Novel triazine derivative and pharmaceutical composition containing same

A compound and solvate technology, applied in the field of novel triazine derivatives and pharmaceutical compositions containing the triazine derivatives, can solve the problem of unrecorded analgesic receptor antagonism, unrecorded receptor antagonism, etc. question

Active Publication Date: 2012-03-28
SHIONOGI & CO LTD
View PDF12 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Patent Documents 8, 9, 10 and 11 describe compounds having similar structures to the compounds of the present invention, but with respect to analgesic effect and P2X 3 or P2X 2 / 3 Receptor antagonism not documented
In addition, Non-Patent Document 8 describes a compound that has a structure similar to the compound of the present invention and exhibits analgesic activity, but for P2X 3 or P2X 2 / 3 Receptor antagonism not documented

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
  • Novel triazine derivative and pharmaceutical composition containing same
  • Novel triazine derivative and pharmaceutical composition containing same
  • Novel triazine derivative and pharmaceutical composition containing same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0743] Preparation of 6-(ethylthio)-1-(4-fluorobenzyl)-3-isopropyl-1,3,5-triazine-2,4(1H,3H)-dione

[0744] [Chemical formula 62]

[0745]

[0746] To the mixture of S-ethylthiourea hydrobromide (14.8g, 80mmol) and DMF (75mL), add isopropyl isocyanate (8.2mL, 84mmol) and DBU (12.6mL, 84mmol) under ice cooling, Stir for 6 hours under ice cooling. To the reaction solution, 1,1'-carbonyldiimidazole (15.57 g, 96 mmol) and DBU (18.0 mL, 120 mmol) were added under ice cooling, and the mixture was further stirred for 2 hours. After the reaction, 2 mol / L hydrochloric acid (240 mL) was added over about 50 minutes under ice cooling, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 6-(ethylthio)-3-isopropyl-1,3,5- as a light brown solid. Triazine-2,4(1H,3H)-dione (12.29g, yield: 71%).

[0747] 1H-NMR (δppm TMS / DMSO-d6): 1.27 (6H, t, J=7.2 Hz)), ...

Embodiment 2

[0751] 1-(4-Fluorobenzyl)-6-(4-isopropoxyphenylamino)-3-isopropyl-1,3,5-triazine-2,4(1H,3H)-dione Preparation

[0752] [Chemical formula 63]

[0753]

[0754] The 6-(ethylthio)-1-(4-fluorobenzyl)-3-isopropyl-1,3,5-triazine-2,4(1H,3H)-dione (0.323g, 1mmol ), 4-isopropoxyaniline (0.907 g, 6 mmol), and 1-methyl-2-pyrrolidone (1 mL), and stirred at 230°C for 30 minutes under microwave irradiation. After the reaction, water (100 mL) was added, and extraction was performed with ethyl acetate (100 mL). After the extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure, the obtained residue was purified by silica gel column chromatography (ethyl acetate / hexane). The obtained target product was precipitated in ethyl acetate and hexane to obtain 1-(4-fluorobenzyl)-6-(4-isopropoxyphenylamino)-3-isopropyl as a colorless solid -1,3,5-triazine-2,4(1H,3H)-dione (0.21g, yield: 51%).

[0755] Melting point: 176-177°C

[0756] 1H-NMR(δppm TMS / CDCl 3 ): 1.34 (6H, d, ...

Embodiment 3

[0758] 6-(3-Chloro-4-isopropoxyphenylamino)-1-(4-chlorobenzyl)-3-isopropyl-1,3,5-triazine-2,4(1H,3H )-Diketone preparation

[0759] [Chemical formula 64]

[0760]

[0761] The 1-(4-chlorobenzyl)-6-(ethylthio)-3-isopropyl-1,3,5-triazine-2,4(1H,3H)-dione (0.60g, 1.78 mmol), 3-chloro-4-isopropoxyaniline (0.99 g, 5.3 mmol) and acetic acid (10 mL) were stirred at 90°C for 6 hours. After the reaction, the reaction solution was added to a saturated aqueous sodium hydrogen carbonate solution (100 mL), and extracted with ethyl acetate (100 mL). The extract was washed with saturated aqueous sodium hydrogen carbonate (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate / hexane). The obtained target product was precipitated in diethyl ether and hexane to obtain 6-(3-chloro-4-isopropoxyphenylamino)-1-(4-chlorobenzyl)-3 as a colorless solid -Isop...

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

Disclosed is a novel compound having P2X3 or P2X2/3 receptor antagonistic effect. Specifically disclosed is a compound represented by formula (I). (In the formula, (a) Ra and Rb combine together to form =Z, and Rc is a group represented by R1c, or alternatively (b) Rb and Rc combine together to form a bond, and Ra is a group represented by -Y-R1a; R1a and R1c each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group or the like; R2 and R3 each independently represents a substituted or unsubstituted aryl group or the like; R4a and R4b each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group or the like; X represents -N(R5)- or the like; R5 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group or the like; Y represents -O- or the like; Z represents =O or the like; and n represents an integer of 0-4.).

Description

Technical field [0001] The present invention relates to the treatment of P2X receptors, especially P2X 3 And / or P2X 2 / 3 Compounds useful for receptor-related diseases or conditions and pharmaceutical compositions containing the compounds. Background technique [0002] Adenosine triphosphate (ATP) is known as an energy source and phosphorylation substrate in cells. On the other hand, it is known that it also functions as an information transmitting substance outside the cell. It is further known that ATP is released outside the cell due to various stimuli such as cell damage, inflammation, noxious stimulation, and decrease in blood oxygen concentration, and is released outside the cell from the primary sensory nerve terminal together with other neurotransmitters. The ATP released outside the cell transmits various extracellular information via ATP receptors (Non-Patent Document 4 and Non-Patent Document 5). [0003] ATP receptors are roughly divided into the P2X family of ion chan...

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): C07D251/46A61K31/53A61K31/5377A61P13/08A61P13/10A61P21/00A61P25/00A61P25/02A61P25/06A61P25/08A61P29/00A61P43/00C07D251/52C07D401/06C07D401/12C07D401/14C07D403/04C07D403/06C07D403/12C07D405/06C07D405/12C07D409/06C07D413/12
CPCC07D405/06C07D251/52C07D403/12C07D251/46C07D403/04C07D409/06C07D405/12C07D401/06C07D403/06C07D401/14C07D401/12C07D413/12A61P7/00A61P13/00A61P13/08A61P13/10A61P21/00A61P25/00A61P25/02A61P25/04A61P25/06A61P25/08A61P29/00A61P43/00C07D251/16C07D251/44A61K31/53
Inventor 甲斐浩幸龟山贵之长谷川刚大原美穗多田幸男远藤毅
Owner SHIONOGI & CO LTD
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
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap