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

Carboxylic acid peri-substituted bicyclics for occlusive artery disease

A technology of compounds and substituents, which is applied in the field of bicyclic acid compounds with perpositional substitution, can solve the problems of increased local concentration and low circulation level of prostaglandins, and achieve the effect of treating inflammatory diseases

Inactive Publication Date: 2007-11-21
DECODE GENETICS EHF
View PDF5 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Although circulating levels of prostanoids in healthy individuals are extremely low [FitzGerald GA, Brash AR, Falardeau P & Oates JA. JCI 1981 68:12472-1275], PGE 2 Local concentrations of may increase dramatically in inflammatory conditions

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
  • Carboxylic acid peri-substituted bicyclics for occlusive artery disease
  • Carboxylic acid peri-substituted bicyclics for occlusive artery disease
  • Carboxylic acid peri-substituted bicyclics for occlusive artery disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0159] Example 1. Preparation of A25.

[0160] 2-Fluoro-6-(naphthalen-2-yloxy)-benzonitrile (K-1): To a 20 mL vial containing a magnetic stir bar was added sodium hydride (103.7 mg, 4.32 mmol, 60% in mineral oil middle), followed by addition of anhydrous DMF (2 mL), resulting in gas evolution. To the stirred reaction mixture was added 2-naphthol (623 mg, 4.32 mmol) as a solid in small portions over a period of 5 minutes. The mixture was stirred at room temperature for 3 minutes, then a solution of 2,6-difluorobenzonitrile (601 mg, 4.32 mmol) in anhydrous DMF (4 mL) was added in one portion. The reaction mixture was heated at 100° C. in an oil bath for a total of 2 hours, then cooled to room temperature. The reaction mixture was diluted with water (15 mL), and the resulting mixture was extracted with EtOAc (2 x 20 mL). The combined organic extracts were washed with water (3 × 20 mL), dried (Na 2 SO 4 ), filtered and concentrated to give brown solid K-1 (1.216 g) (containin...

Embodiment 2

[0164] Example 2. Preparation of A26.

[0165] 4-Iodo-1-methyl-1H-indazol-3-ylamine (K-4): To a 50 mL pressure vessel was added 2-fluoro-6-iodobenzonitrile (500 mg, 2.02 mmol) and N,N - Dimethylacetamide (5 mL). To the stirred solution was added methylhydrazine (139 μL, 2.63 mmol), and the sealed vessel was heated to 80° C. for 2 hours, followed by heating at 120° C. for 16 hours. The cooled reaction mixture was diluted with water and extracted with EtOAc (3x). The combined organic extracts were washed with water and dried (Na 2 SO 4 ), filtered and concentrated. The resulting semi-solid material was triturated with hexane / EtOAc (1:1), and the resulting solid was filtered, washed with EtOAc and dried. This operation gave 149 mg of a light brown solid. The aqueous washes from the previous step were extracted with EtOAc to give an additional 327 mg of product. Total yield was 476 mg (85%) of K-4. 1H NMR, MS.

[0166] Naphthalene-2-carboxylic acid (4-iodo-1-methyl-1H-inda...

Embodiment 3

[0169] Example 3. Preparation of A02.

[0170] Synthesis of ethyl 5-amino-1-(2,2-diethoxy-ethyl)-1H-pyrazole-4-carboxylate, K-7: Hydrazine hydrate (17.5 mL, 0.355 moles) in 60 mL Bromoacetaldehyde diethyl acetal (20 g, 0.101 moles) was added dropwise to a stirred solution at reflux temperature in absolute ethanol, and the resulting mixture was heated at reflux overnight. The cooled reaction mixture was concentrated in vacuo, then 35% aqueous NaOH (25 mL) containing 3 g NaCl was added, and the solution was extracted with diethyl ether (2 x 100 mL). Combined organic phases in MgSO 4 Drying on celite and concentration in vacuo afforded 12.3 g of an oil. To a solution of this crude product (2,2-diethoxy-ethyl)-hydrazine (12.3 g, 0.0831 moles) in 25 mL of absolute ethanol was added ethylethoxymethylene cyanoacetate ( 14g, 0.0831moles) in 75mL of absolute ethanol. The mixture was stirred at room temperature for 3 days. The solvent was removed and the oily crude residue K-7 was ...

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
massaaaaaaaaaa
Login to View More

Abstract

Peri-substituted, fused bicyclic ring carboxylic acids useful for the treatment or prophylaxis of a prostaglandin-mediated disease or condition are disclosed.

Description

technical field [0001] The present invention relates to diastatically substituted bicycloacids useful in the treatment and prophylaxis of obstructive vascular diseases and related prostaglandin-mediated diseases. Background technique [0002] Atherosclerosis is the underlying pathology of several of the most lethal human diseases, such as myocardial infarction and peripheral arterial occlusive disease (PAOD). PAOD indicates atherosclerosis of the extremities, especially the large and medium arteries reaching the lower extremities, including atherosclerosis of the large and iliac arteries. It often coexists with coronary artery disease and cerebrovascular disease. People with PAOD are at increased risk of other vascular events such as myocardial infarction or stroke [Waters, RE, Terjung RL, Peters KG & Annex BH.J.Appl.Physiol.2004; Ouriel K.Lancet, 2001, 258:1257- 64; Kroger, K. Angiology, 2004, 55:135-138]. Clinically important injuries can progressively narrow peripheral...

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): C07D487/04C07D263/58C07D209/12C07D209/34C07D235/06C07D513/04A61P9/10A61K31/404
CPCC07D263/58C07D209/34C07D235/06C07D209/12C07D513/04C07D487/04C07D209/08A61P1/04A61P11/06A61P13/12A61P15/00A61P15/06A61P15/08A61P17/02A61P17/16A61P19/00A61P19/02A61P19/04A61P19/06A61P19/08A61P19/10A61P21/00A61P25/04A61P25/06A61P25/28A61P27/02A61P27/06A61P29/00A61P31/12A61P31/16A61P35/00A61P35/04A61P37/00A61P43/00A61P7/00A61P7/02A61P7/04A61P9/00A61P9/10A61P9/14
Inventor J·辛格M·格尼G·海特甘P·于D·泽姆鲍尔N·周A·波洛佐夫W·泽勒
Owner DECODE GENETICS EHF
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