Diosgenin hydroxamic acid derivatives as well as preparation method and application thereof

A technology of aglycone hydroxime and diosgenin soap, which is applied in the field of diosgenin hydroxamic acid derivatives and their preparation, and can solve the problems of narrow application range, low bioavailability, and poor water solubility

Active Publication Date: 2021-08-24
SOUTHWEST UNIVERSITY FOR NATIONALITIES
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as potential antitumor active substances, diosgenin and its derivatives also have disadvantages such as poor water solubility, low bioavailability, high cytotoxicity, and relatively narrow application range, so further structural modificat

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
  • Diosgenin hydroxamic acid derivatives as well as preparation method and application thereof
  • Diosgenin hydroxamic acid derivatives as well as preparation method and application thereof
  • Diosgenin hydroxamic acid derivatives as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0038] 5. The preparation method of the compound of general formula (I):

[0039]

[0040] Reagents and conditions: (1) DMAP, EDC·HCl, Dicarboxylic acids, CH2Cl2(1a-le) or DMF(lf-1i), r.t., 10h-24h, yield 56-95%.

[0041](2) CDI, NH2OH (50%), CH2Cl2 (2a-2e), r.t., 4h-6h, or. EDC·HCl, HOBt, NH2OTHP, P-TsOH, CH2Cl2 (2f-2i), r.t., 12h-18h , yield 40-87%.

[0042] Synthesis of Compound 1a_1e

[0043] Dissolve diosgenin (1.0g, 2.41mmol) in dichloromethane (30mL), add EDC·HCl (0.55g, 2.90mmol), 4-dimethylaminopyridine (0.354g, 2.90mmol), succinic anhydride (0.97g, 9.96mmol), react at 25°C for 10h, and TLC detects that the reaction is complete. The reaction solution was washed successively with 2N hydrochloric acid (3×10mL), 2N sodium bicarbonate (3×10mL), and water (3×10mL), the organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to recover dichloromethane, passed through a silica gel column Chromatography (dichloromethane:methanol (v / v)...

Embodiment

[0062] 1. Synthesis of Compound 1

[0063] Synthesis of Compound 1a

[0064] Diosgenin (1.0g, 2.41mmol, 1eq.) was dissolved in dichloromethane (30mL), and EDC·HCl (0.55g, 2.90mmol, 1.2eq.), 4-dimethylaminopyridine (0.354g, 2.90mmol, 1.2eq.), succinic anhydride (0.97g, 9.96mmol, 4eq), reacted at 25°C for 10h, and TLC detected that the reaction was complete. The reaction solution was washed successively with 2N hydrochloric acid (3×10mL), 2N sodium bicarbonate (3×10mL), and water (3×10mL), the organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to recover dichloromethane, passed through a silica gel column Chromatography (dichloromethane:methanol (v / v)=50:1) separated a white solid with a yield of 87%. m.p.222-224℃.1H NMR (400MHz, CDCl3) δ5.36 (d, J = 5.0Hz, 1H, H-6), 4.66-4.58 (m, 1H, H-3), 4.41 (q, J = 7.4Hz,1H,H-16),3.52-3.30(m,2H,H-26),2.70-2.54(m,4H,-COCH2-),2.31(d,J=7.0Hz,2H,H-4 )ppm.13C NMR (100MHz, CDCl3) δ177.36,171.52,139.53,1...

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 discloses diosgenin hydroxamic acid derivatives as well as a preparation method and application thereof. Diosgenin is used as a lead compound, a series of hydroxamic acid derivatives are prepared through corresponding chemical reactions, and the application of the derivatives in the anti-tumor aspect is also disclosed. Pharmacological experiments show that all the synthesized diosgenin hydroximic acid derivatives are subjected to in-vitro anti-proliferative activity experiments on SW620 (human colonic adenocarcinoma cells), H358 (human non-small cell lung cancer cells), HCT-116 (human colorectal adenocarcinoma cells) and Aspc-1 (human metastatic pancreatic cancer cells) by adopting a CCK8 method. Experimental results show that the anti-tumor activity of most of the derivatives on cells is superior to that of diosgenin.

Description

technical field [0001] The invention belongs to the field of diosgenin derivatives, and in particular relates to diosgenin hydroxamic acid derivatives and a preparation method and application thereof. Background technique [0002] Cancer is an extremely complex and multifactorial pathological process that can lead to abnormal proliferation of cells. It is a major public health concern and one of the main causes of global morbidity and mortality. Natural products are a good source of medicines with a wide range of pharmaceutical properties, such as antitumor activity. Whether it is naturally occurring, synthetic or semi-synthetic antineoplastic drugs, although a large number of drugs with low cytotoxicity have been developed, effective drugs have not yet been developed for many cancers. High toxicity and chemotherapy resistance are key issues that must be faced in classical anticancer therapy. Therefore, new chemotherapeutic drugs with high activity and good selectivity sho...

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): C07J71/00A61P35/00A61K31/58
CPCC07J71/0005A61P35/00
Inventor 肖雪杨鸿均王琳胡越高唐萧萧
Owner SOUTHWEST UNIVERSITY FOR NATIONALITIES
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