Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Pharmaceutical compounds

a technology of benzofused and heterocyclic compounds, applied in the field of pharmaceutical compounds, can solve the problems of limited oral bioavailability and short duration of action, and achieve the effects of prolonging the duration of action, enhancing primary pharmacological properties, and improving bioavailability

Inactive Publication Date: 2011-04-14
ORION CORPORATION
View PDF13 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides new compounds that can inhibit the catechol-O-methyltransferase enzyme, which is involved in the treatment of various diseases. These compounds have improved bioavailability and longer duration of action compared to previous inhibitors. Additionally, they do not affect the energy production process and are safe for use.

Problems solved by technology

However, the commercially available COMT inhibitors are associated with a rather short duration of action and their oral bioavailability is limited.

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
  • Pharmaceutical compounds
  • Pharmaceutical compounds
  • Pharmaceutical compounds

Examples

Experimental program
Comparison scheme
Effect test

example 1

2-(4-Chloro-phenyl)-5,6-dihydroxy-4-nitro-2,3-dihydro-isoindol-1-one

2-(4-Chloro-phenyl)-5,6-dimethoxy-2,3-dihydro-isoindol-1-one

[0070] A solution of 2-bromomethyl-4,5-dimethoxy-benzoic acid methyl ester (2.9 g), 4-chloroaniline (1.28 g) and triethylamine (1.4 ml) was refluxed in toluene for six hours. The reaction mixture was stirred in an ice bath, filtered and washed with 1 M hydrochloric acid and water.

[0071] Yield: 0.74 g

[0072]1H NMR (DMSO-d6): δ=3.85 (s, 3H, CH3O), 3.88 (s, 3H, CH3O), 4.89 (s, 2H, CH2), 7.23 (s, 1H, ArH), 7.24 (s, 1H, ArH), 7.48 (d, 2H, J=8.9 Hz), 7.91 (d, 2H, J=8.9 Hz).

2-(4-Chloro-phenyl)-5,6-dihydroxy-2,3-dihydro-isoindol-1-one

[0073] 2-(4-Chloro-phenyl)-5,6-dimethoxy-2,3-dihydro-isoindol-1-one (0.74 g) was demethylated with 4 eq of boron tribromide as described in Example 8.

[0074] Yield: 0.79 g (raw material used as such in the next step)

[0075]1H NMR (DMSO-d6): δ=4.80 (s, 2H, CH2), 6.77 (s, 1H, ArH), 6.82 (s, 1H, ArH), 7.48 (d, 2H, J=9.1 Hz), 7.91 (d,...

example 2

5,6-Dihydroxy-7-nitro-3H-isobenzofuran-1-one

5,6-Dihydroxy-7-nitro-3H-isobenzofuran-1-one

[0088] To a solution of 5,6-dihydroxy-3H-isobenzofuran-1-one (0.4 g) in sulfuric acid at −30° C. was added 5 M nitric acid in sulfuric acid (0.55 ml). The reaction mixture was let to warm up to room temperature and then poured into ice water. The product was filtered and recrystallized from acetic acid.

[0089] Yield: 0.2 g

[0090]1H NMR (DMSO-d6): δ=5.26 (s, 2H, CH2), 7.14 (s, 1H, ArH), 10.6 (b, 1H, OH), 11.75 (b, 1H, OH).

example 3

7-Nitro-2-pyridin-4-yl-benzothiazole-5,6-diol, methane sulfonate

5,6-Dimethoxy-2-pyridin-4-yl-benzothiazole

[0091] A solution of 3,4-dimethoxyaniline (6 g) and sulfur (5 g) were refluxed in 4-picolin (15 ml) for five hours. The cool reaction mixture was poured into methanol, kept over ice bath for minutes and filtered. The product was washed with methanol and carbon disulfide.

[0092] Yield: 6.14 g

[0093]1H NMR (DMSO-d6): δ=3.88 (s, 3H, CH3O), 3.89 (s, 3H, CH3O), 7.67 (s, 1H, ArH), 7.76 (s, 1H, ArH), 7.94 (d, 2H, J=6.4 Hz), 8.75 (d, 2H, J=6.4 Hz).

5,6-Dimethoxy-4-nitro-2-pyridin-4-yl-benzothiazole

[0094] To a solution of 5,6-dimethoxy-2-pyridin-4-yl-benzothiazole (1.1 g) in sulfuric acid (10 ml) was added potassium nitrate (0.5 g). After 60 minutes in room temperature the mixture was poured into ice water and filtered. Recrystallization from acetone yielded the pure product.

[0095] Yield: 0.8 g

[0096]1H NMR (DMSO-d6): δ=4.05 (s, 3H, CH3O), 4.07 (s, 3H, CH3O), 8.07 (d, 2H, J=6 Hz), 8....

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
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
Login to View More

Abstract

Compounds of formula (I), wherein R1-R4, X, Y and Z are as defined in claims, exhibit COMT enzyme inhibiting activity and are thus useful as COMT inhibitors.

Description

FIELD OF THE INVENTION [0001] The present invention relates to pharmacologically active benzofused five-membered heterocycles, or pharmaceutically acceptable salts and esters thereof, as well as to pharmaceutical compositions containing them and to their use as inhibitors of catechol-O-methyltransferase (COMT) enzyme. BACKGROUND OF THE INVENTION [0002] It is generally known and accepted in the art that COMT inhibitors are useful in the treatment of Parkinson's disease. COMT inhibitors have been shown to be effective in clinical use for the treatment of Parkinson's disease as an adjunct to levodopa therapy. In order to achieve a steady plasma concentration of levodopa, it is desirable that the COMT inhibitor has a good bioavailability and a long duration of action. However, the commercially available COMT inhibitors are associated with a rather short duration of action and their oral bioavailability is limited. [0003] COMT inhibitors have also been indicated to be useful in the treat...

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(United States)
IPC IPC(8): A61K31/5377A61K31/4535A61K31/4439A61K31/428A61K31/4035A61K31/381A61K31/343C07D413/02C07D409/02C07D417/02C07D275/04C07D209/46C07D333/52C07D307/87
CPCC07D209/46C07D275/04C07D277/64C07D277/66C07D277/84C07D417/04C07D307/89C07D333/62C07D333/68C07D333/70C07D409/06C07D307/88A61P25/16A61P43/00A61K31/404A61K31/425A61K31/343
Inventor AHLMARK, MARKOBACKSTROM, REIJOLUIRO, ANNEPYSTYNEN, JARMOTIAINEN, EIJA
Owner ORION CORPORATION
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
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