WO2023201712A1 - Dérivé de clofoctol, médicament antibactérien, procédé de préparation correspondant et utilisation associée - Google Patents

Dérivé de clofoctol, médicament antibactérien, procédé de préparation correspondant et utilisation associée Download PDF

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WO2023201712A1
WO2023201712A1 PCT/CN2022/088513 CN2022088513W WO2023201712A1 WO 2023201712 A1 WO2023201712 A1 WO 2023201712A1 CN 2022088513 W CN2022088513 W CN 2022088513W WO 2023201712 A1 WO2023201712 A1 WO 2023201712A1
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chlorphenol
derivative
group
atoms
antibacterial
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Chinese (zh)
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林水木
刘寿平
刘家勇
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Guangzhou Medical University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
    • C07C279/12—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

Definitions

  • the present invention relates to the field of antibacterial, in particular to a chlorphenol derivative, an antibacterial drug, a preparation method and application.
  • Gram-negative bacteria have a special outer membrane composed of a lipopolysaccharide layer and membrane phospholipids, making it difficult for most antibacterial drugs to penetrate the bacterial cell outer membrane to exert effective antibacterial activity. Therefore, it is extremely important to develop new antibacterial drugs that can overcome or slow down the development of drug resistance, especially drugs against Gram-negative bacteria.
  • the present invention provides a chlorphenol derivative, which is highly efficient and low-toxic, has a broad antibacterial spectrum, fast sterilization speed, excellent antibacterial activity in vivo, good medicinal properties, and can effectively avoid the development of bacterial resistance.
  • the present invention is realized through the following technical solutions.
  • L 1 is selected from a linear alkyl group having 1 to 10 C atoms or a branched or cyclic alkyl group having 3 to 10 C atoms;
  • R1 is selected from a guanidine group, an amino group, an arginine group, a histidine group, a lysine group or a combination of these groups.
  • L 1 is selected from linear alkyl groups having 1 to 6 C atoms or branched or cyclic alkyl groups having 3 to 6 C atoms.
  • L 1 is selected from linear alkyl groups having 1 to 4 C atoms.
  • R 1 is selected from any one of the following groups:
  • the chlorphenol derivative is selected from the following structures:
  • the present invention also provides a method for preparing the chlorphenol derivative as described above, which includes the following steps:
  • the intermediate B is subjected to a dehydration condensation reaction to prepare the chlorphenol derivative.
  • the temperature of the Williamson synthesis reaction is 60°C to 70°C, and the time is 4h to 5h.
  • the present invention also provides the use of the above-mentioned chlorphenol derivatives in the preparation of antibacterial drugs.
  • the present invention also provides an antibacterial drug, the components of which include the above-mentioned chlorphenol derivatives, salts and pharmaceutically acceptable excipients.
  • the chlorphenol derivative of the present invention has the following beneficial effects:
  • the clofol derivative of the present invention uses clofol as a molecular skeleton, is an amphipathic cationic compound, has a novel membrane-targeted antibacterial mechanism, and broadens the antibacterial spectrum of clofol.
  • the chlorphenol derivatives of the present invention are effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, and Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii.
  • Klebsiella pneumoniae exhibit excellent in vitro and in vivo antibacterial activity, have good water solubility and excellent in vivo pharmacokinetic properties, and exhibit low cytotoxicity and hemolytic activity against mammalian cells.
  • Membrane selection It has high potency and good medicinal properties. This type of antibacterial drugs not only have strong broad-spectrum antibacterial activity, but can also overcome the development of bacterial resistance in laboratory simulated drug resistance studies.
  • Figure 1 shows the drug resistance research provided by the present invention; wherein, A represents the research on the resistance of FT09 and norfloxacin to Staphylococcus aureus ATCC29213, and B represents the research on the resistance of FT09 and amoxicillin to Escherichia coli ATCC25922. ;
  • Figure 2 is a cytotoxicity study provided by the present invention. where A represents the cytotoxicity of chlorphenol on mouse fibroblasts, and B represents the cytotoxicity of FT09 on mouse fibroblasts;
  • Figure 3 shows the effect of compound FT09 provided by the present invention on the integrity of the cell membrane of Staphylococcus aureus ATCC29213;
  • Figure 4 is an in vivo antibacterial activity study provided by the present invention; wherein, A represents the in vivo antibacterial activity study of FT09 and vancomycin against Staphylococcus aureus ATCC29213, and B represents the in vivo antibacterial activity study of FT09 and gatifloxacin against Pseudomonas aeruginosa ATCC9027. Antibacterial activity studies.
  • the elements carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds described in the present invention all include their isotope conditions, and the elements carbon, hydrogen, oxygen involved in the groups and compounds described in the present invention , sulfur or nitrogen are optionally further replaced by one or more of their corresponding isotopes.
  • alkyl refers to a saturated hydrocarbon containing primary (normal) carbon atoms, or secondary carbon atoms, or tertiary carbon atoms, or quaternary carbon atoms, or combinations thereof. Phrases containing this term, for example, "C 1 to C 9 alkyl” refer to alkyl groups containing 1 to 9 carbon atoms, and each occurrence may be independently C 1 alkyl, C 2 alkyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, C 6 alkyl, C 7 alkyl, C 8 alkyl, C 9 alkyl.
  • Suitable examples include, but are not limited to: methyl (Me, -CH 3 ), ethyl (Et, -CH 2 CH 3 ), 1-propyl (n-Pr, n-propyl, -CH 2 CH 2 CH 3 ), 2-propyl (i-Pr, i-propyl, -CH(CH 3 ) 2 ), 1-butyl (n-Bu, n-butyl, -CH 2 CH 2 CH 2 CH 3 ) , 2-methyl-1-propyl (i-Bu, i-butyl, -CH 2 CH (CH 3 ) 2 ), 2-butyl (s-Bu, s-butyl, -CH (CH 3 )CH 2 CH 3 ), 2-methyl-2-propyl (t-Bu, t-butyl, -C(CH 3 ) 3 ), 1-pentyl (n-pentyl, -CH 2 CH 2 CH 2 CH 3 ), 2-pentyl (-CH(CH 3
  • Ammonia refers to a derivative of ammonia having the structural characteristics of the formula -N(X) 2 , where each "X” is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted Cycloalkyl, substituted or unsubstituted heterocyclyl, etc.
  • Non-limiting types of amino groups include -NH 2 , -N(alkyl) 2 , -NH(alkyl), -N(cycloalkyl) 2 , -NH(cycloalkyl), -N(heterocyclyl) 2 , -NH (heterocyclyl), -N (aryl) 2 , -NH (aryl), -N (alkyl) (aryl), -N (alkyl) (heterocyclyl), -N (Cycloalkyl)(heterocyclyl), -N(aryl)(heteroaryl), -N(alkyl)(heteroaryl), etc.
  • the invention provides a chlorphenol derivative, the structure of which is shown in the general formula (1):
  • L 1 is selected from a linear alkyl group having 1 to 10 C atoms or a branched or cyclic alkyl group having 3 to 10 C atoms;
  • R1 is selected from a guanidine group, an amino group, an arginine group, a histidine group, a lysine group or a combination of these groups.
  • L 1 is selected from linear alkyl groups having 1 to 6 C atoms or branched or cyclic alkyl groups having 3 to 6 C atoms. More specifically, L 1 is selected from linear alkyl groups having 1 to 4 C atoms.
  • R 1 is selected from any one of the following groups:
  • chlorphenol derivative is selected from the following structures:
  • chlorphenol derivative is selected from the following structures:
  • connection site between amino acids is the amide bond by default.
  • the present invention also provides a preparation method of the above-mentioned chlorphenol derivative, which includes the following steps:
  • the intermediate B is subjected to a dehydration condensation reaction to prepare a chlorphenol derivative.
  • the temperature of the Williamson synthesis reaction is 60°C to 70°C, and the time is 4h to 5h.
  • the present invention also provides the use of the above-mentioned chlorphenol derivatives in the preparation of antibacterial drugs.
  • the present invention also provides an antibacterial drug, the components of which include the above-mentioned chlorphenol derivatives, salts and pharmaceutically acceptable excipients.
  • This embodiment provides a chlorphenol derivative FT07 and its preparation method.
  • the synthesis route is as follows:
  • HATU '-Tetramethylurea hexafluorophosphate
  • DIPEA N,N-diisopropylethylamine
  • L-arginine methyl ester dihydrochloride 157.3mg, 0.60mmol
  • This embodiment provides a chlorphenol derivative FT09 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT05 (80.0 mg, 0.18 mmol), HATU (168.9 mg, 0.44 mmol), DIPEA (154 ⁇ L, 0.88 mmol) and H-Arg-Arg-Arg-OMe ⁇ 4HCl (129.0 mg, 0.20 mmol) were synthesized according to the method of synthesizing FT07 Using this method, a white solid product FT09 (138.2 mg, 88%) was prepared.
  • This embodiment provides a chlorphenol derivative FT12 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT07 (64.4 mg, 0.11 mmol), HATU (120.9 mg, 0.33 mmol), DIPEA (111 ⁇ L, 0.65 mmol) and H-Arg-Arg-NH 2 ⁇ 3HCl (89.4 mg, 0.20 mmol) were synthesized according to the method for synthesizing FT07 Method, the yellow oily product FT12 (49.7 mg, 51%) was prepared.
  • This embodiment provides a chlorphenol derivative FT37 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT05 (75mg, 0.18mmol), HATU (202.1mg, 0.53mmol), DIPEA (185 ⁇ L, 1.06mmol) and H-Arg-Arg-OMe ⁇ 3HCl (116.4mg, 0.27mmol) were synthesized according to the method of synthesizing FT07,
  • the yellow-white solid product FT37 (103.6 mg, 80%) was prepared.
  • This embodiment provides a chlorphenol derivative FT40 and its preparation method.
  • the specific preparation steps are as follows:
  • This embodiment provides a chlorphenol derivative FT41 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT07 (50.3mg, 0.09mmol), HATU (99.0mg, 0.26mmol), DIPEA (91 ⁇ L, 0.52mmol) and H-Arg-Arg-Arg-OMe ⁇ 4HCl (86.9mg, 0.14mmol) were synthesized according to the method of synthesizing FT07 Using this method, the yellow oily product FT41 (38.6 mg, 42%) was prepared.
  • This embodiment provides a chlorphenol derivative FT42 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT37 (94.6mg, 0.13mmol), HATU (144.1mg, 0.38mmol), DIPEA (132 ⁇ L, 0.76mmol) and H-Arg-Arg-Arg-OMe ⁇ 4HCl (126.5mg, 0.20mmol) were synthesized according to the method of synthesizing FT07 Using this method, the yellow oily product FT42 (40.7 mg, 26%) was prepared.
  • This embodiment provides a chlorphenol derivative FT46 and its preparation method.
  • the preparation process is as follows:
  • reaction solution was stirred and reacted at room temperature for 24 hours. After the reaction is complete, the reaction solution is extracted twice with n-butanol, the organic phase is concentrated, dried, dissolved in dichloromethane (15 mL), and trifluoroacetic acid (3 mL) is added, mixed and stirred for 1 hour, and extracted twice with n-butanol. After several times, the organic phase was concentrated and purified using semi-preparative high-performance liquid phase separation. The product FT46 was prepared as a yellow oil (27.3 mg, 34%).
  • This embodiment provides a chlorphenol derivative FT49 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT05 (71.8 mg, 0.16 mmol), HATU (181.5 mg, 0.48 mmol), DIPEA (166 ⁇ L, 0.95 mmol) and H-Arg-Arg-NH 2 ⁇ 3HCl (104.6 mg, 0.24 mmol) were synthesized according to the method for synthesizing FT07 Method, a white solid product FT49 (86.3 mg, 74%) was prepared.
  • This embodiment provides a chlorphenol derivative FT60 and its preparation method.
  • the synthesis route is as follows:
  • the reactants FT59 (56.3 mg, 0.12 mmol), HATU (115.3 mg, 0.30 mmol), DIPEA (105 ⁇ L, 0.60 mmol) and H-Arg-Arg-Arg-OMe ⁇ 4HCl (90.8 mg, 0.14 mmol) were synthesized according to the method of synthesizing FT07 Using this method, the yellow oily product FT60 (96.4 mg, 76%) was prepared.
  • the antibacterial activity of the synthesized compounds was tested according to the broth dilution method specified by Clinical and Laboratory Standards Institute (CLSI) guidelines. Bacterial cells were inoculated onto Mueller-Hinton agar (MHA) plates and cultured overnight, and the bacterial cell concentration was adjusted to approximately 1 ⁇ 10 6 CFU/mL with PBS for preparation of bacterial suspension. The sample was first dissolved in DMSO/H 2 O to prepare a sample stock solution with a concentration of 1000 ⁇ g/mL (final concentration of DMSO ⁇ 2%), and then the stock solution was diluted with Mueller-Hinton agar (MHB) to an initial concentration of 200 ⁇ g/mL.
  • CCSI Clinical and Laboratory Standards Institute
  • Fresh rabbit red blood cells (RBCs) were centrifuged at 2500 rpm for 3 min and then washed twice with PBS. Rabbit red blood cells were then resuspended in PBS to prepare an 8% (v/v) cell suspension. Samples were first dissolved in DMSO or PBS (final concentration of DMSO ⁇ 0.5%) and then diluted with PBS to prepare two-fold gradient dilutions (400 to 3.125 ⁇ g/mL). Rabbit red blood cell suspension (100 ⁇ L) was mixed with a two-fold gradient dilution of the sample (100 ⁇ L) and added to a sterile 96-well plate.
  • the 96-well plate was incubated at 37°C for 1 hour and centrifuged at 2500 rpm for 5 minutes. Transfer the supernatant (100 ⁇ L) to a new 96-well plate, and use a multifunctional microplate reader to measure the absorbance at 576 nm.
  • the 2% Triton X-100 solution treatment group is used as a positive control, and the PBS or 0.5% DMSO treatment group is used. Used as negative control.
  • the initial MIC values of compound FT09 and norfloxacin against Staphylococcus aureus ATCC29213 and the initial MIC values of FT09 and amoxicillin against E. coli ATCC25922 were obtained by the above MIC determination method. Then take out the bacterial cells in the 96-well plate with a concentration of 0.5 ⁇ MIC to prepare a bacterial suspension (about 1 ⁇ 10 6 CFU/mL) for the next step of MIC value determination. After the sample was incubated at 37°C for 24 hours, the change in MIC value of the sample was measured. The experiment was carried out continuously for 22-23 days.
  • NCTC clone 929 The cytotoxicity of chlorphenol and its derivative FT09 on mouse fibroblasts was evaluated by CCK-8 method.
  • Log-phase mouse fibroblasts (NCTC clone 929) cells were digested with 0.25% trypsin (containing EDTA) for 3 minutes, then pipetted and diluted with RPMI 1640 medium (containing 10% fetal bovine serum FBS) and inoculated into 96 wells. plate (approximately 2 ⁇ 10 4 cells/well), incubate at 37°C for 24 h under a 5% CO 2 atmosphere and then remove the culture medium.
  • RPMI 1640 medium containing 10% fetal bovine serum FBS
  • Chlorphenol and its derivative FT09 were first dissolved in DMSO (final concentration of DMSO ⁇ 0.1%), and then diluted with RPMI 1640 medium (containing 10% fetal bovine serum FBS) to prepare a two-fold gradient dilution (200 to 3.125 ⁇ g/mL). Two-fold gradient dilutions (100 ⁇ L) of the above samples were added to a 96-well plate and incubated with NCTC clone 929 cells for 24 h; finally, a CCK-8 solution with a final concentration of 10 ⁇ L was added to each well and incubated in the incubator for 1.0 h. Then use a microplate reader to measure the absorbance of the solution at 450nm (OD 450 ).
  • mice Female C57BL6 mice (6-8 weeks, average weight 20g) were used in this study.
  • an immunosuppressed mouse model was established for the mouse corneal infection model induced by Staphylococcus aureus ATCC29213, while the corneal infection model induced by Pseudomonas aeruginosa ATCC9027 did not require immunosuppression of the mice.
  • mice Five days before infection, mice were injected intraperitoneally with cyclophosphamide (100 mg/kg) three times.
  • mice Bacterial cells (Staphylococcus aureus ATCC 29213) seeded on Mueller Hinton agar (MHA) plates were suspended with PBS, and the bacterial suspension concentration was adjusted to approximately 5 ⁇ 10 7 CFU/mL for corneal infection.
  • the mice were anesthetized by intraperitoneal injection of 2.5% Avertin (500 mg/kg) anesthetic, and then the cornea of the left eye of the mouse was scratched with a sterile needle, and 15 ⁇ L of bacterial suspension was dropped onto the damaged cornea.
  • mice were randomly divided into three groups (5 mice per group) and compounds (0.5% FT09, 5% glucose solution, 5% vancomycin, or 0.3% gatifloxacin) were topically applied four times daily.
  • mice administered continuously for 3 days. Finally, the mice were euthanized, the injured corneas were collected, and viable bacteria were counted by MHA plate counting. SPSS 22.0 software was used to calculate the P value, and P ⁇ 0.05 was considered to be statistically significant.
  • Compound FT09 shows excellent in vitro antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria, and has very high membrane selectivity and high safety. We further evaluate its use in animals. antibacterial effect.
  • mice were first treated with cyclophosphamide to immunosuppress the mice, and then a mouse corneal infection model induced by Staphylococcus aureus ATCC29213 was established; secondly, a mouse cornea infection model was directly induced by Pseudomonas aeruginosa ATCC9027. Infection model (mice were not immunosuppressed).
  • compound FT09 showed excellent in vivo antibacterial activity against Staphylococcus aureus ATCC29213 (positive bacteria) and Pseudomonas aeruginosa ATCC9027 (negative bacteria), which can reduce the amount of bacteria in the infected cornea. More than 99.9%, its efficacy is comparable to commercially available vancomycin or gatifloxacin. These results indicate that compound FT09 can cure mouse corneal infections caused by Staphylococcus aureus and Pseudomonas aeruginosa.

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Abstract

La présente invention concerne un dérivé de clofoctol, qui a la structure représentée par la formule générale (1). Le dérivé de clofoctol présente une efficacité élevée, une faible toxicité, un large spectre antibactérien, une vitesse de stérilisation rapide, une excellente activité antibactérienne in vivo, et une bonne pharmacopotentialité, et est capable d'éviter de manière efficace la génération d'une résistance aux médicaments antibactériens.
PCT/CN2022/088513 2022-04-22 2022-04-22 Dérivé de clofoctol, médicament antibactérien, procédé de préparation correspondant et utilisation associée Ceased WO2023201712A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024223624A1 (fr) 2023-04-25 2024-10-31 Institut National de la Santé et de la Recherche Médicale Nouvelle formulation de clofoctol

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