8-cyclohexyl-2-fluoro-vidarabine as well as preparation method and application thereof

A technology of arabinoside nucleoside derivatives and compounds, which is applied in the fields of chemistry and medicine, can solve problems such as long history, poor treatment effect, and large drug resistance, and achieve the effect of simplifying synthesis operations and avoiding heavy metal residues

Active Publication Date: 2013-12-25
HENAN NORMAL UNIV
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] These drugs have a long history of use, high drug resistance, and poor therapeutic effect

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
  • 8-cyclohexyl-2-fluoro-vidarabine as well as preparation method and application thereof
  • 8-cyclohexyl-2-fluoro-vidarabine as well as preparation method and application thereof
  • 8-cyclohexyl-2-fluoro-vidarabine as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] In a 50mL round bottom flask, add 2-fluoro vidarabine (II, 0.29g, 1mmol), triethylamine (6.3mL, 4.5mol), 4-diaminopicoline (0.02g, 0.16mmol) and 20mL of acetonitrile, ice-water bath, keep the temperature below 5°C, add acetic anhydride (3.4mL, 3.6mmol) dropwise within 10 minutes, remove the ice-water bath, raise the temperature to 60°C, continue the reaction for 1 hour, cool down to room temperature, track with TLC The progress of the reaction shows that the reaction of the raw materials is complete. Slowly add 1 mL of methanol dropwise, remove the solvent on a rotary thin-film evaporator, add 5 mL of ethanol, stir at room temperature for 1 hour, white needle-like crystals precipitate, filter, and wash the filter cake with 5 mL of ethanol. The filter cake was dried to obtain 0.38g, yield 92% (yield is based on II), which is compound III whose hydroxyl group is protected by acetyl group, which is a colorless oil. 1 H NMR (CDCl 3 , 400MHz) δ8.90(s, 1H), 8.27(s, 1H), 6.9...

Embodiment 2

[0023] Hydroxyl-protected compound III (0.21g, 0.5mmol), peroxidized tert-butyl (0.19mL, 1mmol) and 10mL cyclohexane were added to a reaction tube equipped with a Teflon sealing plug, and reacted at 140°C for 24 hours, After cooling to room temperature, the reaction progress was followed by TLC, which showed that the reaction of the raw materials was complete. The solvent was removed on a rotary thin film evaporator, and purified by column chromatography to obtain 0.21 g of oily product 8-cyclohexyl-2-fluoro-triacetyl adenosine IV, with a yield of 85% (yield based on III). The product is a colorless oil. 1 H NMR (CDCl 3 , 400MHz) δ6.23(t, J=4.8Hz, 1H), 5.90-5.85(m, 1H), 5.81(brs, 2H), 4.50-4.47(m, 1H), 4.39-4.33(m, 2H) , 2.82-2.75(m, 1H), 2.15(s, 3H), 2.09(s, 6H), 2.04-1.97(m, 3H), 1.80-1.65(m, 8H). 13 C NMR (CDCl3, 100MHz) δ159.2 (d, J F-C2 =208.4Hz), 156.8, 156.5(d, J F-C4 =11.4Hz), 151.7(d, J F-C8 =19.3Hz), 116.7(d, J F-C5 =3.9Hz), 86.3, 80.0, 72.0, 70.2, 62.6, 36.3,...

Embodiment 3

[0025] Add 8-cyclohexyl-2-fluoro-triacetyl vidarabine IV (0.123g, 0.25mmol) and 10mL ammonia in methanol solution into the reaction bottle, seal it, and react at room temperature for 24 hours. TLC plates followed the progress of the reaction, showing complete reaction of starting materials. Remove the solvent on a rotary thin film evaporator, add methanol for recrystallization, and filter to obtain a white solid, which is 8-cyclohexyl-2-fluoro-adenosine I, 0.16 g, with a yield of 87%. (Yields are based on IV). The resulting product is a white solid. m.p.205-207 ° C. 1H NMR (DMSO-d 6 , 400MHz) δ6.33(t, J=4.8Hz, 1H), 5.91-5.88(m, 1H), 5.89(brs, 2H), 4.51-4.41(m, 1H), 4.36-4.32(m, 2H) , 2.80-2.71(m, 1H), 2.14-1.99(m, 3H), 1.82-1.66(m, 8H); 13 CNMR (DMSO-d 6 , 100MHz) δ159.8 (d, J F-C2 =208.0Hz), 157.0, 156.9(d, J F-C4 =11.4Hz), 152.0(d, J F-C8 =19.3Hz), 115.8(d, J F-C5 =3.9Hz), 86.5, 80.9, 71.7, 70.3, 62.5, 36.1, 31.0, 29.6, 25.5; HRMS: calacd for C 16 h 23 FN 5 o 4 [...

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
wavelengthaaaaaaaaaa
Login to view more

Abstract

The invention discloses an 8-cyclohexyl-2-fluoro-vidarabine, a preparation method thereof and an application of 8-cyclohexyl-2-fluoro-vidarabine to treatment of leucocythemia. By using a synthesis method disclosed by the invention, a heavy metal catalyst in the current synthesis method is avoided, the synthesis operation is simplified, heavy metal residues in 8-cyclohexyl-2-fluoro-vidarabine are avoided, and the preparation method is suitable for research and further large-scale preparation of drugs.

Description

technical field [0001] The invention belongs to the fields of chemistry and medicine, and specifically relates to 8-cyclohexyl-2-fluoroarabinosine, its preparation method and application. technical background [0002] Leukemia is a kind of clonal malignant disease with abnormal hematopoietic stem cells. The leukemia cells in its clones lose the ability to further differentiate and mature and stagnate at different stages of cell development. In the bone marrow and other hematopoietic tissues, a large number of leukemia cells proliferate and accumulate and infiltrate other organs and tissues, and at the same time inhibit normal hematopoiesis. The clinical manifestations are anemia, bleeding, infection and infiltration of various organs. [0003] Clinically used drugs for leukemia mainly include: 1. Antimetabolites, such as cytarabine, cyclocytidine, 6-mercaptopurine, etc.; 2. Drugs that affect the DNA structure and function of cancer cells, such as mitomycin, Cyclophosphamid...

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): C07H19/19C07H1/00A61K31/7076A61P35/02
Inventor 郭海明渠桂荣夏然王东超谢明胜王海霞秦博文
Owner HENAN 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