A cyclic peptide compound and application thereof in the field of antibacterial

Abstract

The application belongs to the technical field of medicine, and particularly relates to a cyclic peptide compound and application thereof in the field of antibiosis. The application discloses a cyclic peptide compound, the structure of which is shown as formula I. The preliminary experiment verifies that the compound has good effects of resisting Acinetobacter baumannii, and has wide application prospects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a cyclic peptide compound and its application in the field of antibacterial agents. Background Technology

[0002] Acinetobacter baumannii (Ab) is a non-fermenting Gram-negative bacillus that can cause a variety of infectious diseases, including respiratory tract infections, urinary tract infections, bacteremia, wound infections, meningitis, and ventilator-associated pneumonia. Due to its strong adhesion and transmissibility, Ab exhibits widespread resistance to mainstream drugs, including imipenem, meropenem, and cefoperazone-sulbactam, through multiple resistance mechanisms such as carbapenemase production, altered drug targets, loss of outer membrane porins, and active efflux pumps. Simultaneously, its resistance to last-resort treatments such as polymyxins and tigecycline is also significantly increasing, resulting in extremely limited clinical treatment options. Therefore, there is an urgent need to develop novel antibiotics against Acinetobacter baumannii infections.

[0003] In January 2024, researchers from Roche Pharmaceuticals and Harvard University published two articles in the same issue of Nature, reporting the development of a novel antibiotic, Zosurabalpin (Formula II), as a clinical candidate drug with a minimum inhibitory concentration (MIC) of ≤0.06~0.5 μg / mL against Acinetobacter baumannii (Ab). This antibiotic is a tethered macrocyclic peptide composed of a small aromatic ring and a tripeptide, exhibiting high selectivity and excellent broad-spectrum activity against 129 clinical isolates, including Ab and fully drug-resistant Acinetobacter baumannii. This novel antibiotic targets the lipopolysaccharide transporter (Lpt), using hydrogen bonds between amino acid residues in the tripeptide and the LptB2FG protein. This inhibits the efflux of endotoxin lipopolysaccharide synthesized by Ab, leading to excessively high intracellular lipopolysaccharide concentrations, causing Ab poisoning and death, and effectively treating Ab infection. It has now entered Phase I clinical trials.

[0004]

[0005] This application builds upon Zosurabalpin to further investigate a compound with superior antibacterial effects. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a cyclic peptide compound and its application in the field of antibacterial.

[0007] To solve the above problems, the technical solution adopted by the present invention is as follows:

[0008] Technical Topic 1

[0009] A cyclic peptide compound as shown in Formula I, or a pharmaceutical salt thereof:

[0010] .

[0011] Technical Theme Two

[0012] A pharmaceutical composition comprising a cyclic peptide compound or a pharmaceutically acceptable salt thereof as described in Technical Subject 1.

[0013] As a further improvement of the present invention, the pharmaceutical composition further includes one or more pharmaceutically acceptable carriers or excipients.

[0014] As used herein, “pharmaceutically acceptable carriers or excipients” include: diluents, fillers, binders, disintegrants, lubricants, flow aids, granulators, coating agents, wetting agents, solvents, co-solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, taste masking agents, colorants, anti-caking agents, humectants, chelating agents, plasticizers, thickeners, antioxidants, preservatives, stabilizers, surfactants, and buffers. Those skilled in the art will understand that some pharmaceutically acceptable excipients may be used for more than one function and for alternative functions, depending on the amount of said excipient present in the formulation and what other ingredients are present in the formulation.

[0015] For example, when intended for oral administration, it can be formulated into oral preparations such as tablets (including regular tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, and orally disintegrating tablets), capsules (including hard capsules, soft capsules, and enteric-coated capsules), granules, and pills, containing fillers (e.g., sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, and sodium carboxymethyl cellulose); Arabica... Gum; dextran; silicate derivatives such as magnesium aluminum metasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate, etc.), binders (e.g., gelatin, polyvinylpyrrolidone, and polyethylene glycol), disintegrants (e.g., cellulose derivatives such as sodium carboxymethyl cellulose and polyvinylpyrrolidone), lubricants (e.g., talc, calcium stearate, magnesium stearate, cetyl, boric acid, sodium benzoate, leucine), stabilizers (methylparaben, propylparaben, etc.), flavoring agents (e.g., commonly used sweeteners, acidulants, and flavorings, etc.).

[0016] When used parenterally, the drug can be formulated as an injectable preparation, including sterile powder for injection and solvent for injection. The carrier or excipients used may include sterile water, Ringer's solution, and isotonic sodium chloride solution. Appropriate excipients such as antioxidants, buffers, antibacterial agents, solubilizers, co-solvents, pH adjusters, and osmotic pressure regulators may be added depending on the properties of the drug. Solubilizers or co-solvents may include poloxamer, lecithin, hydroxypropyl-β-cyclodextrin, etc.; pH adjusters may include phosphates, acetates, hydrochloric acid, sodium hydroxide, etc.; and osmotic pressure regulators may include sodium chloride, mannitol, glucose, phosphates, acetates, etc. If preparing a lyophilized powder for injection, mannitol, glucose, etc., may also be added as a support agent. When used rectally, the drug can be formulated as suppositories, etc.

[0017] When intended for pulmonary administration, the drug may be formulated as an inhaler or spray, etc. Numerous resources available to those skilled in the art describe pharmaceutically acceptable excipients and can be used to select appropriate pharmaceutically acceptable excipients, such as books like *Remington's Complete Pharmacy*, *Chinese Pharmaceutical Yearbook*, and *Pharmaceutics*.

[0018] The compounds of this invention and their pharmaceutically acceptable salts can be formulated into conventional formulations, as well as sustained-release formulations, controlled-release formulations, targeted formulations, and various microparticle delivery systems.

[0019] Technical Theme 3

[0020] The use of a cyclic peptide compound as described in Technical Subject 1 in the preparation of antibacterial drugs.

[0021] As a further improvement of the present invention, the antibacterial drug is a drug that inhibits Acinetobacter baumannii.

[0022] As a further improvement of the present invention, the antibacterial drug is used to treat infections and related diseases caused by Acinetobacter baumannii.

[0023] As a further improvement of the present invention, the infections and related diseases caused by Acinetobacter baumannii are one or more of the following: bacteremia, pneumonia, meningitis, urinary tract infection, and wound infection caused by Acinetobacter baumannii.

[0024] The beneficial effects of adopting the above technical solution are as follows:

[0025] This invention provides a cyclic peptide compound with antibacterial effects. Preliminary experimental verification shows that this compound has a good effect against Acinetobacter baumannii and has broad application prospects. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the present invention clearer, the invention will be described clearly and completely below in conjunction with specific embodiments.

[0027] Synthesis of Intermediate 1 in Example 1

[0028]

[0029] Step 1: Synthesis of methyl 2-(3-bromo-2-formyl-phenyl)thiopyridine-3-carboxylic acid ester

[0030] Potassium tert-butoxide (20.45 g, 182.5 mmol) was added to a solution of 2-bromo-6-fluorobenzaldehyde (18.5.0 g, 91 mmol) in N,N-dimethylformamide (185 mL) under stirring. The reaction mixture was stirred at 25 °C for 30 min. Then, 2-mercaptonicotinic acid (15.55 g, 100 mmol) was added, and the reaction mixture was stirred at 80 °C for 4 h. After cooling to room temperature, potassium carbonate (75.5 g, 547 mmol) was added, followed by iodomethane (38.8 g, 273.5 mmol). After 16 h, the reaction mixture was partitioned between ethyl acetate and water. The separated organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated under reduced pressure. Chromatographic treatment yielded methyl 2-(3-bromo-2-formyl-phenyl)thiopyridine-3-carboxylic acid (10.5 g, 32.8%). Yellow solid, MS: 351.9 [M + H] + .

[0031] Step 2: Synthesis of 2-[3-bromo-2-[(E)-tert-butylsulfinyliminomethyl]phenyl]thiopyridine-3-carboxylic acid ethyl ester

[0032] To a solution of methyl 2-(3-bromo-2-carboxyyl-phenyl)thioalkylpyridine-3-carboxylate (10.5 g, 29.8 mmol) in tetrahydrofuran (105 mL) under stirring, 2-methyl-2-propanesulfinamide (3.61 g, 29.8 mmol) and titanium ethoxide (28.8 g, 149.4 mmol) were added. The reaction mixture was heated at 70 °C for 4 hours. After cooling, the reaction mixture was treated with brine and then filtered through diatomaceous earth to remove insoluble matter. The filtrate was extracted with ethyl acetate, the separated organic layer was washed with water, dried over sodium sulfate, and evaporated under reduced pressure to give ethyl 2-[3-bromo-2-[(E)-tert-butylsulfinyliminomethyl]phenyl]thiopyridine-3-carboxylate (10.5 g, 78%) as a yellow gel.

[0033] Step 3: Synthesis of N-[[2-bromo-6-[[3-(hydroxymethyl)-2-pyridyl]thio]phenyl]methyl]-2-methyl-propane-2-sulfinamide

[0034] A solution of lithium aluminate in tetrahydrofuran (2.5 M, 20 mL, 50 mmol) was added to a stirred solution of ethyl 2-[3-bromo-2-[(E)-tert-butylsulfinyliminomethyl]phenyl]thiopyridine-3-carboxylate (10.5 g, 23.1 mmol) in tetrahydrofuran (110 mL). The reaction mixture was stirred at 0 °C for 1 hour, and then a saturated aqueous sodium sulfate solution was added. The reaction mixture was extracted with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, filtered, evaporated, and chromatographically treated to give N-[[2-bromo-6-[[3-(hydroxymethyl)-2-pyridinyl]thio]phenyl]methyl]-2-methyl-propane-2-sulfinamide (7.6 g, 76.9%) as a yellow semi-solid.

[0035] Step 4: Synthesis of [2-[2-(aminomethyl)-3-bromo-phenyl]thio-3-pyridyl]methanol hydrochloride

[0036] At room temperature, a solution of hydrogen chloride (4M 1,4-dioxane solution, 8.89 mL, 35.5 mmol) was added to a stirred solution of N-[[2-bromo-6-[[3-(hydroxymethyl)-2-pyridyl]thio]phenyl]methyl]-2-methyl-propane-2-sulfinamide (7.6 g, 17.8 mmol) in tetrahydrofuran (75 mL) and methanol (1.5 mL). After 2 hours, the reaction mixture was concentrated to give [2-[2-(aminomethyl)-3-bromo-phenyl]thio-3-pyridyl]methanol hydrochloride (5.54 g, 86%), which is a grayish-white solid.

[0037] Step 5: Synthesis of N-[[2-bromo-6-[[3-(hydroxymethyl)-2-pyridyl]thio]phenyl]methyl]carbamic acid 9H-fluorene-9-ylmethyl ester

[0038] At room temperature, a stirred suspension of [2-[2-(aminomethyl)-3-bromo-phenyl]thio-3-pyridyl]methanol hydrochloride (5.54 g, 15.3 mmol) in 20 mL of 5% sodium bicarbonate aqueous solution was added to 1,4-dioxane (20 mL) containing (fluorenylmethoxycarbonyl)hydroxysuccinimide ester (6.3 g, 18.5 mmol). After 15 hours, the reaction mixture was partitioned between water and a dichloromethane / methanol solution at a volume ratio of 9:1. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatographic treatment yielded N-[[2-bromo-6-[[3-(hydroxymethyl)-2-pyridyl]thio]phenyl]methyl]carbamate 9H-fluoren-9-ylmethyl ester (3.58 g, 42.8% yield) as a grayish-white solid.

[0039] Step 6: Synthesis of N-[[2-bromo-6-[(3-formyl-2-pyridyl)thio]phenyl]–methyl]carbamate 9H-fluorene-9-ylmethyl ester]

[0040] At 0 °C, 1,1,1-tris(acetoxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (4.16 g, 9.8 mmol) was added to a solution of N-[[2-bromo-6-[[3-(hydroxymethyl)-2-pyridinyl]thio]phenyl]methyl]carbamate 9H-fluorene-9-ylmethyl ester (3.58 g, 6.6 mmol) in dichloromethane (50 mL). The reaction mixture was then allowed to reach room temperature over 1 hour, and the reaction mixture was partitioned between a saturated sodium bicarbonate aqueous solution and dichloromethane. The organic layer was washed with water and brine, dried with sodium sulfate, filtered, and concentrated. Chromatographic processing yielded intermediate 1, N-[[2-bromo-6-[(3-formyl-2-pyridyl)thio]phenyl]–methyl]carbamate 9H-fluorene-9-ylmethyl ester (2.08 g, 58% yield). It was a grayish-white solid, MS: 545.2 [M]. + H] + .

[0041] Example 2 Intermediate 2: N α -(N 2 -(2-amino-5-((tert-butoxycarbonyl)amino)pentanoyl)-N6-(tert-butoxycarbonyl)lysine)-1-(tert-butoxycarbonyl)-N α Synthesis of -methyltryptophan

[0042]

[0043] 2-Chlorotriphenylmethyl chloride resin (1.05 mmol / g, 100-200 mesh) was used as a solid support. The resin was loaded overnight at room temperature with anhydrous dichloromethane containing the first amino acid (2S)-2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-3-[2-methyl-1-[(2-methylprop-2-yl)oxycarbonyl]indol-3-yl]propionic acid (Fmoc-N-Me-Trp(Boc)-OH, 2 equivalents) and diisopropylethylamine (6 equivalents). After thorough washing with N,N-dimethylformamide and dichloromethane, the 9-fluorenylmethoxycarbonyl protecting group was removed by cleavage in N,N-dimethylformamide at room temperature for 30 min with a mixture of 50% piperidine in dichloromethane / N,N-dimethylformamide (v / v, 1:1). Wash with N,N-dimethylformamide, dichloromethane and methanol.

[0044] The second amino acid (N6-[(1,1-dimethylethoxy)carbonyl]-N2-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-lysine (Fmoc-Lys(Boc)-OH, 2 equivalents)) was coupled overnight at room temperature with 4 equivalents of 2-chloro-1-methylpyridinium iodide as a coupling agent and 6 equivalents of N,N-diisopropylethylamine in dichloromethane / N,N-dimethylformamide (1:1). The resin was thoroughly washed with N,N-dimethylformamide and dichloromethane. The 9-fluorenylmethoxycarbonyl group was cleaved from the dipeptide with a mixture of piperidine / dichloromethane / N,N-dimethylformamide (2:1) for up to 5 minutes, followed by washing with N,N-dimethylformamide and dichloromethane.

[0045] The third amino acid (N5-[(1,1-dimethylethoxy)carbonyl]-N2-[(9H-fluorene-9-ylmethoxy)carbonyl]-L-ornithine (Fmoc-Orn(Boc)-OH, 2 equivalents)) was coupled using 4 equivalents of O-(7-azabenzotriazol-1-yl)-N,N',N'-tetramethylureonium-hexafluorophosphate as a coupling agent and 6 equivalents of diisopropylethylamine. Complete coupling was achieved at room temperature over 2–4 hours. The 9-fluorene-methoxycarbonyl group of the tripeptide was cleaved at room temperature for 2 × 15–20 min with a mixture of 20% piperidine in N,N-dimethylformamide, followed by washing with N,N-dimethylformamide and dichloromethane.

[0046] Example 3 Intermediate 3: Synthesis of tert-butyl 3-(((7S,10S,13S)-17-bromo-10-(4-((tert-butoxycarbonyl)amino)butyl)-7-(3-((tert-butoxycarbonyl)amino)propyl)-12-methyl-8,11,14-trioxo-5,6,7,8,9,10,11,12,13,14,15,16-dodecylhydrobenzo[b]pyrido[3,2-p][1]thia[5,8,11,14]tetraazacycloheptadecanoyl)methyl)-1H-indole-1-carboxylic acid

[0047]

[0048] Step 1: Reductive amination

[0049] The tripeptide-containing resin prepared in Example 2 was washed with dichloromethane. Intermediate 1 was dissolved in a mixture of 1-methyl-2-pyrrolidone / trimethyl orthoformate / acetic acid (49.7 / 49.7 / 0.6), and the solution was added to intermediate 2. The mixture was shaken at room temperature for 30 minutes to 3 hours, then 10 equivalents of sodium cyanoborohydride were added, and the reaction mixture was shaken at room temperature overnight.

[0050] The resin was then washed with N,N-dimethylformamide, dichloromethane, methanol / dichloromethane (1:1), and N,N-dimethylformamide. The 9-fluorenylmethoxycarbonyl group on the chain was cleaved with a mixture of 20% piperidine in N,N-dimethylformamide at room temperature for 2 × 15–20 min, followed by washing with N,N-dimethylformamide and dichloromethane.

[0051] Step 2: Crack

[0052] Add 20% hexafluoroisopropanol in dichloromethane as a cracking agent to the resin and stir the mixture at room temperature for 2 hours. Filter the resin and evaporate the solution to dryness. Dissolve the residue in water / acetonitrile and freeze-dry.

[0053] Step 3: Cycloning

[0054] The crude linear compound obtained in step 2 was cyclized by dissolving the powder in N,N-dimethylformamide. 1.2 equivalents of O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylureon hexafluorophosphate and 4 equivalents of diisopropylethylamine were added, and the reaction mixture was stirred at room temperature. The reaction progress was monitored by HPLC. After completion, the reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated. The residue was treated with silica gel chromatography using a heptane-ethyl acetate gradient as eluent. The crude product was given. The crude product was purified by reversed-phase high-performance liquid chromatography (RP-HPLC) using a Phenomenex Gemini-NX5u 110A column (100 × 30 mm) as the stationary phase and a gradient from water (+0.05% trifluoroacetic acid) to acetonitrile as eluent, followed by lyophilization.

[0055] Example 4 Synthesis of target compound WM-3-4

[0056]

[0057] 3-(((7S,10S,13S)-17-bromo-10-(4-((tert-butoxycarbonyl)amino)butyl)-7-(3-((tert-butoxycarbonyl)amino)propyl)-12-methyl-8,11,14-trioxo-5,6,7,8,9,10,11,12,13,14,15,16-dodecylhydrobenzo[b]pyrido[3,2-p][1]thia[5,8,11]

[14] Cycloheptadecin-13-yl)methyl)-1H-indole-1-carboxylic acid tert-butyl ester (intermediate 3; 1.07 g, 0.99 mmol), 4-(methylcarbonyl)phenylboronic acid (337 mg, 1.48 mmol), and sodium carbonate (261 mg, 2.46 mmol) were dissolved in dioxane / water 6:1 (22 mL). The reaction mixture was purged with argon for 2 minutes while the container was sonicated in an ultrasonic bath. Tetra(triphenylphosphine)-palladium(0) (230 mg, 197 μmol) was then added, followed by further degassing for 2 minutes. The tube was then sealed and heated at 120 °C for 30 minutes under microwave irradiation. After cooling, the reaction mixture was partitioned between ethyl acetate and a 1 M sodium carbonate aqueous solution. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and evaporated to give the crude product (0.6 g, light orange foam). The substance was dissolved in methanol, and a 16% sodium hydroxide aqueous solution was added. The mixture was reacted at 40°C for 5 h, then cooled to room temperature. A 35% citric acid aqueous solution was then added and stirred for 5 min. The reaction mixture was partitioned between the aqueous solution and ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The substance was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (10 mL, 148 mmol) at room temperature. After 90 min, the reaction mixture was evaporated under vacuum. The residue was dissolved in water (10 mL), stirred at room temperature for 2 h, and then lyophilized. The residue was dissolved in water / acetonitrile 10:1 and purified by preparative HPLC using a C18 reversed-phase column (Phenomenex Gemini-NX5u110A, 100 × 30 mm) with a gradient of water (+0.05% trifluoroacetic acid) to acetonitrile as eluent. The pure fraction was lyophilized to give the target compound as a tetra(trifluoroacetic acid) salt (0.15 g, 12.5%). White lyophilized powder, MS: 867.4 [M+H]+, HPLC purity: 98.8%

[0058] 1 H NMR (600 MHz, Methanol- d 4) δ 8.44 (dd, J= 4.8, 1.7 Hz, 1H), 8.15 –8.10 (m, 2H), 7.87 – 7.76 (m, 5H), 7.68 (d, J = 7.9 Hz, 1H), 7.58 – 7.53 (m,2H), 7.46 (d, J = 6.6 Hz, 2H), 7.44 – 7.40 (m, 2H), 7.21 – 7.14 (m, 2H), 7.12(t, J = 7.5 Hz, 1H), 4.73 (d, J = 10.8 Hz, 1H), 4.65 (d, J = 13.8 Hz, 1H), 4.58 (d, J = 13.9 Hz, 1H), 4.43 (d, J = 13.8 Hz, 1H), 4.23 (d, J = 13.6 Hz, 1H), 4.06 (s,1H), 3.63 (s, 1H), 3.28 (d, J = 3.8 Hz, 1H), 3.21 (dd, J = 15.1, 11.1 Hz, 1H),2.65 – 2.54 (m, 2H), 1.92 (d, J = 11.7 Hz, 1H), 1.88 – 1.79 (m, 1H), 1.73 (t, J =5.7 Hz, 1H), 1.63 (dd, J = 11.6, 6.2 Hz, 1H), 1.29 (d, J = 5.6 Hz, 1H), 1.10 (td, J = 11.9, 10.6, 5.1 Hz, 2H), 1.02 – 0.84(m, 1H), 0.10 -0.00 (m, 1H).

[0059] Example 1: Determination of the in vitro antibacterial activity of compound WM-3-4 against Acinetobacter baumannii.

[0060] In this example, the growth inhibitory concentrations (IC50) of the compound against 14 strains, including Acinetobacter baumannii strains ATCC19606, 16-33, and 25-1, were quantitatively determined using 10-point Iso-Sensitest broth medium.

[0061] Prepare 5×10⁻⁶ microtiter plates in 384-well microtiter plates. 5 Iso-Sensitest medium containing 50 μL of compound WM-3-4, Zosurabalpin, or colistin at CFU / ml for different Acinetobacter baumannii species, with a final concentration of 10 to 0.020 μg / mL (in 2-fold dilutions), was used to incubate the microtiter plates at 35 ± 2 °C.

[0062] During the 16-hour period, the optical density at λ = 600 nm was measured every 20 minutes to determine bacterial cell growth.

[0063] During the logarithmic growth of bacterial cells, inhibition of 50% (IC50) was measured. 50 The minimum concentration required for growth inhibition is determined, and the growth inhibition concentration IC is calculated. 50 .

[0064] Test results showed that the specific compound WM-3-4 of this invention exhibited excellent specific antibacterial activity against 14 strains of Acinetobacter baumannii, including the standard strain ATCC 19606. This activity was significantly superior to that of colistin and the clinical control drug Zosurabalpin.

[0065]

[0066] Note: CRAB refers to carbapenem-resistant Acinetobacter baumannii.

[0067] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A cyclic peptide compound of Formula I: ###0001### or a pharmaceutically acceptable salt thereof. 。 2. A pharmaceutical composition, characterized by, 2. A pharmaceutical composition comprising the cyclic peptide compound of claim 1 or a pharmaceutically acceptable salt thereof.

3. The pharmaceutical composition of claim 2, wherein, 3. The pharmaceutical composition of claim 2, further comprising one or more pharmaceutically acceptable carriers.

4. Use of the cyclic peptide compound according to claim 1 for the preparation of an antibacterial medicament, characterized in that, 4. The pharmaceutical composition of claim 2, wherein the antibacterial agent is an agent that inhibits Acinetobacter baumannii.

5. Use according to claim 4, characterized in that, 5. The pharmaceutical composition of claim 2, wherein the antibacterial agent is used to treat an infection caused by Acinetobacter baumannii.

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