阅读说明：本技术 噻唑烷二酮类化合物在制备抗腺病毒药物中的应用 (Application of thiazolidinedione compound in preparation of anti-adenovirus medicament ) 是由 杨静 王升启 王晓龙 于 2018-08-27 设计创作，主要内容包括：本发明提供了5-{4-[2-(甲基-2-吡啶氨基)乙氧基]苄基}-2,4-噻唑烷二酮或其药学上可接受的盐、溶剂化物的一种药物新用途,即,5-{4-[2-(甲基-2-吡啶氨基)乙氧基]苄基}-2,4-噻唑烷二酮或其药学上可接受的盐、溶剂化物在制备抗腺病毒药物中的应用。本发明采用两种检测方法,针对三种血清型病毒,在不同细胞系感染模型下对该目标药物进行了系统的体外抗腺病毒活性评价,均做出了有效性验证,体现出5-{4-[2-(甲基-2-吡啶氨基)乙氧基]苄基}-2,4-噻唑烷二酮良好的抑制腺病毒复制的作用。(The invention provides a new medicinal application of 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or pharmaceutically acceptable salts and solvates thereof, namely, the application of 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or pharmaceutically acceptable salts and solvates thereof in preparing an anti-adenovirus medicament. The invention adopts two detection methods, aiming at three serotype viruses, carries out systematic in-vitro anti-adenovirus activity evaluation on the target drug under different cell line infection models, makes effectiveness verification, and embodies the good effect of inhibiting adenovirus replication of 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione.)

Use of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or pharmaceutically acceptable salts, solvates thereof in the preparation of an anti-adenovirals medicament.

2. Use according to claim 1, characterized in that: the adenovirus is serotype adenovirus Ad5, Ad7 and Ad 55.

3. An anti-adenovirus medicinal preparation is prepared from 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or pharmaceutically acceptable salts and solvates thereof as active ingredients.

4. The pharmaceutical formulation of claim 3, wherein: the pharmaceutical preparation comprises the following components in percentage by mass:

1-2% of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or a pharmaceutically acceptable salt, solvate thereof;

98-99% of medicinal auxiliary materials.

5. The pharmaceutical formulation according to claim 3 or 4, characterized in that: the pharmaceutical preparation can be prepared into various forms of oral preparations, including: capsule, tablet, granule, powder, pill, dripping pill, sustained-release preparation, oral liquid, mixture and syrup.

Technical Field

The invention belongs to the field of medicines, and particularly relates to application of 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione in preparation of an anti-adenoviruses medicine.

Background

5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione is a thiazolidinedione antidiabetic agent, is a highly selective and potent agonist of peroxisome proliferator-activated receptor gamma (PPAR-gamma), and effectively controls blood glucose by increasing insulin sensitivity. There is no official approval for anti-adenoviral drugs in the treatment of adenoviral infections. At present, most of the drugs used for first-line clinical treatment of adenovirus infection are broad-spectrum antiviral drugs, such as ribavirin and ganciclovir, and in addition, the drug cidofovir has a high success rate for treating early-stage adenovirus infection, but has serious side effects such as nephrotoxicity and myelosuppression. Related researches report that various traditional Chinese medicines have anti-adenovirus activity, such as traditional Chinese medicine monomer astragaloside IV, shikonin, resveratrol, compound zedoary turmeric oil spray, compound traditional Chinese medicine nasal spray, antiviral dropping pill, lung-clearing oral liquid, and throat-clearing dropping pill. However, the safety, effectiveness and specificity of the traditional Chinese medicine or western medicine cannot be well guaranteed. Therefore, screening and development of anti-adenovirus drugs are imperative.

Disclosure of Invention

The invention aims to provide a new medicinal application of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or pharmaceutically acceptable salts and solvates thereof.

The new application of the 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or the pharmaceutically acceptable salt and the solvate thereof provided by the invention is the application thereof in preparing the anti-adenovirus drugs.

In the above application, the adenovirus may be serotype adenovirus Ad5, Ad7, Ad 55.

The invention also discloses a pharmaceutical preparation prepared by taking 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or pharmaceutically acceptable salts and solvates thereof as an active ingredient, which belongs to the protection scope of the invention.

The pharmaceutical preparation comprises the following components in percentage by mass:

1-2% of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione or a pharmaceutically acceptable salt, solvate thereof;

98-99% of medicinal auxiliary materials.

The above pharmaceutical preparation can be made into various forms of oral preparations, including: capsule, tablet, granule, powder, pill, dripping pill, sustained-release preparation, oral liquid, mixture and syrup. The medicaments in various dosage forms can be prepared according to the conventional method in the pharmaceutical field.

The invention adopts a plaque method to detect the influence of 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on infectious virus titer in A549 cells infected by three different serotypes of adenovirus Ad5, Ad7 and Ad 55; the q-PCR method is adopted to detect the influence of 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on the copy number of virus DNA in supernatants of another two different cell Hep-2 and Vero cells infected by Ad5, namely, the two detection methods are adopted to systematically evaluate the in vitro anti-adenovirus activity of the target medicament under different cell line infection models aiming at three serotype viruses, validity verification is made, and the 5- {4- [2- (methyl-2-pyridylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione has good effect of inhibiting adenovirus replication.

Drawings

FIG. 1 shows the effect of ten candidate drugs on the A549 cytopathic effect of adenovirus.

FIG. 2 is a graph showing the effect of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on the cytopathic effect of adenovirus A549.

FIG. 3 shows the toxicity of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on three cell lines, A549, Hep-2 and Vero.

FIG. 4 is a graph of the effect of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on adenovirus titer, note: a is against Ad5 infection; b is against Ad7 infection; c is against Ad55 infection.

FIG. 5 is a graph showing the effect of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on the copy number of viral DNA in supernatants of Hep-2 cells infected with adenovirus.

FIG. 6 is a graph of the effect of 5- {4- [2- (methyl-2-pyridinylamino) ethoxy ] benzyl } -2, 4-thiazolidinedione on the copy number of viral DNA in the supernatant of Vero cells infected with adenovirus.

Detailed Description

The present invention will be described below with reference to specific examples, but the present invention is not limited thereto.

The experimental methods used in the following examples are all conventional methods unless otherwise specified; reagents, biomaterials, etc. used in the following examples are commercially available unless otherwise specified.

Material

Viral strains and cell strains

Ad5 was purchased from American type culture Collection ATCC (

VR-5^TM). Ad55 and Ad7 are provided by the center for controlling infectious diseases of the national academy of military medical sciences of the people's liberation force. Human non-small cell lung cancer A549 cells, human laryngeal cancer Hep-2 cells and African green monkey kidney vero cells are cryopreserved in the laboratory.

Experimental drugs and reagents

The experimental drugs were as follows: all available from mce (medchemexpress) in the united states.