Complex of alpha-lipoic acid H2S donor and evodiamine, and preparation method and application thereof

A technology of evodiamine and donor, applied to derivatives modified at the N-13 site, applied in the preparation of anti-tumor drugs, can solve the problems of unsuitable release control, high toxicity, and inability to be directly applied to clinical research

Active Publication Date: 2018-08-31
SHENYANG PHARMA UNIVERSITY
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its unsuitable release in the body and high toxicity, it cannot be directly used in clinical research.

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
  • Complex of alpha-lipoic acid H2S donor and evodiamine, and preparation method and application thereof
  • Complex of alpha-lipoic acid H2S donor and evodiamine, and preparation method and application thereof
  • Complex of alpha-lipoic acid H2S donor and evodiamine, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023]

[0024] Take evodiamine intermediate 2a (40mg, 0.12mmol), dissolve it in dichloromethane (5mL), add α-lipoic acid (30mg, 0.15mmol), EDCI (62mg, 0.30mmol), DMAP (4mg, 0.02mmol) ), the reaction was stirred at room temperature, the reaction progress was monitored by TCL, and the reaction was terminated after 12 hours. The reaction solution was poured into 10ml of ice-water mixture, extracted with dichloromethane (10mL×3), washed with saturated saline solution, dried over anhydrous sodium sulfate, recovered dichloromethane to obtain crude product 4a, passed through a silica gel column (petroleum ether: acetic acid Ethyl ester=10:1), separated to obtain a light yellow solid with a yield of 55%. HRMS(ESI)m / z calcd for C 29 h 33 N 3 HO 3 S 2 [M+H] + 536.2036, found 536.2057. 1 H NMR (CDCl 3 ,400MHz), δ(ppm):8.15(dd,J=7.8,1.2Hz,1H,Ar-H),7.61(d,J=7.8Hz,1H,Ar-H),7.51(td,J=7.9 ,1.2Hz,1H,Ar-H),7.45(d,J=7.9Hz,1H,Ar-H),7.31(d,J=7.2Hz,1H,Ar-H),7.28(m,1H,Ar -H),7.22(m,1H,...

Embodiment 2

[0026]

[0027] Compound 4b was prepared according to the synthesis method of Example 1. Pale yellow solid, yield 66%. HRMS(ESI)m / z:calcd for C 30 h 35 N 3 HO 3 S 2 [M+H] + 550.2193,found 550.2176. 1 H NMR (CDCl 3 ,600MHz), δ(ppm):8.14(dd,J=7.8,1.4Hz,1H,Ar-H),7.61(d,J=7.8Hz,1H,Ar-H),7.51(m,1H,Ar-H) -H),7.38(m,1H,Ar-H),7.30(m,1H,Ar-H),7.25(m,1H,Ar-H),7.21(m,1H,Ar-H),7.18( m,1H,Ar-H),5.98(s,1H,N-CH-N),4.91(m,1H,N-CH 2 ),4.54(m,1H,13-N-CH 2 ),4.28(m,1H,13-N-CH 2 ),4.17(m,1H,-COOCH 2 ),4.03(m,1H,-COOCH 2 ),3.54(m,1H,N-CH 2 ),3.20(m,2H,-CH 2 ),3.11(m,1H,-CH 2 ),3.03(m,1H,-CH 2 ),2.89(m,1H,-CH 2 ),2.45(m,1H,-CH 2 ),2.40(s,3H,N-CH 3 ),2.18(m,2H,-CH 2 ),2.12(m,2H,-CH 2),1.89(m,1H,-S-CH-),1.34–1.65(m,6H,-CH 2 ). 13 C NMR (CDCl 3 ,150MHz)δ(ppm):173.32,164.62,150.98,137.17,133.02,129.07,128.41,125.93,124.47,124.26,123.23,122.88,119.86,119.24,113.45,109.61,68.02,61.61,56.45,40.70,40.35, 39.37, 38.60, 36.48, 34.61, 33.92, 29.25, 28.82, 24.58, 20.42.

Embodiment 3

[0029]

[0030] Compound 4c was prepared according to the synthesis method of Example 1. Pale yellow solid, yield 65%. HR-MS(ESI)m / z:calcd for C 33 h 41 N 3 NaO 4 S 2 [M+Na] + 630.2431, found 630.2501. 1 H NMR (CDCl 3 ,600MHz), δ(ppm):8.13(dd,J=7.8,1.4Hz,1H,Ar-H),7.61(d,J=7.8Hz,1H,Ar-H),7.49(m,1H,Ar-H) -H),7.43(m,1H,Ar-H),7.28(m,1H,Ar-H),7.23(m,1H,Ar-H),7.20(m,1H,Ar-H),7.17( m,1H,Ar-H),6.00(s,1H,N-CH-N),4.90(m,1H,N-CH 2 ),4.56(m,1H,13-N-CH 2 ),4.28(m,1H,13-N-CH 2 ),4.08(m,1H,-COOCH 2 ),4.03(m,1H,-COOCH 2 ),3.55(m,1H,N-CH 2 ),3.42(m,1H,-CH 2 -O-CH 2 ),3.37(m,2H,-CH 2 -O-CH 2 ),3.34(m,1H,-CH 2 -O-CH 2 ),3.18(m,2H,-CH 2 ),3.10(m,1H,-CH 2 ),3.03(m,1H,-CH 2 ),2.89(m,1H,-CH 2 ),2.45(m,1H,-CH 2 ),2.40(s,3H,N-CH 3 ),2.30(m,2H,-CH 2 ),2.06(m,2H,-CH 2 ), 1.89(m,1H,-S-CH-),1.62–1.77(m,6H,-CH 2 ),1.47(m,2H,-CH 2 ). 13 CNMR (CDCl 3 ,150MHz)δ(ppm):173.51,164.69,151.02,137.35,132.94,128.98,128.62,125.79,124.18,124.13,123.13,122.68,119.66,119.05,113.16,109.9...

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 relates to the fields of natural medicines and medicinal chemistry, specifically to an alpha-lipoic acid H2S donor evodiamine derivative with antitumor activity, and pharmaceutically acceptable salts thereof. Specifically, the invention relates to the evodiamine derivative with an N-13 site substituted by an alpha-lipoic acid H2S donor and a preparation method thereof, and an application of the evodiamine derivative in preparation of antitumor drugs. The H2S donor evodiamine derivative provided by the invention and the pharmaceutically acceptable salts thereof have a structure asshown in a general formula I which is described in the specification. In the formula I, n and m are as described in the specification.

Description

technical field [0001] The invention relates to the fields of natural medicine and medicinal chemistry, and relates to derivatives modified at the N-13 site of evodiamine. Specifically related to these N-13 α-lipoic acid H 2 Evodiamine derivatives substituted by S donors, their preparation methods and their application in the preparation of antitumor drugs. Background technique [0002] Evodiamine is an indolequinazolone alkaloid compound isolated from Rutaceae Evodia plants. Evodiamine is a light yellow needle-like crystal, insoluble in water, easily soluble in dichloromethane, chloroform, soluble in methanol, ethyl acetate and other organic solvents. It has inhibitory effect on various tumor cells. Evodiamine has anti-tumor cell proliferation, inhibits the formation and invasion of tumor cell microtubules, induces tumor cell apoptosis and necrosis, and enhances cell autophagy. It is a good topoisomerase inhibitor. Studies have shown that evodiamine has a certain inhibi...

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): C07D471/14A61K31/519A61P35/00A61P35/02
Inventor 李达翃华会明胡旭李占林续繁星薛晶晶李佳
Owner SHENYANG PHARMA UNIVERSITY
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