Application of a long-acting compound in the preparation of medicines

A compound and compound structural formula technology, applied to the application field in the preparation of medicines, can solve the problems of limiting the long-term effect of depression and the like, and achieve the effect of long drug effect time

Active Publication Date: 2020-08-25
PEKING UNIV SHENZHEN GRADUATE SCHOOL
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] We found in animal experiments that (2R,6R; 2S,6S)-hydroxynorketamine (HNK) does not last long after administration, and loses its efficacy within 1 week, which seriously limits the treatment Expected long-term effects in depression

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
  • Application of a long-acting compound in the preparation of medicines
  • Application of a long-acting compound in the preparation of medicines
  • Application of a long-acting compound in the preparation of medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0096] Embodiment 1: compound preparation method

[0097]

[0098] Step 1: Starting from o-trifluoromethylbenzonitrile, according to the classic ketamine drug synthesis method Calvin Stevens method (preparation route as shown above) to obtain compound D 1 ;

[0099] Step 2: compound D 1 (2.57g, 10mmol) was added into 60ml THF, triethylamine (2.7mL, 20mmol) and Boc 2 O (3.32g, 15mmol), refluxed for 6h, cooled, spin-dried, and passed through a silica gel column to obtain compound E 1 3.25 g, 91% yield. 1 H NMR (300MHz, CDCl 3 ): δ7.80(d, J=8.1Hz, 1H), 7.66(d, J=7.8Hz, 1H), 7.49(t, J=7.5Hz, 1H), 7.22(t, J=7.5Hz, 1H ),5.76(s,1H),4.30(s,1H),3.46-3.42(m,1H),2.45–2.36(m,1H),2.35-2.22(m,1H),1.76–1.60(m,6H ),1.21(s,9H). 13 C NMR (75MHz, CDCl 3 ): δ208.9, 151.7, 149.0, 148.6, 136.1, 133.8, 132.6, 130.5, 129.0, 128.1, 128.0, 127.9, 127.8, 121.8, 121.7, 88.9, 80.8, 73.7, 40.0, 29.4, 28.3, 27.

[0100] Step 3: Compound E 1 (2.14g, 6mmol) was added to dry 50ml THF, under argon ...

Embodiment 2

[0103] Embodiment 2: activity test method:

[0104] 1. Forced swimming experiment

[0105] Transfer mice to the laboratory 1 h before the forced swim test (FST). The tests were performed under normal lighting conditions and monitored by a digital video camera. During the test, the mice were placed individually in transparent glass cylinders (28.5 cm high, 14 cm in diameter) containing 20 cm of water (23±1° C.). On the first day, mice were trained for 6 min before being removed from the cylinder. On the second day, mice were administered vehicle (physiological saline) control group, HNK, CF3, and then their immobility time was tested after 1 hour and 7 days, wherein immobility time refers to passive floating without other movements. During the last 4 min of the entire 6-min swim test, immobility time was recorded by the Nodus system's EthoVision XT (Noldus, Netherlands) (Castagné et al., 2011, Hajmirzaian et al., 2014, Porsolt et al., 1977). After every two to three trials,...

Embodiment 3

[0118] Embodiment 3: experimental result

[0119] 1. Depression-like behavior test results in mice:

[0120] like figure 1 Shown:

[0121] Depression-like behaviors were measured by the forced swim test. Mice received 10 mg of HNK, CF3 by intragastric administration, and immobility time was measured after 1 hour and 7 days. Percentage of immobility time is expressed as mean ± SEM *p<0.05, **p<0.0 compared to preactivity. N=8 saline per group:

[0122] Saline mice; HNK: 2R,6R-hydroxynorchloramine-treated mice; CF3, CF3-treated mice.

[0123] 2. Differential protein analysis:

[0124] like figure 2 Shown:

[0125] A, with 0.833>Abundance Ratio>1.2 as the critical point, a Ratio value higher than 1.2 is defined as an up-regulated protein, and a Ratio value lower than 0.833 is defined as a down-regulated protein. Compared with the control group, there were 101 differentially expressed proteins in the CF3 treatment group, among which 39 differentially expressed proteins ...

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

Uses of a compound having long-acting therapeutic effects in preparing a medicament. The compound is applicable in preparing a medicament for combating depression, anesthesia, pain relief, improving cognitive function, pulmonary protection, amyotrophic lateral sclerosis, and complex regional pain syndrome.

Description

technical field [0001] The application relates to the field of medicine, in particular to the application of a compound for treating depression, neurological and chronic pain, including complex regional pain syndrome (CRPS) in the preparation of medicine. Background technique [0002] Ketamine is a representative of phencyclidine intravenous anesthesia commonly used in clinical practice, and it is one of the anesthetics with rapid development in clinical and basic research in recent years. In clinical practice, it is often used to meet the anesthesia needs of pediatrics, obstetrics, perioperative period and patients with special diseases because of its characteristics of rapid induction, short action time, quick recovery, and less impact on the respiratory and circulatory systems. [0003] Ketamine was first synthesized in 1962, used in humans in 1965, and officially approved by the FDA for clinical use in 1970. Its typical "separated anesthesia" and short-acting exact anal...

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): A61K31/135A61K31/27A61P25/00A61P29/00A61P25/28A61P25/24A61P25/16A61P11/00A61P21/00A61P23/00C07C225/20
CPCA61P11/00A61P21/00A61P23/00A61P25/00A61P25/16A61P25/24A61P25/28A61P29/00C07B2200/07C07C225/20C07C2601/14Y02P20/55
Inventor 周强叶涛李书鹏
Owner PEKING UNIV SHENZHEN GRADUATE SCHOOL
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