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

Salicylate fatty acid derivatives

A technology of hydrates and compounds, applied in the field of treatment and/or prevention of the following diseases, which can solve the problems of stability and lack of biological specificity

Inactive Publication Date: 2012-12-12
PRONOVA BIOPHARMA NORGE
View PDF5 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] Due to their limited stability in vivo and lack of biospecificity, PUFAs have not been widely used as therapeutic agents

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
  • Salicylate fatty acid derivatives
  • Salicylate fatty acid derivatives
  • Salicylate fatty acid derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1105] Example 1: Preparation of tert-butyl 2-((5Z,8Z,11Z,14Z,17Z)-eicosan-5,8,11,14,17-penten-1-yloxy)butanoate:

[1106]

[1107] Tetrabutylammonium chloride (0.55g, 1.98mmol) was added to (5Z,8Z,11Z,14Z,17Z)-eicos-5,8,11,14,17-pentaen-1-ol (3.50 g, 12.1 mmol) in a solution in toluene (35 mL). Aqueous NaOH (50% (w / w), 11.7 mL) and tert-butyl 2-bromobutyrate (5.41 g, 24.3 mmol) were added sequentially under vigorous stirring at room temperature. The resulting mixture was heated to 50°C, and tert-butyl 2-bromobutyrate (respectively 2.70 g, 12.1 mmol; 2.70 g, 12.1 mmol; and 2.70 g, 12.1 mmol) was added after 1.5 hours, 3.5 hours and 4.5 hours, Stir for a total of 12 hours. After cooling to room temperature, ice water (25 mL) was added and the resulting two phases were separated. The organic phase was washed with 5% NaOH(aq) and brine, dried (MgSO 4 ), filtered and concentrated. The residue was purified by flash chromatography using a gradient of 0-5% EtOAc in heptane as...

Embodiment 2

[1108] Example 2: Preparation of 2-((5Z,8Z,11Z,14Z,17Z)-eicosan-5,8,11,14,17-penten-1-yloxy)butanoic acid:

[1109]

[1110] tert-butyl 2-((5Z,8Z,11Z,14Z,17Z)-eicos-5,8,11,14,17-penten-1-yloxy)butanoate (19.6g, 45.5mmol ) was dissolved in dichloromethane (DCM) (200 mL) and placed under nitrogen atmosphere. Trifluoroacetic acid (TFA) (50 mL) was added and the reaction mixture was stirred for 1 hour. Water was added and the aqueous phase was extracted twice with DCM. The combined organic extracts were washed with brine, dried (Na 2 SO 4 ), filtered and concentrated. The residue was purified by flash chromatography using a gradient of 10-20% EtOAc (also 1% FA) in heptane (containing 1% formic acid (FA)). Concentration of the appropriate fractions afforded 12.1 g (71% yield) of the title compound. 1 H-NMR (300MHz, CDCl 3 ):δ0.90-1.00(m,6H),1.50(m,2H),1.70(m,2H),1.80(m,2H),2.10(m,4H),2.80-2.90(m,8H), 3.50 (m, 1H), 3.60 (m, 1H), 3.75 (t, 1H), 5.30-5.50 (m, 10H). MS(ESI):...

Embodiment 3

[1111] Example 3: 2-((2-((5Z,8Z,11Z,14Z,17Z)-eicos-5,8,11,14,17-penten-1-yloxy)butyryl)oxy Base) the preparation of tert-butyl benzoate:

[1112]

[1113] 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) (316mg, 1.65mmol) and 4-dimethylaminopyridine (DMAP) (20mg, 0.15mmol) were added to 2-((5Z,8Z,11Z,14Z,17Z)-eicos-5,8,11,14,17-penten-1-yloxy)butanoic acid (561 mg, 1.5 mmol) in DCM (10 mL ) in solution, the reaction mixture was stirred for 10 minutes. tert-Butyl 2-hydroxybenzoate (291 mg, 1.5 mmol) was added to the mixture and stirred for 3 hours. Brine was added and the resulting two phases were separated. The aqueous phase was extracted with DCM, and the combined organic phases were dried (Na 2 SO 4 ), filtered and concentrated in vacuo. The residue was purified by flash chromatography using 5% EtOAc in heptane as eluent. Concentration of the appropriate fractions afforded 500 mg (61% yield) of the title compound. 1 H NMR (300MHz, CDCl 3 ):δ0.98(t,3H),1.11(t,3...

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

Fatty acid conjugates of salicylate derivatives and compositions thereof are disclosed. Further disclosed are methods for treating and / or preventing an inflammatory disease including inflammation and / or inflammatory bowel disease (IBD), dyslipidemia including mixed dyslipidemia and / or hypertriglyceridemia, elevated blood lipids including, e.g., triglycerides and / or cholesterol, metabolic syndrome, peripheral insulin resistance, diabetes, atherosclerosis; a method for lowering non-HDL cholesterol; and a method for raising HDL-cholesterol comprising the administration of an effective amount of at least one compound according to the present disclosure.

Description

[0001] This application claims priority to US Provisional Application No. 61 / 296,717, filed January 20, 2010, the contents of which are hereby incorporated by reference in their entirety. [0002] The present invention relates generally to fatty acid conjugates of salicylic acid derivatives, compositions and methods of use thereof. The compositions disclosed herein may include an effective amount of a fatty acid conjugate of a salicylic acid derivative. Also disclosed are methods of treating and / or preventing inflammation including, for example, inflammatory and / or inflammatory bowel disease (IBD), dyslipidemia, including mixed dyslipidemia and / or hypertriglyceridemia, elevated blood lipids , including, for example, elevated triglycerides and / or cholesterol, metabolic syndrome, peripheral insulin resistance, diabetes, and atherosclerosis; methods of lowering non-HDL cholesterol; and methods of raising HDL cholesterol comprising administering A therapeutically effective amount o...

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): C07C233/49A61K31/166A61K31/167A61K31/194A61P3/00A61P29/00C07C65/19C07C233/55C07C233/64C07C321/20
CPCC07C323/60C07C323/52C07C271/20C07C235/60C07C235/16C07C271/16C07C265/04C07C237/22C07C275/42C07C69/734C07C235/10C07C271/28C07C235/08C07C235/12C07C59/60A61P1/00A61P19/02A61P29/00A61P3/00A61P3/06A61P5/50A61P9/10A61P3/10
Inventor R.霍夫兰德T.斯克杰雷特J.罗斯曼
Owner PRONOVA BIOPHARMA NORGE
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