Indoline diketopiperazine spiro compound and its preparation method and use

A compound and straight-chain technology, applied in the field of preparation of spiro compounds, indolin diketopiperazine spiro compounds, and indolin diketopiperazine spiro compounds, and can solve the problem that there is no literature record, etc. question

Inactive Publication Date: 2016-01-06
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the molecule has the dimer molecular skeleton formed by the condensation and connection of the above-mentioned tetracyclic indoline diketopiperazine skeleton structure and 1-oxaspiro[4,5]decane skeleton structure involved in the present invention The indoline diketopiperazine spiro compound has not been documented so far

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
  • Indoline diketopiperazine spiro compound and its preparation method and use
  • Indoline diketopiperazine spiro compound and its preparation method and use
  • Indoline diketopiperazine spiro compound and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Embodiment 1: Microbial fermentation culture and the preparation of compound 1 and compound 2

[0098] 1. Fermentation culture and extraction of fermented products

[0099] 1) Production strains

[0100] The toxin-producing bacteria used to ferment and produce compounds 1 and 2 in this example is Penicillium purpurogenum BD-1-3 (Penicillium purpurogenum BD-1-3) preserved in the General Microorganism Center of China Microbiological Culture Collection Management Committee, and the preservation number is 4284 (CGMCC No. 4283).

[0101] 2) Fermentation culture

[0102] From the PDA medium of Penicillium purpura BD-1-3 (composition: 2% glucose, 2% agar, 1.5% NaCl, prepared with 20% potato boiling liquid) test tube slant surface stored in the refrigerator at 4°C, use Scrape an appropriate amount of spores from the inoculation loop under sterile conditions, streak and inoculate them on a newly prepared PDA solid medium plate, and activate and cultivate them in a 28°C incub...

Embodiment 2

[0119] Example 2: Fermentation culture of Penicillium purpura 3-f-31 and separation and preparation of compound 1

[0120] 1. Fermentation culture and extraction of fermented products

[0121] 1) Production strains

[0122] The toxin-producing bacterium used to ferment and produce compound 1 in this example is the Penicillium purpurogenum 3-f-31 strain preserved in the General Microorganism Center of the China Microbiological Culture Collection Management Committee, and the preservation number is 7286 (CGMCCNo.7286 ).

[0123] 2) Fermentation culture

[0124] From the PDA medium (composition: 2% glucose, 2% agar, 1.5% NaCl, prepared with 20% potato boiling liquid) of the PDA medium of Penicillium purpura 3-f-31 stored in the refrigerator at 4°C, use Scrape the appropriate amount of spores from the inoculation loop under sterile conditions, streak and inoculate them on the newly prepared PDA solid medium plate, and cultivate them in a 28°C incubator for 3-5 days. When the...

Embodiment 3

[0134] Embodiment 3: Derivatization preparation of other compounds of formula I of the present invention 1a-1i and 2a-2r

[0135] 1) Derivatization preparation of compound 1a-1i of formula I of the present invention

[0136] Weigh about 10 mg of Compound 1 prepared in the above-mentioned Example 1 and Example 2, dissolve it with 0.5 ml of acetone, add 50 mg of anhydrous K 2 CO 2 Mix well, and add 50 μl methyl iodide dropwise under magnetic stirring at 60°C to carry out methylation reaction for 6 h. The reaction product was separated and purified by preparative silica gel thin-layer chromatography (chloroform-methanol volume ratio 93:7). In addition to recovering 5 mg of raw material compound 1, 1a (1.3 mg, positive ion ESI-MSm / z: 877[ M+H] + , negative ion ESI-MSm / z:875[M-H] - ).

[0137] Weigh about 10 mg of Compound 1 prepared in the above-mentioned Example 1 and Example 2, dissolve it with 0.5 ml of acetone, add 50 mg of anhydrous K 2 CO 2 Mix well, and add 50 μl d...

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
boiling pointaaaaaaaaaa
control rateaaaaaaaaaa
control rateaaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of medical and chemical industry, relates to indoline diketopiperazine spiro-compounds as well as a preparation method and use thereof, and in particular relates to compounds as shown in formula I or pharmaceutically acceptable salts of the compounds. The compounds have a framework dimerization molecular structure condensed by terracycloindoline diketopiperazine and 1-oxa spiro[4, 5] decane. Two ethylene oxide structures are arranged on the spiro hexatomic ring. The invention further relates to penicillium purpurogenum for preparing the compounds as shown in the formula I. Experiments show that the compounds can be used for preparing cytoskeletal protein inhibitors, apoptosis inducers, tumor cell proliferation inhibitors, tumor cell killing agents or antitumor drugs. The compounds provided by the invention have good antitumor activity.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to a class of spiro compounds, in particular to indoline diketopiperazine spiro compounds, and the invention also relates to a composition comprising the indoline diketopiperazine spiro compounds, And the preparation method and application of indoline diketopiperazine spiro compound. 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] The structure types of spiro compounds are very rich. Only spiro[4,5]decane compounds can form many different structural types because one or more of different positions on the spiro ring skeleton are replaced by he...

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): C07D519/00C12N1/14A61K31/4985A61P35/00A61P35/02C12R1/80
Inventor 崔承彬房士明李长伟王楠吴长景
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