CN-115252618-B - Application of pyrazoloquinoline derivative and pharmaceutical composition thereof

Abstract

The invention discloses application of a pyrazoloquinoline derivative and a pharmaceutical composition thereof, belongs to the technical field of biological medicines, and particularly relates to application of the pyrazoloquinoline derivative in preparation of a medicament for preventing or treating tuberculosis, wherein the structure of the pyrazoloquinoline derivative is shown as a general formula (I), R 1 is isopropyl or methyl, and R 2 is 4-quinolyl or 5-quinolyl. The invention also discloses a pharmaceutical composition comprising the pyrazoloquinoline derivative applied to the method. The pyrazoloquinoline derivative has good inhibitory activity on mycobacterium tuberculosis, and widens the types of preparing medicaments for treating tuberculosis.

Inventors

• MA XIAOCHI
• WANG CHAO
• HAN XIUYAN

Assignees

• 大连医科大学附属第二医院

Dates

Publication Date

20260505

Application Date

20220805

Claims (1)

1. 1. The application of the pyrazoloquinoline derivative in preparing the medicament for inhibiting the mycobacterium tuberculosis is characterized in that the pyrazoloquinoline derivative has the following structure: 。

Description

Application of pyrazoloquinoline derivative and pharmaceutical composition thereof Technical Field The invention relates to the field of biological medicine, in particular to application of a pyrazoloquinoline derivative in preparation of a medicine for preventing or treating tuberculosis and a pharmaceutical composition thereof. Background Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis (Mycobacterium tuberculosis) infection, can invade various organs of the whole body of a human body, mainly invade the lung, is called pulmonary tuberculosis, and other diseases such as scrofula, bone tuberculosis, renal tuberculosis and the like. Tuberculosis is always the forefront of national class A and B infectious diseases, and the hazard of multi-drug resistant tuberculosis is also increasingly prominent. Currently, commonly used first-line antitubercular drugs include streptomycin, isoniazid, rifampicin, ethambutol, etc., and second-line antitubercular drugs include sodium salicylate, ofloxacin, kanamycin, clarithromycin, etc. However, research shows that the mycobacterium tuberculosis isolated strain in sputum specimens of tuberculosis patients in China has 36.8 percent of any drug resistance rate to 4 first-line anti-tuberculosis drugs, 6.8 percent of multi-drug resistance rate, 24.6 percent of any drug resistance rate to 7 second-line anti-tuberculosis drugs, 2.1 percent of wide drug resistance rate and 42.1 percent of any drug resistance rate to 11 first-line and second-line anti-tuberculosis drugs. It can be seen that in the prior art, serious drug resistance problems are faced to the prevention and treatment of tuberculosis. Therefore, how to provide an active molecule and a candidate drug which can effectively inhibit mycobacterium tuberculosis and have a remarkable inhibition effect on drug-resistant mycobacterium tuberculosis is a technical problem to be solved by the person skilled in the art. Disclosure of Invention The invention aims to provide application of a pyrazoloquinoline derivative and a pharmaceutical composition thereof, so as to solve the problems in the prior art. In order to achieve the above object, the present invention provides the following solutions: The application of a pyrazoloquinoline derivative in the preparation of a medicament for preventing or treating tuberculosis is disclosed, wherein the structure of the pyrazoloquinoline derivative is shown as a general formula (I): Wherein, R 1 is isopropyl or methyl; R 2 is 4-quinolinyl or 5-quinolinyl. Preferably, the general formula (I) has the following structure: Wherein, the compound 1 is described in the literature 1(Ao A,Hao J,Hopkins C R,et al.DMH1,a Novel BMP Small Molecule Inhibitor,Increases Cardiomyocyte Progenitors and Promotes Cardiac Differentiation in Mouse Embryonic Stem Cells[J].Plos One,2012,7.); Compound 2 is described in the literature 2(Mohedas A H,Xing X,Armstrong K A,et al.Development of an ALK2-biased BMP type I receptor kinase inhibitor.[J].Acs Chemical Biology,2012,8(6):1291-1302.) Preferably, the tuberculosis comprises one or more of pulmonary tuberculosis, bone tuberculosis, lymphoid tuberculosis and renal tuberculosis. A pharmaceutical composition comprises a pyrazolyl quinoline derivative in the application. Preferably, the pharmaceutical composition dosage form comprises a tablet, a capsule, a granule or an injection. The invention discloses application of a pyrazoloquinoline derivative and a pharmaceutical composition thereof, wherein the pyrazoloquinoline derivative not only has remarkable inhibition effect on drug-sensitive mycobacterium tuberculosis, but also has strong inhibition effect on clinical multi-drug resistant strains. Therefore, the pyrazoloquinoline derivative provides a candidate medicament for treating tuberculosis, especially drug-resistant tuberculosis. Drawings In order to more clearly illustrate the embodiments of the present invention or the technical solutions of the prior art, the drawings that are needed in the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art. FIG. 1 is a 1 H NMR spectrum of compound 1 in example 1; FIG. 2 is a 13 C NMR spectrum of compound 1 in example 1; FIG. 3 is an HR-MS spectrum of compound 1 of example 1; FIG. 4 is a 1 H NMR spectrum of compound 2 in example 2; FIG. 5 is a 13 C NMR chart of compound 2 in example 2; FIG. 6 is an HR-MS spectrum of compound 2 of example 2; FIG. 7 is the effect of compound 1 on the growth curve of Mycobacterium tuberculosis H37Ra in example 4; FIG. 8 is the effect of compound 2 on the growth curve of Mycobacterium tuberculosis H37Ra in example 4; FIG. 9 is a chart showing that Compound 1 inhibits Mycobacterium tuberculosis H37Ra from infecting macrophage RAW26