CN-120136762-B - Application of diamidino-containing compound and pharmaceutically-acceptable salt in antifungal

Abstract

The invention provides an application of a compound containing diamidino and pharmaceutically usable salts in antifungal, and belongs to the technical field of medicines. The diamidino-containing compounds of the invention have the structure R 1 and R 2 shown in formula I are independently selected from hydrogen, substituted or unsubstituted C 1‑12 alkyl or C 3‑12 cycloalkyl, or R 1 and R 2 form a substituted or unsubstituted 3-6 membered ring with N, R 3 is independently selected from hydrogen, substituted or unsubstituted alkyl, or R 2 and R 3 are linked to amidino to form a substituted or unsubstituted 5-7 membered ring, R 1 is independently selected from hydrogen, substituted or unsubstituted alkyl, R is independently selected from hydrogen, halogen, haloalkyl or alkoxy, X and Y are independently selected from C or N, Q is independently selected from oxygen, amino, alkylamino, alkynyl, alkoxy or the absence of a Q group, i.e. the two aromatic rings are directly linked. The diamidino-containing compound has good candida albicans activity and therapeutic index, can be used for clinically resisting candida albicans and solves the problem of fungal drug resistance.

Inventors

• CHEN XIAOFANG
• LI YAN
• Bian Cong
• ZHENG XIAO
• LIU YONGHUA
• ZHANG JING
• FAN TIANYUN
• HU LAIXING

Assignees

• 中国医学科学院医药生物技术研究所

Dates

Publication Date

20260512

Application Date

20250312

Claims (1)

1. 1. Use of a diamidino-containing compound shown below and a pharmaceutically acceptable salt thereof for the preparation of a medicament against candida albicans: 。

Description

Application of diamidino-containing compound and pharmaceutically-acceptable salt in antifungal Technical Field The invention relates to the technical field of medicines, in particular to application of a diamidino-containing compound and pharmaceutically usable salt in antifungal. Background In recent years, the incidence of fungal infections has been continuously rising. The 2017 report shows that yearly mold and yeast (e.g., aspergillus and candida) infections cause over 150 tens of thousands of deaths worldwide. A recent study in the journal of lancet-infectious disease has found that the annual global death associated with fungal infections is severely underestimated, about two times 375 tens of thousands of previously estimated, with about 260 tens of thousands (68%) of deaths directly caused by fungal infections. Many fungi are resistant to commonly used drugs and clinically available drugs are very limited. The clinical medicines for treating the antifungal diseases mainly comprise 3 major classes of polyenes, triazoles and echinocandins, and the main dosage forms comprise oral medicines, external medicines and intravenous medicines. The polyene compound is a macrolide organic molecule, and the medicines have strong antifungal activity and wide antibacterial spectrum, and representative medicines commonly used clinically are nystatin (nystation) and amphotericin B (amphotericin B, amB). Triazole is the most widely used antifungal medicine at present, mainly comprising fluconazole, itraconazole, voriconazole and the like, and is clinically used for treating candidiasis, cryptococcosis, coccidioidomycosis and the like. The echinocandin antifungal drugs on the market in the 21 st century are natural or semisynthetic lipopeptides, and are active in the markets at home and abroad at present, and the main products are caspofungin, micafungin and anidulafungin. With the wide clinical application, candida albicans has the drug resistance of different degrees, and the clinical application of echinocandins and triazole or polyene drugs in combination is used for treating invasive candida infection. With prolonged abuse of drugs and unnecessary exposure to drugs, fungal resistance to these drugs is increasing, making clinical patient treatment options limited, an increasingly serious challenge to clinicians and patients worldwide. Therefore, the discovery of new targets and new structures of antifungal agents has become an urgent need. Disclosure of Invention In view of the above, the present invention provides a compound containing diamidino, pharmaceutically acceptable salts and uses thereof, which are antifungal drug candidates of new structures, and solve the problem of fungal resistance caused by drug abuse with few choices of antifungal drugs. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides application of a compound containing diamidino and pharmaceutically acceptable salts in antifungal, wherein the compound has a structural formula shown in a formula I: Preferably, R 1 and R 2 are independently selected from hydrogen, substituted or unsubstituted C 1-12 straight chain alkyl, C 3-12 branched alkyl or C 3-12 cycloalkyl. Preferably, R 1 and R 2 together with the N to which they are attached form a substituted or unsubstituted 3-6 membered ring, and R 3 is independently selected from hydrogen, substituted or unsubstituted alkyl. Preferably, R 2 and R 3 are linked to form a substituted or unsubstituted 5-7 membered ring with the amidino group, and R 1 is independently selected from hydrogen, substituted or unsubstituted alkyl. Preferably, R is independently selected from hydrogen, halogen, haloalkyl or alkoxy, X and Y are independently selected from C or N, Q is independently selected from oxygen, amine groups, alkylamino groups, alkynyl groups, alkoxy groups or the absence of a Q group, and the two aromatic rings are directly connected. The invention also provides application of the diamidino-containing compound and pharmaceutically-acceptable salts in antifungal, wherein the compound has a structural formula shown in a formula II: Preferably, R 1 and R 2 are independently selected from hydrogen, substituted or unsubstituted C 1-12 straight chain alkyl, C 3-12 branched alkyl or C 3-12 cycloalkyl. Preferably, R 1 and R 2 together with the N to which they are attached constitute a substituted or unsubstituted 3-6 membered ring. Preferably, R 2 and R 3 are linked to form a substituted or unsubstituted 5-7 membered ring with the amidino group, and R 1 is independently selected from hydrogen, substituted or unsubstituted alkyl. Preferably, R 3 is independently selected from hydrogen, substituted or unsubstituted alkyl. The specific synthetic process of the compounds shown in the formula I and the formula II can be described as follows: In the above-mentioned synthetic route, the reaction product, 4-Methyl-3-nitro acetonitrile, adding