Synthetic method of deoxyribonucleic acid (DNA) methyl transferase inhibitor

A technology of methyltransferase and synthesis method, applied in the field of medicinal chemistry synthesis, can solve the problems of complex synthesis method, leukopenia, lack of DNMT, etc., and achieve the effects of simple synthesis route, improved reaction rate, and accelerated reaction rate.

Inactive Publication Date: 2013-01-09
SHAANXI XUEQIAN NORMAL UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 5-azacytidine is a derivative of trinucleotide phosphorylation, which competitively binds to DNMT during DNA replication, resulting in the lack of DNMT during DNA synthesis and demethylation of gene sequences. This structure-related inhibition mechanism , causing inevitable cytotoxicity, and the formed protein-DNA complex can lead to various clinical adverse events such as nausea, vomiting, and leukopenia
At present, domestic and foreign studies on the synthesis of derivatives of this compound focus on the change of the group connected to the 5-position of the indole ring, and all use 5-hydroxytryptophan as the starting material, and the synthesis method is relatively complicated.

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
  • Synthetic method of deoxyribonucleic acid (DNA) methyl transferase inhibitor
  • Synthetic method of deoxyribonucleic acid (DNA) methyl transferase inhibitor
  • Synthetic method of deoxyribonucleic acid (DNA) methyl transferase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Dissolve 0.011mol phthalic anhydride (1.63g) in acetone (20mL), then add 0.010mol tryptophan (2.03g) in acetone (20mL) solution, stir at room temperature for 1h, then add 0.015mol acetic anhydride (dehydrating agent) and 0.005mol triethylamine (catalyst), reflux at a temperature of 56°C for 3 hours for acylation reaction; after the reaction is completed, the reaction solution is cooled and poured into ice water (100mL) and allowed to stand , precipitated a white solid, filtered it with suction, washed the filter cake with water three times, recrystallized from absolute ethanol, and dried in vacuo to obtain 2-(1,3-dioxo-1,3-dihydro-2H- Isoindole)-3-(1H-indole)propionic acid, white solid, 2.72g, yield 81.5%, melting point 163°C-164°C. 1 H-NMR (CD 3 OD)δ: 9.76 (s, 1H); 7.72 (s, 4H); 7.46 (d, 1H); 7.20 (d, 1H); 6.98 (t, 1H); 6.93 (s, 1H); 1H); 5.19 (m, 1H); 3.65 (m, 2H); IR(KBr)ν / cm -1 : 3340 (NH); 2916 (CH 2 ); 1751 (C=O); 1710 (C=O); 1637 (=CH); 1549, 1450 (skeletal v...

Embodiment 2

[0025] Dissolve 0.010mol phthalic anhydride (1.48g) in acetone (20mL), then add 0.010mol tryptophan (2.03g) in acetone (20mL) solution, stir at room temperature for 1h, then add 0.020mol acetic anhydride (dehydrating agent) and 0.003mol pyridine (catalyst), reflux at a temperature of 50°C for 5 hours for acylation reaction; after the reaction is completed and the reaction solution is cooled, pour the reaction solution into ice water (100mL), let stand, and precipitate White solid, filtered with suction, washed the filter cake with water three times, recrystallized from absolute ethanol, and dried in vacuo to obtain 2-(1,3-dioxo-1,3-dihydro-2H-isoindol Indole)-3-(1H-indole)propionic acid, white solid, 2.67g, yield 80%, melting point 163°C-164°C.

Embodiment 3

[0027] Dissolve 0.014mol phthalic anhydride (2.07g) in acetone (30mL), then add 0.010mol tryptophan (2.03g) in acetone (20mL) solution, stir at room temperature for 1h, then add 0.010mol acetic anhydride (dehydrating agent) and 0.010mol triethylamine (catalyst), reflux for 4h at a temperature of 60°C for acylation reaction; after the reaction is completed and the reaction solution is cooled, pour the reaction solution into ice water (100mL) and let stand , precipitated a white solid, filtered it with suction, washed the filter cake with water three times, recrystallized from absolute ethanol, and dried in vacuo to obtain 2-(1,3-dioxo-1,3-dihydro-2H- Isoindole)-3-(1H-indole)propionic acid, white solid, 2.74g, yield 82.1%, melting point 163°C-164°C.

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to view more

Abstract

The invention discloses a synthetic method of a DNA methyl transferase inhibitor. The method includes that tryptophan and phthalic anhydride serve as raw materials, and acylation reaction is conducted to obtain a compound 2-(1,3-)-dioxo-1,3-dihydro-2H-isobenzazole)-3-(1H- isobenzazole) propionic acid. According to the method, the raw materials are cheap and available, a synthetic route is simple, a catalyst is added into a reaction system, acid generated during reaction is neutralized, and the reaction rate is improved; and besides, a dehydrating agent is added to the reaction system, the reaction temperature is reduced greatly, and the reaction rate is accelerated at the same time. The 2-(1,3-)-dioxo-1,3-dihydro-2H-isobenzazole)-3-(1H- isobenzazole) propionic acid is synthetized by using the method, and the yield rate can exceed 80%.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a synthesis method of a DNA methyltransferase inhibitor. Background technique [0002] The commonly used DNA methyltransferase (DNMT) inhibitors are cytosine analogue 5-azacytidine (5-azacytidine) and derivatives (5-aza-2-Deoxycytidine), etc. These compounds can be used to treat external For tumors caused by genetic mutations, many compounds have entered phase I, phase II, and phase III clinical stages. It has been confirmed that 5-azacytidine can demethylate and restore the expression of most hypermethylated tumor-related genes in vivo and in vitro, thereby inhibiting tumors. [0003] 5-Azacytidine is a trinucleotide phosphorylated derivative that competitively binds to DNMT during DNA replication, resulting in a lack of DNMT during DNA synthesis and demethylation of gene sequences, a structure-related inhibition mechanism , causing inevit...

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): C07D209/48
Inventor 赵红岩刘建利王汉屏
Owner SHAANXI XUEQIAN NORMAL UNIV
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