EP-4574813-B1 - COMPOUND HAVING BROAD-SPECTRUM ANTIBACTERIAL ACTIVITY AND ANTIBACTERIAL COMPOSITION THEREOF

Inventors

• SHEN, JIANZHONG
• LIU, DEJUN
• ZHU, KUI
• LI, XIAOYU
• ZHOU, Kaixiang
• MAO, CHANGSI
• CAI, YAWEI
• KANG, JIJUN
• WU, Congming
• CAO, XINGYUAN

Dates

Publication Date

20260513

Application Date

20240126

Claims (4)

1. A compound, having a structure as shown in the following compound BAB159:
2. A composition, comprising the compound BAB159 of claim 1 and polymyxin E as active ingredients; wherein a concentration ratio of BAB159 to polymyxin E is 1-3:1-3.
3. The compound according to claim 1 or the composition according to claim 2 for use in anti-bacterial and/or anti-fungal treatment.
4. The compound or the composition for use according to claim 3, wherein the bacteria include at least one selected from Staphylococcus, Clostridium perfringens, Enterococcus, Bacillus, Streptococcus, Haemophilus, and Mycobacterium smegmatis; and the fungi include at least one selected from Candida, Aspergillus niger, Aspergillus flavus, and Trichophyton.

Description

FIELD OF INVENTION The present invention belongs to the field of antibacterial compound technology, and specifically relates to a compound, a composition, and the compound or the composition for medical use. BACKGROUND OF THE INVENTION With the widespread use of antibiotics, resistance of pathogenic bacteria has become increasingly severe, and bacterial infections, especially those caused by multidrug-resistant bacteria, are facing a situation where no drugs are available. Clostridium perfringens has shown high resistance rates to many antibiotics, such as lincomycin (76.9%), doxycycline (69.2%), tilmicosin (65.4%), and tiamulin (50.0%), with some MIC values reaching 128 µg/mL or even higher. According to research, if left uncontrolled, the number of deaths caused by drug resistance is expected to reach 10 million by 2050. In response to the serious public health threat posed by bacterial resistance, the World Health Organization (WHO) and the US Food and Drug Administration (FDA) have successively released lists of bacteria in urgent need of novel antibiotics (WHO, 2017; FDA, 2017), demonstrating the urgency of developing novel antibiotics. The development of "super antibiotics" capable of combating drug-resistant bacteria has become a rigid requirement for medical development. However, due to the limited variety of natural product structures and the decreasing frequency of discovery, the development of novel antibiotics from natural sources has become increasingly difficult. At the same time, due to the shorter treatment cycle of antibiotics compared to drugs for hypertension, diabetes, leukemia and other drugs, the development investment and income are relatively low, and the pharmaceutical companies have insufficient development incentives for novel antibiotics. In the past 50 years, only one new type of antibacterial drug from natural sources, daptomycin, has been put into clinical use. At present, the artificial design and modification of compounds that may have antibacterial potential is an important means of discovering novel antibacterial compounds, which has received widespread attention in recent years. Benzoyl aniline derivatives are widely used, which have a backbone based on salicylic acid and are bound to aniline derivatives with aromatic rings through amide bonds. They have various biological activities such as weed control, insecticidal, antibacterial, and anticancer. Previous studies have modified the substituents of benzoyl aniline compounds while obtaining some compounds with antibacterial activity against Gram positive bacteria (Bakker et al, J Am Chem Soc, 2023, 145, 1136). Upon comparison, it can be found that the compounds provided by Bakker et al (2023) are mostly heterocyclic structures, and the 12 compounds provided by Bakker et al (2023) have the lowest MIC of 6.25 µg/mL against MRSA, which is not enough to meet the current practical needs. After searching, as of January 2023, there are two application patents based on benzoyl aniline as the parent nucleus structure. CN1958565A proposes a novel snail killing drug; CN102697760A proposes the application of niclosamide or its salts in the preparation of drugs for the prevention and treatment of pulmonary fibrosis. However, no such compounds have been reported as spectral antibacterial drugs, especially against bacteria and their composition. LAL JHAJAN ET AL: "Bio-evaluation of fluoro and trifluoromethylsubstituted salicylanilides against multidrug-resistant S. aureus", MEDICINAL CHEMISTRY RESEARCH, BIRKHAEUSER, BOSTON, US, vol. 30, no. 12, 27 October 2021 (2021-10-27), pages 2301-2315, discloses many fluoro and trifluoromethylsubstituted salicylanilide derivatives in the prior art. LI J ET AL: "Evaluation of colistin as an agent against multi-resistant Gram negative bacteria", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, ELSEVIER, AMSTERDAM, NL, vol. 25, no. 1, 1 January 2005 (2005-01-01), pages 11-25, discloses colistin (polymyxin E) as an agent againts multi-resistant Gram negative bacteria. SUMMARY OF THE PRESENT INVENTION The invention is set out in the appended set of claims. The description may encompass subject-matter extending beyond the scope of the claims. However the scope of the invention and of protection is solely defined by theappended claims. In particular, the scope of protection does not include any method of therapeutic treatment of the human or animal body, even if such subject-matter is disclosed or implied herein. The references to methods of treatment in the subsequent paragraphs of this description are to be interpreted as references to the compounds of the present invention, pharmaceutical composition and medicaments disclosed herein for use in those methods. To fill the gap in the application of compounds with benzoyl aniline as the parent nucleus structure in antibacterial fields, and to propose a fully synthesized benzoyl aniline compound with independent intellectual property rights for antibacterial