Diketopiperazine compound as well as composition, preparation method and application thereof

A compound and application technology, applied to diketopiperazine compounds, its preparation, its composition field, can solve the problems such as not showing antitumor activity, not yet seen etc.

Inactive Publication Date: 2011-04-20
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
View PDF1 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Fructigenines and their derivatives are also a class of diketopiperazine compounds, but they have no antitumor activity on mouse breast cancer tsFT210 cells (Xin Zhihong, Fang Yuchun, Zhu Tianjiao, Duan Lin, Gu Qianqun, Zhu Weiming, Spongy-derived fungi Antitumor Active Components in Penicillium chrysogenum Sp-19, Chinese Journal of Marine Medicine, 2006, 25(6), 1-6)
And among all the fructigenine A compounds that have been recorded, there is no report of a compound with an oxygen substituent on the carbon 3 or 11a position of the diketopiperazine ring skeleton

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
  • Diketopiperazine compound as well as composition, preparation method and application thereof
  • Diketopiperazine compound as well as composition, preparation method and application thereof
  • Diketopiperazine compound as well as composition, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Embodiment 1: microbial fermentation culture and the preparation of compound I and compound II

[0066] 1. Fermentation culture and extraction of fermented products

[0067] 1) Production strain

[0068] The toxin-producing bacteria used to ferment and produce compounds I and II in this example is the Penicillium purpurogenum G591DS600S strain preserved in the General Microorganism Center of the China Microbiological Culture Collection Management Committee, and the preservation number is 4283 (CGMCC No.4283 ).

[0069] 2) Fermentation culture

[0070]According to the routine method of microbial culture, from the fungus PDA solid medium (composition: 2% glucose, 2% agar, 1.5% NaCl, prepared with 20% potato boiling liquid) test tube slant surface preserved in a refrigerator at 4°C, scrape it with an inoculation loop An appropriate amount of Penicillium purpurogenum G591DS600S was taken, streaked and inoculated on the newly prepared PDA solid medium, and activated and ...

Embodiment 2

[0088] Embodiment 2: the preparation of other formula I compound

[0089] Compound I and compound II prepared in Example 1 are respectively reacted with methyl iodide (or dimethyl sulfate) under the catalysis of a suitable catalyst to obtain the methylated product of compound I (compound of formula I, wherein R 1 =β-H,R 2 =α-OCH 3 ) and the methylation product of compound II (compound of formula I, wherein R 1 =α-OCH 3 , R 2 =β-H).

[0090] Also compound I and compound II can be reacted with ethyl iodide (or diethyl sulfate) respectively to obtain the ethylated product of compound I (compound of formula I, wherein R 1 =β-H,R 2 =α-OCH 2 CH 3 ) and the ethylated product of compound II (compound of formula I, wherein R 1 =α-OCH 2 CH 3 , R 2 =β-H).

[0091] In addition, the acetylated product of compound I (compound of formula I, wherein R 1 =β-H,R 2 =α-OCOCH 3 ) and the acetylation product of compound II (compound of formula I, wherein R 1 =α-OCOCH 3 , R 2 =β...

Embodiment 3

[0094] Embodiment 3: Antitumor activity test of compound I and compound II and derivatives thereof

[0095] 1. Experimental materials

[0096] 1) Preparation of the tested sample solution

[0097] The test samples are the pure compound I and compound II separated and purified in the above example 1, the methylated product and acetylated product of the compound I prepared in the above example 2 and the methylated product and the acetylated product of the compound II . Precisely weigh an appropriate amount of sample, and use methanol to make a solution of the required concentration for testing the activity.

[0098] 2) Subculture of cell lines and cells

[0099] The human myelogenous chronic leukemia K562 cell line was used for the activity test. K562 cells were routinely passaged with RPMI-1640 medium containing 10% fetal bovine serum and 100 μg / ml penicillin and streptomycin, and maintained at 37°C in a cell culture incubator with 5% carbon dioxide.

[0100] 2. Activity...

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 the medicine chemical industry and relates to a diketopiperazine compound as well as a composition, a preparation method and application thereof, in particular to a compound in the formula I or pharmaceutically acceptable salt thereof. In the formula I, R1 and R2 respectively and independently represent hydrogen, hydroxyl, C1-10 linear or branched alkoxy, C2-10 linear or branched alkenyl oxyl, C2-10 linear or branched alkynyl oxyl, C6-10 linear or branched aryl oxyl or C2-18 saturated or unsaturated fatty acyloxy. The invention also relates to penicillium purpurogenum for preparing the compound. Experiments prove that the compound can be used for preparing apoptosis inducers, skeleton protein inhibitors and antitumor agents. The compound provided by the invention has good antitumor activity. The formula I is shown in the specification.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to a diketopiperazine compound, a composition thereof, a preparation method and an application thereof. Background technique [0002] Tumor is a new organism formed by the body under the action of various carcinogenic factors, a certain cell in the local tissue loses its normal regulation of its growth at the gene level, resulting in abnormal clonal proliferation. Tumors are generally divided into benign and malignant. All malignant tumors are collectively called cancer. [0003] Diketopiperazine compounds are compounds containing a ring skeleton of diketopiperazine in their molecular structure, and some diketopiperazine compounds are known to have antitumor activity. [0004] Among them, tryprostatin A and B, fumitremorgin derivatives and their analogs, spirotryprostatins, cyclotryprostatins, etc. have certain anti-tumor activities, such as: blocking the cell cycle G2 / ...

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): C07D487/14C12N1/14C12P17/18A61K31/4985A61P35/00A61P35/02A61P43/00C12R1/80
Inventor 崔承彬田从魁李长伟杨明姚志伟
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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