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

1-or 3-thia-benznaphthoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof

Inactive Publication Date: 2005-06-23
GLAXOSMITHKLINE ISTRAZIVACKI CENTAR ZAGREB D O O
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Said drugs act symptomatically, but they do not stop the pathological process.

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
  • 1-or 3-thia-benznaphthoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof
  • 1-or 3-thia-benznaphthoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof
  • 1-or 3-thia-benznaphthoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

8-Oxa-1-thia-benzo[e]naphtho[3,2-h]azulene-2-carboxylic acid ethyl ester (48; Table 1)

[0097] Ethyl-2-mercaptoacetate (0.005 mole) and triethyl amine (1.0 ml) were added to a pyridine solution of the compound 41 (0.005 mole in 10 ml) and the mixture was refluxed under stirring for 3 hours. Then pyridine was removed under reduced pressure. Water and ethyl acetate were added to the residue, the layers were separated and the aqueous layer was twice more extracted with ethyl acetate. The organic layer was dried on sodium sulfate and evaporated. There remained a crude product, which was purified by recrystallization or column chromatography to give a pure product in the form of a white solid.

[0098] According to the above process, starting from compounds 42-47 there were prepared and isolated: [0099] 1,8-dithia-benzo[e]naphtho[3,2-h]azulene-2-carboxylic acid ethyl ester; [0100] 3,10-dithia-benzo[e]naphtho[1,2-h]azulene-2-carboxylic acid ethyl ester; [0101] 10-oxa-3-thia-benzo[e]naphtho[1...

example 2

(8-Oxa-1-thia-benzo[e]naphtho[3,2-h]azulene-2-yl)-methanol (55; Table 1)

[0105] An ether solution of ester 48 (1.5 mmole in 20 ml) was added dropwise to a suspension of LiAIH4 in ether (5.0 mmole in 10 ml). The reaction mixture was stirred at room temperature for 2 hours. After the completion of reaction the excess of LiAIH4 was decomposed by addition of ether and water. The obtained precipitate was filtered off and the filtrate was evaporated under reduced pressure. A crude product was purified by recrystallization to obtain a pure product in the form of white crystals.

[0106] According to the above process, starting from compounds 49-54 there were prepared and isolated: [0107] (1,8-dithia-benzo[e]naphtho[3,2-h]azulene-2-yl)-methanol; [0108] (3,10-dithia-benzo[e]naphtho[1,2-h]azulene-2-yl) -methanol; [0109] (10-oxa-3-thia-benzo[e]naphtho[1,2-h]azulene-2-yl)-methanol; [0110] (11-methoxy-8-oxa-1-thia-benzo[e]naphtho[3,2-h]azulene-2-yl)-methanol; [0111] (6,7,8,9-tetrahydro-10-oxa-3-th...

example 3

a) Dimethyl-[2-(8-oxa-1-thia-benzo[e]naphtho[3,2-h]azulene-2-ylmethoxy)-ethyl]-amine

[0114] To a solution of 2-dimethylaminoethyl chloride hydrochloride (3.0 mmole) in 50% sodium hydroxide (5 ml), a catalytic amount of benzyltriethylammonium chloride and a solution of alcohol 55 (0.3 mmole) in toluene (5 ml) were added. The reaction mixture was heated under reflux and vigorous stirring for 4 hours. Then it was cooled to room temperature, diluted with water and extracted with dichloromethane. After purifying by column chromatography, a yellow oily product was isolated.

[0115]1H NMR (ppm, CDCl3): 2.31 (s, 6H); 2.60 (t, 2H); 3.68 (t, 2H); 4.78 (s, 2H); 7.18-7.50 (m, 7H); 7.73 (s, 1H); 7.80 (m, 2H); 7.90 (s, 1H); MS (m / z): 402 (MH+).

b) Dimethyl-[3-(8-oxa-1-thia-benzo[e]naphtho[3,2-h]azulene-2-ylmethoxy)-propyl]-amine

[0116] By the reaction of alcohol 55 (0.2 mmole) and 3-dimethylaminopropyl chloride hydrochloride (2.0 mmole), a yellow oily product was obtained.

[0117]1H NMR (ppm, CDCl3...

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
humidityaaaaaaaaaa
humidityaaaaaaaaaa
Login to View More

Abstract

The present invention relates to 1- or 3-thiabenzonaphthoazulene derivafives to their pharmacologically acceptable salts and solvates, to processes and intermediates for the preparation thereof as well as to their antiinflammatory effects, especially to the inhibition of tumour necrosis factor-alpha (TNF-alpha) production and the inhibition of interleukin-1 (IL-1) production as well as to their analgetic action.

Description

TECHNICAL FIELD [0001] The present invention relates to benzonaphthoazulene derivatives of tiophene class, to their pharmacologically acceptable salts and solvates, to processes and intermediates for the preparation thereof as well as to their antiinflammatory effects, especially to the inhibition of tumour necrosis factor-α (TNF-α) production and the inhibition of interleukin-1 (IL-1) production as well as to their analgetic action. PRIOR ART [0002] Some 1,3-diaza-dibenzoazulene derivatives and salts thereof are well-known as a novel class of compounds having an antiinflammatory action (U.S. Pat. No. 3,711,489, U.S. Pat. No. 4,198,421 and CA 967,573). In the literature, from the class of 1-thia-dibenzoazulenes there are disclosed derivatives substituted in 2-position with methyl, methyl-ketone, nitro group or with carboxylic group derivatives (Cagniant P G, C. R. Hebd. Sceances Acad. Sci., 1976, 283:683-686), and 1-thia-dibenzoazulene derivatives having alkyloxy substituents in 2-p...

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): A61K31/38A61K31/381C07D495/04A61K31/4025A61K31/4535A61K31/5377A61P1/04A61P9/00A61P11/00A61P11/06A61P13/12A61P17/00A61P17/06A61P19/02A61P19/06A61P25/00A61P29/00A61P31/04A61P31/12A61P31/18A61P37/02A61P37/08A61P43/00C07D333/80C07D337/16C07D413/02
CPCC07D495/04C07D333/80Y02P20/55A61P1/04A61P11/00A61P11/06A61P13/12A61P17/00A61P17/06A61P19/02A61P19/06A61P25/00A61P29/00A61P31/04A61P31/12A61P31/18A61P37/02A61P37/08A61P43/00A61P9/00C07D333/78
Inventor MERCEP, MLADENMESIC, MILANPESIC, DIJANAOZIMEC, IVANATROJKO, RUDOLF
Owner GLAXOSMITHKLINE ISTRAZIVACKI CENTAR ZAGREB D O O
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