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Triazole derivatives and their use as nicotinic acetylcholine receptor modulators

A technology of triazole derivatives and mixtures, which is applied in the field of new triazole derivatives, and can solve problems such as complex understanding of physiological functions

Inactive Publication Date: 2011-07-20
NEUROSEARCH AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existence of different subtypes at multiple levels complicates the understanding of the physiological role of this receptor, but at the same time increases the discovery of selective compounds to improve the pharmacological profile of this class of receptors and the possible therapeutic potential of their modulators Achievement with Safer Use

Method used

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  • Triazole derivatives and their use as nicotinic acetylcholine receptor modulators
  • Triazole derivatives and their use as nicotinic acetylcholine receptor modulators
  • Triazole derivatives and their use as nicotinic acetylcholine receptor modulators

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0143] 3-Trimethylsilylethynyl-benzonitrile (intermediate compound)

[0144]

[0145] Tetrahydrofuran (50 mL) was added to 3-bromobenzonitrile (2 g, 10.9 mmol), triphenylphosphine (0.3 g, 1.1 mmol), cuprous iodide (0.21 g, 1.1 mmol) and (bistriphenylphosphine) In a mixture of palladium(II) dichloride, the mixture was degassed. Triethylamine (3.0 mL, 21.8 mmol) was added and the mixture was stirred at room temperature under nitrogen for 10 minutes. After 15 minutes. Trimethylsilylacetylene (1.4 g, 14.1 mmol) was added dropwise. The reaction mixture was stirred overnight at room temperature.

[0146] No ingredients left. The mixture was concentrated under reduced pressure, hexane (50 mL) was added to the residue and filtered. The filtrate was washed with water and evaporated to a brown solid. Yield 1.9 g (89%).

[0147] 3-Ethynyl-benzonitrile (intermediate compound)

[0148]

[0149] Potassium carbonate (1.3 g, 9.4 mmol) was added to a solution of 3-trimethylsilyle...

Embodiment 2

[0198] 5-(4-Pyridin-3-yl-[1,2,3]triazol-1-yl)-furan-2-carboxylic acid (intermediate compound)

[0199] Potassium hydroxide (0.15 g, 2.8 mmol) was added to methyl 5-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-furan-2-carboxylate (0.75 g, 2.8 mmol) in tetrahydrofuran / water (1 / 1) at 0°C. The reaction mixture was stirred at room temperature for 2 hours. Hydrochloric acid (1.5N) was added until the pH was between 5 and 6 and the solid form was isolated by filtration. The white solid was dried in vacuo. Yield 0.66 g (92%).

[0200] 5-(4-Pyridin-3-yl-[1,2,3]triazol-1-yl)-furan-2-carboxylic acid amide (intermediate compound)

[0201]

[0202] 5-(4-Pyridin-3-yl-[1,2,3]triazol-1-yl)-furan-2-carboxylic acid (0.65 g, 2.5 mmol) was added to oxalyl chloride (10 mL, 118 mmol) , N,N-Dimethylformamide (20 μL, 0.25 mmol) was added to the mixture. The reaction mixture was stirred overnight at 45 °C.

[0203] The reaction mixture was concentrated to remove oxalyl chloride, and the residue wa...

Embodiment 3

[0209] biological activity

[0210] Characterization of hα4β2 positive allosteric modulators using FLIPR

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Abstract

This invention relates to novel triazole derivatives, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Description

technical field [0001] The present invention relates to novel triazole derivatives which were found to be modulators of nicotinic acetylcholine receptors. Due to their pharmacological properties, the compounds of the present invention may be useful in the treatment of a wide variety of diseases or disorders: those involving the cholinergic systems of the central nervous system (CNS) and peripheral nervous system (PNS), those involving smooth muscle contraction diseases or disorders, endocrine diseases or disorders, diseases or disorders involving neurodegeneration, diseases or disorders involving inflammation, pain, and withdrawal symptoms resulting from cessation of chemical substance abuse. Background technique [0002] The endogenous cholinergic neurotransmitter acetylcholine exerts its biological effects through two types of cholinergic receptors, muscarinic acetylcholine receptors (mAChR) and nicotinic acetylcholine receptors (nAChR). [0003] Nicotinic acetylcholine r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/04C07D407/14A61K31/4196A61P25/00
CPCC07D407/14C07D401/04A61P1/04A61P1/12A61P1/14A61P3/04A61P3/10A61P5/24A61P9/06A61P9/10A61P9/12A61P11/06A61P15/00A61P15/06A61P15/10A61P17/00A61P17/10A61P21/00A61P25/00A61P25/02A61P25/04A61P25/06A61P25/08A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/30A61P25/32A61P25/34A61P25/36A61P29/00A61P29/02A61P31/18A61P31/22A61P43/00A61K31/4439C07D405/14
Inventor B·H·达尔G·M·奥尔森J·K·克里斯坦森D·彼得斯
Owner NEUROSEARCH AS
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