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

Phenothiazine compound as well as preparation method and application thereof

A technology of phenothiazines and compounds, applied in the field of phenothiazines and their preparation, to achieve the effects of high reaction yield, mild reaction conditions and simple operation

Pending Publication Date: 2021-08-17
ZHENGZHOU UNIV
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report linking phenothiazine compounds with anti-tumor effects based on LSD1 targets to play an anti-tumor effect, so this study is of great value

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
  • Phenothiazine compound as well as preparation method and application thereof
  • Phenothiazine compound as well as preparation method and application thereof
  • Phenothiazine compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0039] The preparation process of compound 4 to compound 21 is as follows:

[0040]

Embodiment 1

[0042] Preparation of Compound 4: n=2,

[0043] (1) Dissolve 1a (1.99g, 10mmol) in anhydrous N,N-dimethylformamide (20mL), then add 1-bromo-3-chloropropane (1.89g, 12mmol) and sodium hydride in sequence (0.48g, 12mmol, 60% purity), reacted at room temperature, and monitored the progress of the reaction by TLC. After the reaction is complete, remove N,N-dimethylformamide by rotary evaporation, dissolve the residue in ethyl acetate, wash with water and saturated brine in turn, dry the organic phase with anhydrous magnesium sulfate, filter, and remove the solvent by rotary evaporation Afterwards, compound 2b was obtained by column chromatography. The yield was 61.8%.

[0044] 1 H NMR (400MHz, CDCl 3 )δ7.17–7.15(m, 4H), 7.06(d, J=7.5Hz, 2H), 6.94(d, J=7.5Hz, 2H), 4.08(t, J=6.5Hz, 2H), 3.67( t,J=6.1Hz,2H),2.24–2.21(m,2H). 13 C NMR (100MHz, CDCl 3)δ145.06, 144.49, 133.18, 127.64, 127.30, 127.16, 125.70, 123.01, 122.73, 122.39, 115.57, 115.29, 43.92, 42.45, 29.65. HRMS (ESI)...

Embodiment 2

[0048] Preparation of Compound 5: n=2,

[0049] The difference between embodiment 2 and embodiment 1 is that the piperazine in step (2) is replaced by N-methylpiperazine, the alkaline substance in step (4) is pyridine, sodium hydroxide, and all the other are the same as embodiment 1 . Compound 5 was prepared with a yield of 81.4%.

[0050] 1 H NMR (400MHz, CDCl 3 )δ7.15–7.12(m,4H),6.92–6.87(m,4H),3.92(t,J=6.9Hz,2H),2.50–2.47(m,10H),2.28(s,3H),1.99 –1.92(m,2H). 13 C NMR (100MHz, CDCl 3 )δ145.21, 127.44, 127.21, 125.07, 122.42, 115.51, 55.59, 54.99, 53.06, 45.87, 45.28, 24.38. HRMS (ESI) calcd for C 20 h 26 N 3 S[M+H] + ,340.1842; found, 340.1833.

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 phenothiazine compound which has the advantages of novel structural general formula and framework, high efficiency, low toxicity and better inhibitory activity on LSD1. The invention also discloses a preparation method of the compound. The preparation method has the characteristics of mild reaction conditions, simplicity in operation and high reaction yield. According to the invention, phenothiazine is taken as a raw material, active groups are respectively introduced to a parent of phenothiazine, and new phenothiazine pharmacophores are synthesized; and phenothiazine compounds are designed and synthesized by modification with piperazine, morpholine, piperidine and other groups. The compound retains the activity of phenothiazine and also has the characteristics of modification groups, so that the biological activity of original molecules is improved, and the anti-tumor activity of target molecules is improved. The invention also discloses an application of the compound in preparation of LSD1-targeted antitumor drugs, and the compound shows good inhibitory activity on LSD1 and shows good development potential.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a phenothiazine compound and its preparation method and application. Background technique [0002] Epigenetics refers to the heritable changes that occur in genetic genes without changing the DNA sequence, including DNA modification, histone modification, non-coding RNA, and nucleosome remodeling. Abnormal epigenetic regulation can lead to misexpression of genes, causing various diseases and even tumors. Histone modification is an important research direction, including acetylation, methylation, phosphorylation, hydroxylation and ubiquitination, among which acetylation and methylation are the most important. Studies have shown that they have a regulatory effect on the transcription of genes. In 2004, the first histone lysine demethylase 1 (Lysine Specific Demethylase 1, LSD1) was discovered, confirming that histone demethylation is a reversible process. The level of methylatio...

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 Applications(China)
IPC IPC(8): C07D279/26C07D417/12C07D417/06C07D279/22C07D279/28A61P35/00
CPCC07D279/26C07D417/12C07D417/06C07D279/22C07D279/28A61P35/00
Inventor 刘宏民代兴杰薛雷朋郑一超刘月娇任红梅熊小朋周影
Owner ZHENGZHOU 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