was 82%.

[0056]

Embodiment 3

[0058] Synthesis of Compound 3: Compound IV-3 was prepared according to the first step of the method in Example 1, and then Compound 3 was prepared according to the third step of the method in Example 1. The white solid was 60 mg, and the yield was 78%.

[0059]

[0060]

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
Half inhibitory concentrationaaaaaaaaaa
Login to View More

Abstract

The invention discloses a Peganumine A alkaloid structure simplifier or a medicinal salt thereof, and the structure is shown as a general formula I. The Peganumine A alkaloid structure simplificationproduct provided by the invention has obvious proliferation inhibition effect on liver cancer HepG2, lung cancer A549 and intestinal cancer HCT116, and the antitumor activity of part of compounds is stronger than that of the Peganumine A reported in literature. The Peganumine A alkaloid structure simplifier can be used as an anti-tumor lead structure for deeper research.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a Peganumine A alkaloid structure simplification and a salt thereof, a preparation method and an application. Background technique [0002] Peganumine A is a β-carboline alkaloid. According to the literature Org Lett 2014,16,4028-4031, Peganumine A has broad-spectrum anti-tumor activity, such as the IC of leukemia cell HL-60, breast cancer cell MCF-7, prostate cancer cell PC-3 and liver cancer cell HepG2 50 5.8, 8.5, 40.2 and 55.4 μM, respectively. However, the alkaloid has problems such as limited sources, difficult separation and extraction, poor water solubility, high difficulty in total synthesis, and further improvement of antitumor activity (OrgLett 2014, 16, 4028-4031; J Am Chem Soc 2016, 138, 11148-11151), This limits its development into a drug, and it is necessary to optimize its structure to further improve its anti-tumor activity and druggability. Stru...

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
IPC IPC(8): C07D471/22A61P35/00
CPCC07D471/22A61P35/00
Inventor 王胜正崔敏萱周翼鹏赵鹏帅姜茹兰杼煊张基泉同乐倩贺优优卓振建
Owner FOURTH MILITARY MEDICAL UNIVERSITY