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

Arctigenin amino-acid ester derivatives, and preparation method and application thereof

A technology of arctigenin and amino acids, which is applied in neurodegenerative disease drugs, new arctigenin amino acid ester derivatives and its preparation field, and can solve the problem of high plasma protein binding rate, low pass rate, and low bioavailability of blood-brain Barrier and other issues, to achieve the effect of easy synthesis, reasonable design, and significant neuroprotective effect

Active Publication Date: 2016-05-04
LIAONING UNIV OF TRADITIONAL CHINESE MEDICINE
View PDF3 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has strong activity (50μM level) and high plasma protein binding rate (Han Xueying; Wang Wei; Tan Riqiu; Dou Deqiang, Determination of plasma protein binding rate of arctiin and arctigenin by ultrafiltration. Chinese Journal of Traditional Chinese Medicine 2013, 38, (3 ),432-434.), low bioavailability and low blood-brain barrier passage rate limit the direct administration of arctigenin

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
  • Arctigenin amino-acid ester derivatives, and preparation method and application thereof
  • Arctigenin amino-acid ester derivatives, and preparation method and application thereof
  • Arctigenin amino-acid ester derivatives, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1: synthetic compound 1-1, please refer to figure 1 and figure 2

[0038] .

[0039] Dissolve N-Boc-L-alanine (30.4 mg, 0.16 mmol) in dry toluene, add 2,4,6-trichlorobenzoyl chloride (30.5 μL, 0.20 mmol) and DIPEA (26.0 μL, 0.20 mmol ), after stirring for 10 minutes, arctigenin (50mg, 0.134mmol) was added, DMAP (32.7mg, 0.27mmol) was added at one time, and stirring was continued at room temperature for 3h, TLC showed that the reaction was almost complete. After concentration under reduced pressure, silica gel thin-layer preparation plate was purified to obtain 63 mg of white powder with a yield of 86%. [α] D 25 =-25.6(c1.0, CHCl3 ); 1 HNMR (400MHz, CDCl 3 )δ6.96(d,J=7.3Hz,1H),6.76(d,J=9.7Hz,2H),6.67(d,J=7.9Hz,1H),6.53(d,J=8.2Hz,1H) ,6.50(s,1H),5.12(m,1H),4.58(m,1H),4.18(t,J=7.8Hz,1H),3.93–3.88(m,1H),3.85(s,3H), 3.82(s,3H),3.74(s,3H),2.97(s,2H),2.68–2.56(m,3H),2.51(m,1H),1.56(d,J=6.8Hz,3H),1.46 (s,9H);ESI-MS(m / z):[M+Na] + =566.3(Calcd:523.2).

Embodiment 2

[0040] Embodiment 2: synthetic compound 1-2, please refer to image 3 and Figure 4

[0041] .

[0042] Dissolve N-Boc-GAMMA-aminobutyric acid (32.5 mg, 0.16 mmol) with CAS No. 57294-38-9 in dry toluene, add 2,4,6-trichlorobenzoyl chloride (30.5 μL, 0.20 mmol ) and DIPEA (26.0 μL, 0.20 mmol), after stirring for 10 min, arctigenin (50 mg, 0.134 mmol) was added, and DMAP (32.7 mg, 0.27 mmol) was added at one time, and stirring was continued at room temperature for 3 h. TLC showed that the reaction was almost complete. After concentration under reduced pressure, the silica gel thin-layer preparation plate was purified to obtain 65 mg of white powder with a yield of 87%. [α] D 20 =-9.5(c1.0, CHCl 3 ). 1 HNMR (400MHz, CDCl 3 )δ6.94(d,J=7.9Hz,1H),6.83–6.72(m,2H),6.67(d,J=7.1Hz,1H),6.54(d,J=7.7Hz,1H),6.50( s,1H),4.82(s,1H),4.19–4.15(m,1H),3.93–3.88(m,1H),3.85(s,3H),3.82(s,3H),3.76(s,3H) ,3.26–3.17(m,2H),3.01–2.92(m,2H),2.66–2.57(m,4H),2.47–2.39and2.39–2.45(bothm,total2H),...

Embodiment 3

[0043] Embodiment 3: synthetic compound 1-3, please refer to Figure 5 and Figure 6

[0044] .

[0045] Dissolve N-Boc-glycine (28.0 mg, 0.16 mmol) in dry toluene, add 2,4,6-trichlorobenzoyl chloride (30.5 μL, 0.20 mmol) and DIPEA (26.0 μL, 0.20 mmol), and stir for 10 min Then arctigenin (50mg, 0.134mmol) was added, DMAP (32.7mg, 0.27mmol) was added at one time, and stirring was continued at room temperature for 3h. TLC showed that the reaction was almost complete. After concentration under reduced pressure, silica gel thin-layer preparation plate was purified to obtain 59 mg of white powder with a yield of 83%. [α] D 20 =-16.3(c1.0, CHCl 3 ), 1 HNMR (400MHz, CDCl 3 ,mixtureofrotamers)δ6.95(d,J=8.0Hz,0.7H),6.81(d,J=7.9Hz,0.3H),6.76–6.72(m,1.7H),6.67–6.62(m,1H), 6.61–6.59(m,0.3H),6.54–6.51(m,1H),6.49–6.45(m,1H),5.64(br,0.3H),5.10(br,0.7H),4.21–4.15(m, 2H), 4.15–4.07(m,1H), 3.91–3.86(m,1H), 3.84(s,3H), 3.81, 3.80 and 3.74(alls, total6H), 2.99–2.88(m,2H), 2.68 –2.41...

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 technical field of drug synthesis, and particularly relates to novel arctigenin amino-acid ester derivatives, and a preparation method and application thereof. The structure of the arctigenin amino-acid ester derivatives is disclosed as General Formula I. The preparation method comprises the following steps: dissolving amino acids and arctigenin in a solvent, adding a condensing agent in an ice bath, stirring at room temperature or in a heating state for 1-24 hours, and tracking the reaction by thin-layer chromatography; and after the reaction finishes, evaporating to remove the solvent, and purifying by silica gel column chromatography to obtain the arctigenin amino-acid ester derivatives. The preparation method is reasonable in design and easy for synthesis. The synthesized compounds have a novel chemical structure; the in-vitro cell activity experiment proves that the most synthesized amino-acid ester derivatives have an obvious neural protection action; and the compounds I-2, I-5 and I-6 have higher activity than arctigenin, and thus, provide new therapeutic drugs for preventing and treating parkinsonism and other neurodegenerative diseases.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a novel arctigenin amino acid ester derivative and a preparation method thereof, as well as its use as a drug for the preparation of neurodegenerative diseases such as Parkinson's disease (PD). Background technique [0002] Parkinson's disease (PD) is a common neurodegenerative disease. The prevalence of PD in people over 65 years old in my country is about 1.7%. Its clinical manifestations mainly include resting tremor, bradykinesia, muscle rigidity and Posture and gait disorders, while patients may be accompanied by non-motor symptoms such as depression, constipation, and sleep disturbances. Most patients with Parkinson's disease are sporadic cases, and less than 10% of patients have a family history. [0003] The main pathological change of Parkinson's disease is the degeneration and death of dopamine (DA) neurons in the substantia nigra of the midbrain, which causes a ...

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): C07D307/33A61K31/365A61P25/16A61P25/00
CPCC07D307/33
Inventor 窦德强吴平康廷国
Owner LIAONING UNIV OF TRADITIONAL CHINESE MEDICINE
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