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

Novel sulfated oligosaccharide derivatives

A technology of compound of general formula and monosaccharide, applied in the field of new sulfated oligosaccharide derivatives, can solve the problem of not showing anti-IIa activity and the like

Active Publication Date: 2014-12-03
PROGEN PHARMA LTD
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, PI-88 does not interact with ATIII and therefore does not exhibit anti-Xa or AT III-mediated anti-IIa activity 12，13

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
  • Novel sulfated oligosaccharide derivatives
  • Novel sulfated oligosaccharide derivatives
  • Novel sulfated oligosaccharide derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1: Dodecyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O-acetyl Base-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1→3)-2,4 , 6-tri-O-acetyl-α-D-mannopyranosyl-(1→2)-3,4,6-tri-O-acetyl-α-D-mannopyranoside (2)

[0083] trichloroacetate imidate 1 28 (0.469g, 0.285mmol) in DCM (15mL) was added 1-dodecanol (0.849mmol, 3 equiv) and MS (50 mg) Stir the mixture at -20°C for 20 min. TMSOTf (103 μL, 0.57 mmol, 2 equiv) was added and washed with Et 3 The mixture was stirred at -20°C for 50 minutes before being quenched with N (38 μL, 0.285 mmol, 1 equiv). After warming to room temperature, the mixture was filtered and the solids were rinsed with DCM. The combined filtrate and washings were evaporated on silica gel and purified by column chromatography (silica 2 x 20 cm, CHCl 3 , CHCl 3 -methanol 99:1 to 98:2 gradient elution) to obtain glycoside 2 as a colorless gum. Two fractions of BnNHAc (76 mg, 2:BnNHAc=5:3; 179 mg, 2:BnNHAc=5:...

Embodiment 2

[0088] Example 2: 12-Azido-1-dodecanol

[0089] 12-Bromo-1 was treated with sodium azide (121 mg, 1.855 mmol, 2 equiv), tetrabutylammonium iodide (17 mg, 0.0464 mmol, 0.05 equiv) and saturated aqueous sodium bicarbonate (0.9 mL) in the following order - A mixture of dodecanol (246 mg, 0.927 mmol) in tert-butanol (1.8 mL, 0.5M). The mixture was stirred at room temperature for 4 days. The mixture was filtered through a plug of Celite and the filter cake was rinsed with ethyl acetate (20 mL). The combined filtrate and washings were evaporated on silica gel and purified by flash column chromatography (2.5 x 18 cm, gradient elution with hexane-ethyl acetate 6:1, 4:1 to 2:1) to give colorless 12-Azido-1-dodecanol (193 mg, 92%) as an oil. 1 H NMR (CDCl 3, 400MHz): 3.62 (t, 2H, J=7.0, OCH 2 ), 3.24 (t, 2H, J=7.0, NCH 2 ), 1.61-1.51(m, 4H), 1.35-1.25(m, 16H).

[0090] 12-Azidododecyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1→3)-2,4,6-tri-O- Acetyl-α-D-mannopyranosyl-(1→3)-2,...

Embodiment 3

[0096] Example 3: 12-(4-Naphthyl-1-yl-[1,2,3]triazol-1-yl)dodecyl 2,3,4,6-tetra-O-acetyl-α -D-Mannopyranosyl-(1→3)-2,4,6-Tri-O-acetyl-α-D-Mannopyranosyl-(1→3)-2,4,6- Tri-O-Acetyl-α-D-Mannopyranosyl-(1→3)-2,4,6-Tri-O-Acetyl-α-D-Mannopyranosyl-(1→2 )-3,4,6-tri-O-acetyl-α-D-mannopyranoside (9)

[0097] A 1 mL HPLC vial was loaded with azide 5 (86 mg, 50.3 μmol), tert-butanol (100 μL, 0.4 M), 1-ethynylnaphthalene (83 μmol, 2 equiv), copper sulfate solution (0.3 in water) in the following order M, 14 μL, 4.2 μmol, 10 mol%) and sodium ascorbate solution (1 M in water, 12.4 μL, 12.4 μmol, 30 mol%). The mixture was stirred at room temperature for 11 days. The mixture was then evaporated on silica gel and flash column chromatography (1 x 18 cm, eluting with a gradient of hexane-ethyl acetate 6:1, 4:1, 2:1, 1:1, 1:2 to 1:3 ) was purified to give naphthyltriazole 9 (24.2 mg, 26%) as a colorless gum. 1 H NMR (CDCl 3 , 400MHz) δ8.38-8.33 (m, 1H), 7.92-7.86 (m, 2H), 7.80 (s, 1H, triaz...

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
pore sizeaaaaaaaaaa
Login to View More

Abstract

The invention relates to novel compounds that have utility as inhibitors of heparan sulfate-binding proteins; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and / or antithrombotic treatment of a mammalian subject.

Description

technical field [0001] The invention described herein relates to compounds having activity as inhibitors of heparan sulfate-binding proteins, including heparanase. In particular, the present invention relates to sulfated oligosaccharide derivatives, although the scope of the invention is not necessarily limited thereto, in particular, the present invention relates to polysulfated oligosaccharides modified with specific, highly lipophilic groups. The present invention also relates to methods of preparing the compounds, compositions comprising the compounds, and the use of the compounds and compositions thereof for anti-angiogenic, anti-metastatic, anti-inflammatory, antimicrobial, anticoagulant use in mammalian subjects and / or use in antithrombotic therapy. The compound also has the effect of preventing the above-mentioned conditions when administered to a mammalian subject. Background technique [0002] Known as PI-88 1，2 The sulfated oligosaccharide is a promising tumor ...

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 Patents(China)
IPC IPC(8): C07H11/00A61P31/00C07H15/04A61K31/7016A61P35/00C07H15/24A61K31/702A61P35/04C07H17/02A61P7/02C07H3/04C07J9/00A61P9/00C07H3/06A61P29/00C07H5/04
CPCC07H15/04C07H15/24C07H15/26C07H15/207C07H5/06C07H5/04C07H5/02C07J41/0088C07H11/00C07H17/02C07H3/04C07J17/005C07H3/06C07J41/0094A61P29/00A61P31/00A61P31/04A61P31/12A61P35/00A61P3/06A61P35/04A61P7/02A61P9/00C07J31/006C07J43/003
Inventor V·费尔罗T·卡洛丽刘立功P·N·汉德雷K·D·约翰斯通N·韦默E·T·哈蒙德
Owner PROGEN PHARMA LTD
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