Novel alpha-amino amide derivatives and pharmaceutical use thereof

A pharmacy and compound technology, applied in the field of new α-aminoamide derivatives and their medical applications, can solve the problem that the analgesic activity of Ralfinamide needs to be further improved

Active Publication Date: 2017-12-29
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the analgesic activity and target selec

Method used

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  • Novel alpha-amino amide derivatives and pharmaceutical use thereof
  • Novel alpha-amino amide derivatives and pharmaceutical use thereof
  • Novel alpha-amino amide derivatives and pharmaceutical use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1 (2S)-2-(4-(pyridine-2-oxymethyl) benzyl) amino-propionamide (Ia-1) synthesis

[0044]

[0045] 1.1 Synthesis of 4-hydroxymethylbenzaldehyde (II-1)

[0046] Take a 500mL eggplant-shaped bottle, add 20g of terephthalaldehyde (0.15mol; 4.0equiv), 100ml of ethanol and 150ml of tetrahydrofuran into the bottle in turn, stir and dissolve evenly. Then, under ice-bath conditions, slowly add 1.7g of sodium borohydride solid (9.3mmol; 1.0equiv) to the bottle at one time, react for more than 6h, spot the plate with thin-layer TLC, and monitor the reaction progress with an ultraviolet analyzer (254nm). After the raw material point of terephthalaldehyde completely disappears, stop the reaction, add dropwise the 2mol / L hydrochloric acid solution prepared in advance to quench, adjust the pH value to 4-5, and then rotate the reaction solution to dryness, and the obtained residue is water, acetic acid Ethyl ester was redissolved and added to a separatory funnel. The aqu...

Embodiment 2

[0053] Synthesis of Example 2 (2S)-2-(4-(pyridine-3-oxymethyl)benzyl)amino-propionamide (Ia-2)

[0054]

[0055] 2.1 Preparation of 4-(pyridine-3-oxymethyl)-benzaldehyde (IV-1b)

[0056] Take a 250mL eggplant-shaped bottle, weigh 1.0g intermediate III-1 (5.0mmol; 1.0equiv), 0.48g 3-hydroxypyridine (5.0mmol; 1.0equiv), 2.1g potassium carbonate (15.0mmol; 3.0equiv) , 0.6g of potassium iodide (3.0mmol; 0.6equiv), and 60mL of acetone were added to the bottle, stirred evenly, then heated to 58°C for reflux reaction for 24h, spotted by thin-layer TLC, and monitored by an ultraviolet analyzer (254nm). Then the reaction solution was filtered and evaporated to dryness, and the resulting residue was redissolved with 2mol / L NaOH aqueous solution and ethyl acetate and added to a separatory funnel. The aqueous phase was extracted 2 to 3 times with an equal volume of ethyl acetate, the ethyl acetate layers were combined, washed with saturated aqueous sodium chloride solution, and then t...

Embodiment 3

[0059] The synthesis of embodiment 3 (2S)-2-(4-(pyridine-3-oxymethyl) benzyl) amino-propionamide (Ia-3)

[0060]

[0061] 3.1 Preparation of 4-(pyridine-4-oxymethyl)-benzaldehyde (IV-1c)

[0062] Take a 250mL eggplant-shaped bottle, weigh 1.0g intermediate III-1 (5.0mmol; 1.0equiv), 0.48g 4-hydroxypyridine (5.0mmol; 1.0equiv), 2.1g potassium carbonate (15.0mmol; 3.0equiv) , 0.6g of potassium iodide (3.0mmol; 0.6equiv), and 60mL of acetone were added to the bottle, stirred evenly, then heated to 58°C for reflux reaction for 24h, spotted by thin-layer TLC, and monitored by an ultraviolet analyzer (254nm). Then the reaction solution was filtered and evaporated to dryness, and the resulting residue was redissolved with 2mol / L NaOH aqueous solution and ethyl acetate and added to a separatory funnel. The aqueous phase was extracted 2 to 3 times with an equal volume of ethyl acetate, the ethyl acetate layers were combined, washed with saturated aqueous sodium chloride solution, a...

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PUM

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Abstract

The invention relates to novel alpha-amino amide derivatives and a pharmaceutical use thereof. Specifically, the invention relates to the alpha-amino amide derivatives represented by the structural formula I or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the compounds as active ingredients, and the use of the derivatives or the pharmaceutically acceptable salts thereof for preparation of analgesic drugs.

Description

technical field [0001] The present invention relates to novel α-aminoamide derivatives or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing these compounds as active ingredients, and the use of said derivatives or pharmaceutically acceptable salts for the preparation of analgesic drugs the use of. Background technique [0002] Neuropathic pain is a chronic pain caused by damage or disease of the central or peripheral somatosensory nervous system, mainly manifested as spontaneous pain (persistent pain and paroxysmal pain) and evoked pain (pain sensation). Hypersensitivity and hyperalgesia), characterized by the persistence of pain sensation after the nervous system injury has healed, seriously affecting the quality of daily life of patients. [0003] Neurogenic pain has a wide range of causes, a high incidence rate, and complex pathological mechanisms. At present, there is a lack of specific therapeutic drugs in clinical practice, which has al...

Claims

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Application Information

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IPC IPC(8): C07D213/64C07D213/65C07D213/68C07C237/06A61K31/4409A61K31/4406A61K31/4402A61K31/165A61P25/04A61P29/00
CPCC07C237/06C07D213/64C07D213/65C07D213/68
Inventor 史卫国李浩田樊士勇仲伯华
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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