Compound, hydroxycholine M receptor antagonist, composition and application of saturated heterocyclic nitrogen containing caffeic acid derivative in preparing toadin M receptor antagonist

A technology of receptor antagonists and compounds, applied in the discovery and application of the mechanism of action of natural drug active ingredients, to achieve good effects, broaden the scope of clinical applications, and the effect of small side effects

Active Publication Date: 2017-09-05
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because atropine has effects on glands, smooth muscle, and nervous system, it has multiple side effects while treating diseases. In contrast, the discovery of M receptor antagonists with different structures, especially new compounds themselves, may have fewer side effects

Method used

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  • Compound, hydroxycholine M receptor antagonist, composition and application of saturated heterocyclic nitrogen containing caffeic acid derivative in preparing toadin M receptor antagonist
  • Compound, hydroxycholine M receptor antagonist, composition and application of saturated heterocyclic nitrogen containing caffeic acid derivative in preparing toadin M receptor antagonist
  • Compound, hydroxycholine M receptor antagonist, composition and application of saturated heterocyclic nitrogen containing caffeic acid derivative in preparing toadin M receptor antagonist

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Purification and preparation of alkaloid compounds in Anisodica tanggut

[0039] 1. Experimental instruments and reagents

[0040] The medicinal materials of scopolamine from Tanggut Mountain were collected from Qinghai, Northwest Plateau Plant Institute, and identified by teacher Mei Lijuan. Chromatographic column XCharge C18 (4.6×250mm, 7μm, Huapu Company), XCharge C18 (100×280mm, 7μm, Huapu Company), XCharge SCX (100×316mm, 7μm, Huapu Company), XCharge C18 (20×250mm , 7 μm, Huapu Company), anhydrous sodium sulfate, sodium dihydrogen phosphate dihydrate were purchased from Sinopharm Group, ethanolamine, phosphoric acid, and formic acid were purchased from Bailingwei, and preparative chromatography grade acetonitrile was purchased from Anhui Shilian.

[0041] 2. Purification and Preparation of Compounds

[0042] Extraction, extract in two batches, each batch of 25kg, add 80L ethanol for soaking, then heat and reflux for 2h, and extract three times respectiv...

Embodiment 2

[0043] Example 2 DMR signal characteristics of muscarinic M receptor antagonists on the Epic platform

[0044] 1. Method

[0045] 1.1 Cell Culture

[0046] HT29 human colon cancer cells were obtained from the Cell Bank of the Type Culture Collection, Chinese Academy of Sciences (Shanghai, China). HT29 cells were cultured in McCoy's 5A medium (GIBCO, Cat. No. 12800017, D-Glucose 4500.0 mg / L, supplemented with NaHCO) containing 10% fetal bovine serum, 50 μg / ml ampicillin, and 100 μg / ml streptomycin sulfate. 3 2.2g / L), at 37℃, volume content 5%CO 2 (air) incubator.

[0047] 1.2 Cell Activity Test Methods of Muscarinic M Receptor Antagonists

[0048] HT29 cells at 2 x 10 4 The density of cells / well was inoculated into 384-well biosensor microplate at 37°C, 5% CO by volume 2 (air) incubator for 22h, washed once with HBSS buffer before detection, and then added 30 μL HBSS buffer to each well, placed in Equilibrate incubation on the system for 1 h. After balancing A bas...

Embodiment 3

[0053] Example 3 MMPVP antagonistic activity to muscarinic M receptors

[0054] The dose-response relationship of the compound MMPVP with stronger M-receptor antagonistic activity in the activity screening was investigated by label-free cell target pharmacology. First, add 10 μL of the compound to be tested to the HT29 cells seeded 384-well biosensor microplate, in The system was monitored for 60 min, and then 10 μL of acetylcholine (16 μM) was added to continue monitoring for 60 min. The DMR signal induced by the compound is plotted against the time of action, such as image 3 a (The compound concentration was gradually diluted from 200 μM to 48.8 nM, and the corresponding DMR curve did not change much); the DMR response signal caused by the addition of acetylcholine in the second step was plotted with the action time, and the results were as follows image 3 b (The compound concentration was serially diluted from 200 μM to 48.8 nM, and the corresponding DMR signal curve...

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Abstract

The invention discloses a saturated heterocyclic nitrogen containing caffeic acid derivative separated from nightshades, or pharmacological acceptable salt of the caffeic acid derivative. The compound is a hydroxycholine M receptor antagonist and can be used for treating diseases of spasm, stenocardia, cholecystalgia, renal colic, visceral spasm and the like. An unmarked cell-targeting pharmacological technique is adopted, research on dose-effect relationship displays DMR response signals caused by antagonistic acetylcholine with compound dose dependency and shows that the compound has high hydroxycholine M receptor antagonistic activity. Compared with known M receptor antagonist atropine, scopolamine and the like, the compound is large in structural difference, and selectivity on muscle glands and the nervous system can be expectedly improved; current research shows that a hydroxycholine M receptor is related to diseases of spasm, analgesia, calm, schizophrenia and the like, and an efficient new ligand definite in action target can be provided for the related diseases.

Description

technical field [0001] The invention belongs to the field of discovery and application of the action mechanism of active ingredients of natural medicines, and relates to a caffeic acid derivative containing saturated nitrogen heterocycle, its action mechanism in antispasmodic medicine and its application. Background technique [0002] Anisodus tanguticus is a plant of the Solanaceae Anisodus genus, which is endemic to China and is called "Tangchuan Nabao" in Tibetan. It is distributed in Gansu, Tibet, Yunnan, Qinghai and other places in mainland China. It grows in areas between 2,800 meters and 4,200 meters above sea level. It usually grows on hillsides and grassy slopes. As a traditional Tibetan medicine, Tibetan medicine Tanggut scopolamine and its seeds are used as medicine, which has the effect of anesthesia and analgesia [1]. There are few reports on the chemical constituents of Tanggut anisodamine, most of which are tropane alkaloids such as hyoscyamine, scopolamine, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/06C07D207/08C07D211/12C07D211/22C07D295/03C07D295/096A61K31/40A61K31/445A61K31/4462A61P25/20A61P25/00A61P25/18A61P25/24A61P25/16A61P39/02A61P21/02
Inventor 梁鑫淼杜娜娜刘艳芳张秀莉
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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