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Application of 2-arylimidazo[1,2-alpha]pyridine-3-acetamide derivative to prepare medicines for controlling PTSD

A technology of acetamide and methylimidazole, which is applied in the field of preparation of drugs for the prevention and treatment of PTSD, can solve the problem that there is no literature report on the effect of TSPO ligand on anti-PTSD

Active Publication Date: 2014-07-23
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

No clear relationship between TSPO and PTSD has been systematically found; there is no literature reporting the role of TSPO ligands against PTSD

Method used

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  • Application of 2-arylimidazo[1,2-alpha]pyridine-3-acetamide derivative to prepare medicines for controlling PTSD
  • Application of 2-arylimidazo[1,2-alpha]pyridine-3-acetamide derivative to prepare medicines for controlling PTSD
  • Application of 2-arylimidazo[1,2-alpha]pyridine-3-acetamide derivative to prepare medicines for controlling PTSD

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Experiment on the behavioral effect of YL-IPA08 on the mouse model of post-traumatic stress disorder (transient electric shock model)

[0051] 1. Experimental materials:

[0052] 1. Experimental animals:

[0053] ICR mice, male, SPF grade, with an initial weight of 18-20 g, were purchased from Weitong Lihua Laboratory Animal Co., Ltd., license: SCXK (Beijing) 2007-0001.

[0054] 2. Test sample:

[0055] YL-IPA08 (namely compound 8, synthesized by the Institute of Toxicology, Academy of Military Medical Sciences, the preparation method is shown in the Chinese patent application with publication number CN102295642A; purity 99%); positive drug sertraline (Ser, purchased from Sigma).

[0056] 2. Experimental method:

[0057] Behavioral effects of YL-IPA08 on a mouse model of post-traumatic stress disorder (brief shock model).

[0058] 1. Environmental adaptation:

[0059] Within 7 days of acclimatization, the mice were gently grasped for 3 minutes a day, in ...

Embodiment 2

[0089] Example 2: Experiment on the behavioral effect of YL-IPA08 on rat model of post-traumatic stress disorder (time dependent sensitization, TDS) time-dependent sensitization model

[0090] 1. Experimental materials:

[0091] 1. Experimental animals:

[0092] SD rats, male, SPF grade, with an initial weight of 180-200g, were purchased from Weitong Lihua Laboratory Animal Co., Ltd., license: SCXK (Beijing) 2007-0001.

[0093] 2. Test sample:

[0094] YL-IPA08 (namely compound 8, synthesized by the Institute of Toxicology, Academy of Military Medical Sciences, the preparation method is shown in the Chinese patent application with publication number CN102295642A; purity 99%); positive drug sertraline (Ser, purchased from Sigma).

[0095] 2. Experimental method:

[0096] Behavioral effects of YL-IPA08 on a rat model of post-traumatic stress disorder (time dependent sensitization, TDS).

[0097] 1. Environmental adaptation:

[0098] Within 7 days of adapting to the enviro...

Embodiment 3

[0131] Example 3: Pharmacodynamic study of PK11195 antagonizing YL-IPA08 in the rat Fear extinction model

[0132] 1. The purpose of the experiment:

[0133] Whether the anti-PTSD effect of YL-IPA08 is mediated by TSPO was investigated by whether the TSPO-specific blocker PK11195 could antagonize the anti-PTSD effect of YL-IPA08 in the rat Fear extinction model.

[0134] 2. Experimental materials:

[0135] 1. Experimental animals:

[0136] SD rat: male, SPF grade.

[0137] 2. Instrument:

[0138] Conditioned fear box (Med associates Inc Video Freeze SOF-843., USA).

[0139] 3. Medication and treatment:

[0140] Sertraline (Sertraline, Ser) and PK11195 were purchased from Sigma-Aldrich (St Louis, MO, U.S.A.); YL-IPA08 (namely, compound 8, was synthesized by the Institute of Toxicology and Drugs, Academy of Military Medical Sciences, and the preparation method is shown in Publication No. CN102295642A Chinese patent application, purity 99.96%, batch number 100916). Excep...

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Abstract

The invention belongs to the field of medicinal chemical engineering, and relates to application of 2-arylimidazo[1,2-alpha]pyridine-3-acetamide derivatives to prepare medicines for controlling PTSD (posttraumatic stress disorder). Specifically, the invention relates to application of a compound shown as a formula I and pharmaceutically salts thereof to prepare medicines for controlling and / or treating and / or auxiliarily treating PTSD, wherein the compound and the pharmaceutically salts thereof are used as TSPO (translocator protein) ligands. The TSPO ligands such as the compounds shown as the formula I and the pharmaceutically salts are capable of effectively preventing and / or treating and / or auxiliarily treating PTSD, and can be used to prevent medicines for controlling and / or treating and / or auxiliarily treating PTSD.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to the use of 2-arylimidazo[1,2-α]pyridine-3-acetamide derivatives in the preparation of medicines for preventing and treating PTSD. Background technique [0002] In recent years, with the continuous occurrence of emergencies such as severe natural disasters, epidemics of major infectious diseases, and military conflicts around the world, post-traumatic stress disorder (PTSD) has become a major disease that endangers human health. [0003] PTSD refers to the delayed appearance and long-term persistence of mental disorders in individuals after encountering unusual threats or disasters. The clinical manifestations mainly include pathological recurrence, persistent increased vigilance and avoidance. The diagnostic criteria, pathogenesis, and animal models of PTSD are different from those of depression and anxiety disorders. For clinical diagnostic criteria of PTSD, please r...

Claims

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Application Information

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IPC IPC(8): A61K31/437A61K31/444A61K31/5377A61P25/18A61P25/22A61P25/24
Inventor 李云峰杨日芳张黎明仇志坤赵楠李永臻陈红霞张有志张城王真真袁莉王好山薛瑞恽榴红
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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