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

4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs

An alkyl and phenyl technology, applied in the field of 4-((phenoxyalkyl)thio)-phenoxyacetic acid and its analogs, can solve problems such as low efficacy and elevated HDL-C

Active Publication Date: 2006-12-20
JANSSEN PHARMA NV
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current therapies for hypercholesterolemia include statins, which lower LDL-C but have little effect on HDL-C, and fibrates, which are PPARα agonists but have low efficacy , can only induce a moderate increase in HDL-C

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
  • 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
  • 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
  • 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0196] If mixtures of stereoisomers are obtained during the preparation of the compounds of the present invention, these isomers can be separated by conventional techniques such as preparative chromatography. The compounds may be prepared in racemic form, either by enantiospecific synthesis or by resolution of the individual enantiomers. Said compounds may be resolved into their individual component enantiomers by standard techniques such as salt formation to form diastereomers. The compounds can also be resolved by formation of diastereomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds can be resolved using a chiral HPLC column.

[0197] Examples of such synthetic routes include Examples 1-9. Compounds similar to the target compounds of these Examples can be prepared by similar routes. The disclosed compounds are useful in basic research and as pharmaceutical formulations as described in the fol...

Embodiment A

[0232]

[0233] Compound 1

[0234] {2-Methyl-4-[2-methyl-3-(4-trifluoromethyl-phenoxy)-propylthio]-phenoxy}-acetic acid

[0235] Process A1

[0236]

[0237] To a flask containing chlorosulfonic acid (15.0 ml, 226 mmol) was slowly added ethyl (2-methylphenoxy)acetate A1a (10.0 g, 51.6 mmol) at 4°C according to Scheme A1. The mixture was stirred at 4°C for 30 minutes and at room temperature for 2 hours, then poured into ice water. The precipitated white solid was filtered, washed with water, and dried in vacuo overnight to afford 14.0 g (93%, white solid) of A1b;

[0238] 1H NMR (300MHz, CDCl 3 )δ7.87-7.84(m, 2H), 6.80(d, J=9.5Hz, 1H), 4.76(s, 2H), 4.29(q, J=7.1Hz, 2H), 2.37(s, 3H), 1.31(t, J=7.1Hz, 3H); MS(ES) m / z: 315(M+Na+).

[0239] To a solution of Alb (4.70 g, 16.1 mmol) in EtOH (20 ml) was added 4.0 M HCl in dioxane (20 ml), and then 100 mesh tin powder (9.80 g, 82.6 mmol) was added in portions. The mixture w...

Embodiment B

[0255]

[0256] Compound 2

[0257] {2-Methyl-4-[2-(4-trifluoromethyl-phenoxymethyl)-butylthio]-phenoxy}-acetic acid

[0258] Process B

[0259]

[0260] To a solution of (S)-(+)-2-phenylbutyric acid B1 (352mg, 2.14mmol) in THF (3ml) at 0°C, 1.0M BH 3 • THF complex in THF (2.14ml, 2.14mmol). The mixture was allowed to warm to room temperature, stirred at room temperature overnight, quenched with water, then with 1.0N HCl, and washed with Et 2 O extraction (3 times). The extract was dried, concentrated and subjected to column chromatography to obtain 283 mg (88%) of B2;

[0261] 1H NMR (300MHz, CDCl 3 )δ7.34-7.29 (m, 2H), 7.24-7.16 (m, 3H), 3.70 (m, 2H), 2.65 (m, 1H), 1.79-1.67 (m, 1H), 1.63-1.48 (m, 2H), 0.82 (t, J=7.4Hz, 3H); MS (ES) m / z: 173 (M+Na+).

[0262] Add B2 (283mg, 1.88mmol), pyridine (0.76ml, 9.4mmol) and DMAP (23mg, 0.19mmol) in CH2Cl at 0°C 2 (3ml), acetyl chloride (369mg, 4.70mmol) was added. The mix...

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 features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Patent Application No. 60 / 504,146, filed September 19, 2003, which is hereby incorporated by reference in its entirety. [0003] Statement Regarding Federally Funded Research or Development [0004] Research and development of the inventions described below have not received federal funding. Background of the invention [0005] Cardiovascular disease (CVD) is prevalent throughout the world, often in association with other disease states such as diabetes and obesity. Large population studies have attempted to identify risk factors for CVD; among these, high plasma levels of low-density lipoprotein cholesterol (LDL-C), high plasma levels of triglycerides (>200 mg / dl), and high-density lipoprotein cholesterol Low levels of protein cholesterol (HDL-C) is the most important factor. Currently, there are few treatments for l...

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
IPC IPC(8): C07C323/20C07C323/62C07D333/28A61K31/192A61K31/277A61K31/381A61P3/06A61P3/10C07C59/68C07C59/70C07C317/22C07C323/22C07C323/60C07D333/16
CPCC07C323/62C07C323/60C07D333/28C07C59/68C07C323/20C07D333/16C07C317/22C07C59/70A61K31/277A61K31/192A61P3/00A61P3/04A61P3/06A61P43/00A61P7/00A61P9/00A61P9/10A61P9/12A61P3/10A61K31/10C07C59/58C07C323/19
Inventor G·-H·郭R·张A·王A·R·迪安吉利斯
Owner JANSSEN PHARMA NV
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