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Triazolo[4,5-d] pyrimidine derivatives and their application as purinergic receptor antagonists

A purine and receptor technology, applied in the field of adenosine A2A receptors and blocking adenosine receptors, which can solve problems such as no side effects

Inactive Publication Date: 2008-07-09
VERNALIS RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, option A 2A Receptor antagonists could provide effective treatment for ADHD, but without the unwanted side effects of current treatments

Method used

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  • Triazolo[4,5-d] pyrimidine derivatives and their application as purinergic receptor antagonists
  • Triazolo[4,5-d] pyrimidine derivatives and their application as purinergic receptor antagonists
  • Triazolo[4,5-d] pyrimidine derivatives and their application as purinergic receptor antagonists

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0172] Synthesis Example

[0173] The following examples shown in Table 1 can be used to illustrate the present invention.

[0174] Table 1

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[0212]

[0213] The general synthetic methods used to prepare these examples are listed below as methods A-BH. Table 2 lists the methods and analysis data used in each example.

[0214] The following conditions were used for HPLC: Column: Waters Xterra RP 18 (50×4.6mm); particle size 5μM; mobile phase: MeOH: 10mM NH 4 OAc aqueous solution (pH 7 buffer); gradient: 50:50 isocratic elution for 1 minute, then a linear gradient from 50:50 to 80:...

Embodiment 211

[0469] A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine (101mg, 0.5mmol) in DMF (2mL) was used with 2 -Bromoacetophenone (100 mg, 0.5 mmol) and triethylamine (105 μL, 0.75 mmol), stirred at room temperature for 3 days, diluted with water (100 mL) and filtered. Purify the resulting solid by chromatography [SiO 2 ;Hexane:EtOAc, (3:1-1:1)], the title compound (20mg, 13%) was obtained as a yellow solid.

[0470] Method AU

[0471] 7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine Hydrochloride (Example 213)

[0472] Add 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-2-carbaldehyde ( A solution of 62 mg, 0.193 mmol) in MeOH (20 mL) was treated with acetic acid (5 mL), dimethylamine (2-M in MeOH, 1.93 mL, 3.86 mmol) and sodium cyanoborohydride (242 mg, 3.86 mmol), Stir for 16 hours and concentrate in vacuo. The residue was treated with saturated sodium bicarbonate solution (20 mL), extracted with...

Embodiment 220

[0475] The 3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- A solution of amine (200mg, 0.517mmol) and sodium cyanide (51mg, 1.03mmol) in DMF (5mL) was stirred at 60°C for 16 hours, poured into water (40mL), extracted with EtOAc (3×8mL), and The combined organic phase is dried (MgSO 4 ), concentrated in vacuo and purified by chromatography [SiO 2 ; Isohexane: EtOAc (1:1)] to obtain the title compound (50 mg, 26%) as a yellow solid.

[0476] Method AW

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PUM

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Abstract

The use of a compound of formula (I): wherein R1 is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR5R6, NR4COR5, NR4CONR5R6, NR4CO2R7 and NR4SO2R7; R2 is selected from aryl attached via an unsaturated carbon; R3 is selected from H, alkyl, COR5, CO2R7, CONR5R6, CONR4NR5R6 and SO2R7; R4, R5 and R6 are independently selected from H, alkyl and aryl or where R5 and R6 are in an NR5R6 group, R5 and R6 may be linked to form a heterocyclic group, or where R4, R5 and R6 are in a (CONR4NR5R6) group, R4 and R5 may be linked to form a heterocyclic group; and R7 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A2A receptors, may be beneficial, particularly wherein said disorder is a movement disorder such as Parkinson's disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or for neuroprotection in a subject; compounds of formula (I) for use in therapy; and novel compounds of formula (I) per se.

Description

[0001] This application is a divisional application of the patent application with the filing date of January 10, 2002 and the application number of 02806303.1. Technical field [0002] The present invention relates to triazolo[4,5-d]pyrimidine derivatives and their application in therapy. In particular, the present invention relates to the treatment of diseases in which reduced purinergic neurotransmission can be beneficial. The present invention particularly relates to blocking adenosine receptors, especially adenosine A 2A Receptors, and treatment of sports disorders such as Parkinson's disease. Background technique [0003] Movement disorders are serious health problems, especially among the elderly. These movement disorders are often the result of brain damage. Disorders involving the basal ganglia that cause movement disorders include Parkinson's disease, Huntington's disease, and Wilson's disease. In addition, movement disorders often appear as a sequelae of cerebral ischem...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/505A61P25/28C07D487/04A61K31/00A61K31/198A61K31/519A61K45/00A61P25/00A61P25/04A61P25/14A61P25/16A61P25/20A61P25/24A61P43/00C07D519/00
CPCA61K31/00A61K31/505A61K31/519C07D487/04A61P21/04A61P25/00A61P25/02A61P25/04A61P25/14A61P25/16A61P25/18A61P25/20A61P25/24A61P25/28A61P27/02A61P43/00A61P9/00A61P9/02A61P9/10A61P3/10A61K31/195A61K2300/00
Inventor R·J·吉勒斯皮J·莱尔皮尼雷S·高尔S·J·巴姆福德G·C·斯特拉顿S·莱昂纳迪S·M·维斯
Owner VERNALIS RES
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