Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Selective butyrylcholine esterase inhibitor, preparation method and uses thereof

A butyrylcholinesterase and selective technology, which is applied in the direction of pharmaceutical formulations, organic active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of no drugs available for patients and the lack of drugs for patients with severe AD, and achieve Good in vitro activity and high selectivity

Active Publication Date: 2020-02-28
CHINA PHARM UNIV
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned drugs can only be effective for mild and moderate AD, and the drugs for severe AD patients are still very scarce, and many patients are in a situation where no drugs are available

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
  • Selective butyrylcholine esterase inhibitor, preparation method and uses thereof
  • Selective butyrylcholine esterase inhibitor, preparation method and uses thereof
  • Selective butyrylcholine esterase inhibitor, preparation method and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] (1) 6-(tert-butyl) 3-methyl 2-amino-4,7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylate (intermediate 1 )Synthesis

[0050] Take N-tert-butoxycarbonyl-4-piperidone (2g, 10.4mmol) in an eggplant-shaped bottle, dissolve it with ethanol (20mL), add methyl cyanoacetate (1.09g, 11.04mmol), and settle sulfur (0.39g , 12.05mmol) and morpholine (1.75g, 20.08mmol), heated to reflux for 3 hours, cooled to room temperature and stirred overnight, a large amount of solids were precipitated, filtered, the filter cake was washed twice with ice ethanol, dried to obtain intermediate 6- (tert-butyl) 3-methyl 2-amino-4,7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylate (2.42g, yield 77% ).

[0051] (2) 6-(tert-butyl)3-methyl 2-(benzenesulfonamido)-4,7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylic acid Synthesis of Esters (Intermediate 2)

[0052] Take 6-(tert-butyl) 3-methyl 2-amino-4,7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylate (intermediate 1, 0.5 g, 1.60mmol) in a...

Embodiment 2

[0057] Example 2: 6-Benzyl-2-(((4-methylphenyl)sulfonamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxy Synthesis of methyl esters:

[0058] With reference to the synthetic method of Example 1, the intermediate 2 in Example 1 is replaced by 6-(tert-butyl) 3-methyl 2-(((4-methylphenyl)sulfonyl)-4,7- Dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylate, a yellow solid compound, namely 6-benzyl-2-(((4-methylphenyl)sulfonyl Amino)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid methyl ester (compound 2).TLC detects as one point, there is a dark spot under the ultraviolet lamp 254nm, 365nm No fluorescence. 1 H NMR (500MHz, CDCl 3 ): δ7.79(d, J=8.2Hz, 2H), 7.40-7.30(m, 6H), 7.27(s, 1H), 3.79(s, 3H), 3.70(s, 2H), 3.52(s, 2H), 2.79(t, J=5.7Hz, 2H), 2.75(t, J=5.7Hz, 2H), 2.42(s, 3H).HRMS(ESI)m / zcalcd.for C 23 h 24 N 2 o 4 S 2 [M+H] + 456.1177, found 456.1172.

Embodiment 3

[0059] Example 3: 6-Benzyl-2-(((4-(tert-butyl)phenyl)sulfonyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine- Synthesis of methyl 3-carboxylate:

[0060] With reference to the synthetic method of Example 1, intermediate 2 in Example 1 is replaced by 6-(tert-butyl) 3-methyl 2-(((4-(tert-butyl)phenyl)sulfonamido)-4 , 7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxylate, to obtain a yellow solid compound, which is 6-benzyl-2-(((4-(tert-butyl base) phenyl) sulfonamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid methyl ester (compound 3).TLC detects as one point, UV lamp 254nm There are dark spots below and no fluorescence at 365nm. 1 H NMR (500MHz, CDCl 3 ): δ7.93(d, J=8.5Hz, 2H), 7.62(s, 1H), 7.45(d, J=8.5Hz, 2H), 7.41(t, J=6.4Hz, 3H), 7.32-7.29 (m, 2H), 4.75(s, 2H), 3.81(s, 3H), 3.55(t, J=8.3Hz, 2H), 3.26(t, J=8.4Hz, 2H), 1.32(s, 9H) .HRMS(ESI)m / z calcd.for C 26 h 30 N 2 o 4 S 2 [M+H] + 499.1647, found 499.1650.

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 a selective butyrylcholine esterase inhibitor with a structure represented by a general formula (I), a preparation method and applications thereof. According to the invention,by evaluating the effect of the selective butyrylcholine esterase inhibitor to a butyrylcholine esterase target through the cholinesterase inhibition activity and the selectivity, the results show that the selective butyrylcholine esterase inhibitor has good in-vitro activity and extremely high selectivity, and is further developed to be used in preparation of drugs for preventing or treating Alzheimer's disease.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a selective butyrylcholinesterase inhibitor, a preparation method and an application. Background technique [0002] Alzheimer's disease (AD) is a severe and irreversible degenerative syndrome of the central nervous system, clinically manifested as memory loss, cognitive deficits, mental and movement disorders, etc. [0003] The pathological causes of AD are extremely complex and involve multiple systems and links such as nerves, immunity, and blood circulation. So far, there is no conclusion about the exact cause. At present, researchers believe that AD is the result of a combination of multiple etiologies, and from the perspective of pathogenesis, more than a dozen AD theories have been proposed, such as the cholinergic theory, the amyloid (β-amyloid, Aβ) cascade theory, and the tau protein theory. , metal ion theory, oxidative stress theory, immune inflammation the...

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): C07D495/04A61P25/28A61K31/4709A61K31/4365
CPCA61P25/28C07D495/04Y02P20/55
Inventor 孙昊鹏陈霆恺杨鸿瑜杜晨曦刘弈君陈瑶冯锋柳文媛徐桔唐旭王旻宇郭凡蒋学阳
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com