Application of triterpenoid compounds or pharmaceutically acceptable salts thereof in the preparation of antibacterial compositions

Abstract

The present application relates to the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial pharmaceutical composition, in the preparation of a drug for preventing and treating bacterial infection, in the preparation of an antibacterial product, as an antibacterial agent, and as an inhibitor of FtsZ protein. The triterpenoid compound has high bactericidal activity against some antibiotic-resistant strains, and in addition, has a broad-spectrum antibacterial activity, and has a strong killing effect on a variety of common pathogenic bacteria. In the triterpenoid compound of formula (I), it is ‑CH=CH‑ or ‑CH2‑CHR1‑, R1 is a pyranose ring glycosyl, a furanose ring glycosyl, or a substituted form of any of the foregoing glycosyls, R8 is a substituent having 5 to 20 carbon atoms, R2 and R3 are monovalent groups, or are connected to each other and adjacent carbon atoms to form a six-membered carbon ring, and the six-membered carbon ring may be substituted or unsubstituted.

Description

Technical Field

[0001] The present application relates to the field of antibacterial technology, and in particular to the use of triterpenoid compounds or pharmaceutically acceptable salts thereof in the preparation of antibacterial compositions, and further to the use of triterpenoid compounds or pharmaceutically acceptable salts thereof in the preparation of antibacterial pharmaceutical compositions, in the preparation of drugs for preventing and treating bacterial infections, in the preparation of antibacterial products, as antibacterial agents, and as FtsZ protein inhibitors. Background Art

[0002] With the widespread use of antibiotics, especially the abuse of antibiotics, the resistance of bacteria to commonly used antibiotics has been increasing, and the continuous emergence of resistant bacteria has reduced the efficacy of antibiotics. This has led to new challenges in the treatment of bacterial infections, and some resistant bacterial infections cannot even find effective treatments. For example, for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), the current antibiotic treatment effects are not ideal. The development of drugs with antibacterial activity against resistant strains is a major problem that needs to be solved urgently. Summary of the invention

[0003] Based on this, the purpose of the present invention includes providing the use of triterpenoid compounds or pharmaceutically acceptable salts thereof in the preparation of antibacterial compositions, and further relates to the use of triterpenoid compounds or pharmaceutically acceptable salts thereof in the preparation of antibacterial pharmaceutical compositions, in the preparation of drugs for preventing and treating bacterial infections, in the preparation of antibacterial products, as antibacterial agents, and as FtsZ protein inhibitors. The triterpenoid compounds have high bactericidal activity against some antibiotic-resistant strains, and in addition, have broad-spectrum antibacterial activity, and have strong killing effects on a variety of common pathogenic bacteria.

[0004] In the first aspect of the present application, there is provided a use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial composition.

[0005]

[0006] in, is -CH=CH- or -CH2-CHR1-;

[0007] R1 is selected from any one of a pyranose ring group, a furanose ring group, and a group in which one -OH of any of the aforementioned groups is acetylated; and any of the aforementioned groups in which one -OH is acetylated;

[0008] R2 is -(CH2)2-C(=O)-O-R4, R3 is -CH(=CH2)-CH3, or R2 and R3 are both -(CR5R6)2- and R2, R3 and adjacent carbon atoms form a 6-membered saturated ring, and any R5 and any R6 are independently H, methyl or -OR7;

[0009] R4 and any one of R7 are independently selected from H, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 3-6 heterocycloalkyl and substituted or unsubstituted phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of heteroatoms X1 in the heterocycloalkyl group is one or more; 1-6 Alkyl, substituted C 3-6 Cycloalkyl, substituted C 3-6 In heterocycloalkyl and substituted phenyl groups, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 The heterocycloalkyl and phenyl groups are independently substituted by one or more Q1, any Q1 being independently selected from -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl (CH3C(=O)-O-CH2-), C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[O-divalent C 5-6 Heterocycloalkyl] n -OH, wherein the substituted -O-divalent C 5-6 The heterocycloalkyl-OH is substituted by one or more Q2, any Q2 is independently -CH3 or -OH, -CH3 and -OH are in the -O-divalent C 5-6 The number of all Q2 in heterocycloalkyl-OH is independently 1 to 4, and the divalent C 5-6 The ring atoms in the heterocycloalkyl group include heteroatoms X2, wherein the heteroatoms X2 are selected from O and N, divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group is one or more, and n is 0, 1, 2, 3, 4 or 5;

[0010] R8 is selected from: Where R a and R bare independently selected from H, -OH, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 1-6 Alkyl-O-, substituted or unsubstituted C 3-6 Cycloalkyl-O- and substituted or unsubstituted C 3-6 Heterocycloalkyl-O-, wherein the substituted C 1-6 Alkyl, substituted C 1-6 Alkyl-O-, substituted C 3-6 Cycloalkyl-O- and substituted C 3-6 Heterocycloalkyl-O-, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O- and C 3-6 The heterocycloalkyl-O- is independently substituted by one or more Q3, any Q3 being independently selected from: -OH, methyl, ethyl, acetyl, methoxy, ethoxy, -F, -Cl and -Br; C 3-6 The ring atoms in the heterocycloalkyl group include a heteroatom X3, and the heteroatom X3 is selected from O and N.

[0011] In the second aspect of the present application, there is provided the use of a triterpene compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial pharmaceutical composition, wherein the triterpene compound of formula (I) is as defined in the first aspect of the present application; the antibacterial pharmaceutical composition comprises a triterpene compound of formula (I) and a pharmaceutically acceptable carrier.

[0012] In the third aspect of the present application, there is provided the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for preventing and treating bacterial infection, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application.

[0013] Based on any suitable manner of the present application, in some further embodiments, the bacterial infection includes a drug-resistant bacterial infection disease, and the drug-resistant bacterial infection disease includes a disease caused by infection with at least one of methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and linezolid-resistant Enterococcus.

[0014] In the fourth aspect of the present application, there is provided the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial product, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application.

[0015] In some embodiments, the antibacterial product includes at least one of medicines, medical devices, daily necessities, cosmetics and packaging supplies, and the daily necessities include one or more of cleaning supplies, sanitary care supplies, bedding, kitchen utensils, dining utensils and toys.

[0016] In the fifth aspect of the present application, there is provided the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof as an antibacterial agent, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application; the use is for non-diagnostic and therapeutic purposes.

[0017] In the sixth aspect of the present application, there is provided the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof as an FtsZ protein inhibitor, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application; the use is for non-diagnostic and therapeutic purposes.

[0018] Based on any suitable method of the present application, in some further embodiments, the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof has a killing effect on any one, any two or all of methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and linezolid-resistant Enterococcus. In some further embodiments, the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof also has a killing effect on one, more or all of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus.

[0019] Based on any suitable method of the present application, in some further embodiments, the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof is used in any suitable form of any of the following groups:

[0020] Preparations shown in Group A: tablets, capsules, granules, pills, ointments, solutions, suspensions, emulsions and creams;

[0021] Preparations shown in Group B: oral solution, lozenge, injection, suppository, spray, drop, patch and tube feeding preparations;

[0022] The form shown in group C: surface coating of a solid product and dopant in a solid product, wherein the solid product at least includes a plastic product.

[0023] After a lot of experimental exploration, the inventors of the present application unexpectedly discovered that a class of triterpenoid compounds has high bactericidal activity against some antibiotic-resistant strains, and in addition, it also has broad-spectrum antibacterial activity and has a strong killing effect on a variety of common pathogenic bacteria. Specifically, the triterpenoid compound of formula (I) has a high bactericidal activity against at least one of methicillin-gold-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci, and in addition, it also has a strong killing effect on one, multiple or all of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic streptococci, beta-hemolytic streptococci, Enterococcus faecalis, vancomycin-resistant enterococci, linezolid-resistant enterococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present application and to more completely understand the present application and its beneficial effects, the following is a brief introduction to the drawings required for the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application, and those skilled in the art can obtain other drawings based on these drawings without creative work.

[0025] Figure 1 Schematic diagram of the binding mode of triterpenoid compounds and FtsZ in one embodiment of the present application: wherein (A) is a visualization schematic diagram of the docking of compound 8 and FtsZ, and (B) is a surface diagram of the interaction between compound 8 and FtsZ.

[0026] Figure 2 Schematic diagram of the binding mode of triterpenoid compounds and FtsZ in one embodiment of the present application: wherein (A) is a visualization schematic diagram of the docking of compound 11 and FtsZ, and (B) is a surface diagram of the interaction between compound 11 and FtsZ.

[0027] Figure 3 Schematic diagram of the binding pocket of FtsZ, where the light-colored part is the binding pocket area. DETAILED DESCRIPTION

[0028] The present application will be further described in detail below in conjunction with the accompanying drawings, embodiments and examples. It should be understood that these embodiments and examples are only used to illustrate the present application and are not used to limit the scope of the present application. The purpose of providing these embodiments and examples is to make the understanding of the disclosure of the present application more thorough and comprehensive. It should also be understood that the present application can be implemented in many different forms and is not limited to the embodiments and examples described herein. Those skilled in the art can make various changes or modifications without violating the connotation of the present application, and the equivalent form obtained also falls within the protection scope of the present application. For example, the features described or described as part of an embodiment can be combined in another embodiment in a suitable manner to produce a new embodiment. In addition, in the description below, a large number of specific details are given in order to provide a more comprehensive understanding of the present application. It should be understood that the present application can be implemented without one or more of these details.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing implementation modes and embodiments and are not intended to limit this application.

[0030] the term

[0031] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0032] The terms "and / or", "or / and", and "and / or" used herein include any one of two or more related listed items, and also include any and all combinations of the related listed items, which include any combination of any two related listed items, any more related listed items, or all related listed items. For example, "A and / or B" includes three parallel solutions: A, B, and "a combination of A and B".

[0033] In the present application, "plurality", "multiple", "multiple times", "multiple", "several", etc., unless otherwise specified, refer to a quantity greater than 2 or equal to 2. For example, "one or more" means one or greater than or equal to two.

[0034] In this application, unless otherwise specified, "one or more" means any one of the listed items or any combination of the listed items. Similarly, "one or more" and the like, when used in other ways to mean "one or more", are also understood in the same way unless otherwise specified.

[0035] As used herein, "combination thereof", "any combination thereof", "any combination thereof" etc. include all suitable combinations of any two or more of the listed items.

[0036] Herein, the “suitable” mentioned in “suitable combination”, “suitable method”, “any suitable method”, etc., shall be based on the ability to implement the technical solution of this application, solve the technical problems of this application, and achieve the expected technical effects of this application.

[0037] Herein, "preferred", "better", "more preferred", and "suitable" are only used to describe implementation methods or examples with better effects, and it should be understood that they do not constitute a limitation on the scope of protection of this application. If multiple "preferred" items appear in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction, each "preferred" item is independent.

[0038] In this application, "further", "further", "particularly", "for example", "such as", "example", "for example", etc. are used for descriptive purposes, indicating that the previous and subsequent different technical solutions are related in terms of the content covered, but should not be understood as a limitation on the previous technical solution, nor can it be understood as a limitation on the protection scope of this application. In this application, unless otherwise specified, A (such as B) means that B is a non-limiting example of A, and it can be understood that A is not limited to B.

[0039] In this application, "optionally", "optional", and "optional" mean optional or dispensable, that is, any one of the two parallel schemes of "yes" or "no". If multiple "options" appear in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction, each "optional" is independent.

[0040] In the present application, the terms "first", "second", "third", "fourth", etc. in "the first aspect", "the second aspect", "the third aspect", "the fourth aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", "fourth", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0041] The terms "containing", "including" and "comprising" used in this application are synonymous, which are inclusive or open-ended and do not exclude additional, uncited members. Unless otherwise specified, open technical features or technical solutions described by words such as "containing", "including" and "comprising" can be regarded as providing both closed features or solutions consisting of the listed members and open features or solutions that include additional members in addition to the listed members. For example, A includes a1, a2 and a3. Unless otherwise specified, it may also include other members or may not include additional members. It can be regarded as providing both the feature or solution of "A consists of a1, a2 and a3" or "A is selected from a1, a2 and a3", and the feature or solution of "A not only includes a1, a2 and a3, but also includes other members". The "members" involved here can be materials or components, structures, elements, instruments, etc., and can also be actions, conditions for the occurrence of actions, timing, states, etc.

[0042] In this application, the technical features or technical solutions described in an open language include closed technical features or technical solutions composed of the listed contents, and also include open technical features or technical solutions containing the listed contents.

[0043] In the present application, when it comes to a numerical interval (i.e., a numerical range), unless otherwise specified, the distribution of the optional numerical values ​​in the numerical interval is considered to be continuous, and includes the two numerical endpoints (i.e., the minimum and maximum values) of the numerical interval, and each numerical value between the two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to an integer in the numerical interval, it includes the two endpoint integers of the numerical range, and each integer between the two endpoints, which is equivalent to directly listing each integer. When multiple numerical ranges are provided to describe features or characteristics, these numerical ranges can be merged. In other words, unless otherwise specified, the numerical range disclosed herein should be understood to include any and all sub-ranges included therein. The "numerical value" in the numerical interval can be any quantitative value, such as a number, a percentage, a ratio, etc. "Numerical interval" allows broadly including numerical interval types such as percentage intervals, ratio intervals, and ratio intervals.

[0044] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference separately. Unless they conflict with the invention purpose and / or technical solution of this application, the cited documents involved in this application are cited with all contents and all purposes. When the cited documents are involved in this application, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also cited. When the cited documents are involved in this application, the examples and preferred methods of the cited relevant technical features can also be incorporated into this application as references, but are limited to the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, the present application shall prevail or be modified adaptively according to the description of this application.

[0045] In this application, if there are multiple steps involved in the method flow, unless there is a clear different description in this document, there is no strict order restriction for the execution of these steps, and they can be executed in other orders than described. Moreover, any step can include multiple sub-steps or multiple stages, and these sub-steps or stages are not necessarily executed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be executed in turn, alternating or simultaneously with other steps or parts of sub-steps or stages of other steps.

[0046] The mass or weight of the relevant components mentioned in the specification of the embodiments of the present application may not only refer to the specific content of each component, but also indicate the proportional relationship of the mass or weight between the components. Therefore, as long as the content of the relevant components is proportionally enlarged or reduced according to the specification of the embodiments of the present application, it is within the scope disclosed in the specification of the embodiments of the present application. Specifically, the mass or weight described in the specification of the embodiments of the present application may be units known in the chemical industry such as μg, mg, g, and kg.

[0047] The temperature parameters in this application, unless otherwise specified, are allowed to be either constant temperature treatment or to vary within a certain temperature range. It should be understood that the constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are allowed.

[0048] In the present application, the term "room temperature" or "normal temperature" generally refers to 4°C to 35°C, for example, 20°C ± 5°C. In some embodiments of the present application, "room temperature" or "normal temperature" refers to 10°C to 30°C. In some embodiments of the present application, "room temperature" or "normal temperature" refers to 20°C to 30°C.

[0049] In this application, when referring to the unit of a data range, if there is a unit only after the right endpoint, it means that the units of the left endpoint and the right endpoint are the same. For example, 3-5h means that the units of the left endpoint "3" and the right endpoint "5" are both h (hours).

[0050] As used herein, the term "hydrocarbon" or "hydrocarbon compound" refers to a compound composed of carbon atoms and hydrogen atoms.

[0051] Herein, the term "aromatic hydrocarbon" refers to a hydrocarbon compound having aromaticity, which includes a ring structure having aromaticity in its structure and thus has an aromatic ring.

[0052] Herein, the term "aliphatic hydrocarbon" refers to a hydrocarbon compound that does not have aromaticity, and may also be referred to as "non-aromatic hydrocarbon".

[0053] As used herein, the term "alkyl" refers to a monovalent residue formed by the loss of a hydrogen atom from a saturated hydrocarbon containing a primary (normal) carbon atom, a secondary carbon atom, a tertiary carbon atom, a quaternary carbon atom, or a combination thereof. Phrases containing this term, such as "C 1-6"Alkyl" refers to an alkyl group containing 1 to 6 carbon atoms, and each occurrence may be independently C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl or C6 alkyl. Suitable examples include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3), 2-methyl -1-propyl (i-Bu, i-butyl, -CH2CH(CH3)2), 2-butyl (s-Bu, s-butyl, -CH(CH3)CH2CH3), 2-methyl-2-propyl (t-Bu, t-butyl, -C(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3 -methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH 2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2) and 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3.

[0054] As used herein, the term "cycloalkyl" refers to a monovalent residue formed by a non-aromatic hydrocarbon (which may be a saturated hydrocarbon or an unsaturated hydrocarbon) containing a ring structure losing a hydrogen atom on the ring, i.e., directly forming a monovalent attachment site on the ring. Phrases containing this term, such as "C 3-6 "Cycloalkyl" refers to a cycloalkyl containing 3 to 6 carbon atoms, each occurrence of which may be independently C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl or C6 cycloalkyl. Suitable examples include, but are not limited to, cyclopropyl Cyclobutyl Cyclopentyl Cyclohexyl Cyclohexenyl (including but not limited to ).

[0055] As used herein, the term "cycloalkyl" refers to a saturated cyclic hydrocarbon group, which refers to a monovalent residue formed by a saturated hydrocarbon containing a ring structure losing a hydrogen atom on the ring, that is, directly forming a monovalent attachment site on the ring. Phrases containing this term, such as "C 3-6 "Cycloalkyl" refers to a cycloalkyl group containing 3 to 6 carbon atoms, each occurrence of which can be independently C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl or C6 cycloalkyl. Suitable examples include, but are not limited to: cyclopropyl Cyclobutyl Cyclopentyl Cyclohexyl

[0056] As used herein, the term "heterocycloalkyl" refers to a monovalent group in which at least one ring-membering atom in a cycloalkyl group is replaced by a heteroatom, and at least one carbon atom remains in the ring-membering atom. Phrases containing this term, such as "C 3-6 "Heterocycloalkyl" refers to a heterocycloalkyl group containing 3 to 6 carbon atoms, each occurrence of which can be independently C3 heterocycloalkyl, C4 heterocycloalkyl, C5 heterocycloalkyl or C6 heterocycloalkyl. Suitable examples of the ring structure in the heterocycloalkyl group are tetrahydrofuran ring Tetrahydrofuran ring

[0057] In the present application, the term "heteroatom" refers to an atom that is not hydrogen and not carbon, such as an oxygen atom (O), a nitrogen atom (N), a sulfur atom (S), a phosphorus atom (P), chlorine (Cl), bromine (Br), iodine (I), etc.

[0058] As used herein, the term "alkoxy" refers to a group of the structure "alkyl-O-", i.e., an alkyl group as defined above is attached to the adjacent group via an oxygen atom. Phrases containing this term, such as "C 1-6 "Alkoxy" means that the alkyl portion contains 1-6 carbon atoms and each occurrence can be independently C1alkoxy, C4alkoxy, C5alkoxy or C6alkoxy. Suitable examples include, but are not limited to, methoxy (-O-CH3 or -OMe), ethoxy (-O-CH2CH3 or -OEt) and tert-butoxy (-OC(CH3)3 or -OtBu).

[0059] As used herein, the term "divalent heterocycloalkyl" refers to a divalent residue having two monovalent radical centers derived from a heterocycloalkyl group by losing a hydrogen atom on the ring. Phrases containing this term, such as "divalent C 5-6"Heterocycloalkyl" refers to a divalent heterocycloalkyl group containing 5 to 6 carbon atoms, which can be independently a divalent C5 heterocycloalkyl group or a divalent C6 heterocycloalkyl group each time it appears. Suitable examples include, but are not limited to, divalent heterocycloalkyl groups derived from the following heterocycloalkyl groups: tetrahydrofuranyl, tetrahydropyranyl. Specific examples of divalent heterocycloalkyl groups include wait.

[0060] In the present application, unless otherwise specified, "carbocycle" refers to a ring in which all the ring atoms are carbon atoms.

[0061] After a lot of experimental exploration, the inventors of the present application unexpectedly discovered that a class of triterpenoid compounds has high bactericidal activity against some antibiotic-resistant strains. In addition, it also has broad-spectrum antibacterial activity and has a strong killing effect on a variety of common pathogenic bacteria. Specifically, the triterpenoid compounds of formula (I) have high bactericidal activity against at least one of methicillin-gold-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci. In addition, the triterpenoid compounds of formula (I) also have a strong killing effect on one, multiple or all of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic streptococci, beta-hemolytic streptococci, Enterococcus faecalis, vancomycin-resistant enterococci, linezolid-resistant enterococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus.

[0062] In the first aspect of the present application, a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof is provided for use in preparing an antibacterial composition. In some embodiments, the triterpenoid compound of formula (I) has a structure as shown in formula (I):

[0063]

[0064] In formula (I), Carbon-carbon double bond or carbon-carbon single bond and A1 and A2 each include a ring-forming carbon atom; The two ring-forming carbon atoms in A1-A2 are not substituted, the ring-forming carbon atom in A1 is not substituted and the ring-forming carbon atom in A2 is substituted by a substituent; R8 is a substituent having 5 to 20 carbon atoms; R2 and R3 are monovalent groups, or are connected to each other and adjacent carbon atoms to form a six-membered carbon ring, which can be substituted or unsubstituted. Among them, the substituent connected to the ring-forming carbon atom in A2 can be recorded as R1, R1 is a monovalent group, and R1 can be a pyranose ring glycosyl, a furanose ring glycosyl, or a substituted form of any of the foregoing glycosyls.

[0065] when When it is a carbon-carbon double bond, A1 is -CH=; when When it is a carbon-carbon single bond, A1 is a methylene group (-CH2-).

[0066] when When it is a carbon-carbon double bond, A2 is =CH-; when When it is a carbon-carbon single bond, A2 is a methylene group substituted by R1 (-CHR1-.

[0067] In the present application, "pharmaceutically acceptable salt" refers to a salt formed by a given compound and an acid or base that is suitable for use as a drug. Pharmaceutically acceptable salts include inorganic salts and organic salts.

[0068] In some embodiments, in the triterpenoid compound of formula (I), It is -CH=CH- or -CH2-CHR1-, R1 is a pyranose ring glycosyl, a furanose ring glycosyl, or a substituted form of any of the foregoing glycosyls, R8 is a substituent having 5 to 20 carbon atoms, R2 and R3 are respectively monovalent groups, or are connected to each other and adjacent carbon atoms to form a six-membered carbocyclic ring, which may be substituted or unsubstituted.

[0069] In the triterpenoid compound of formula (I), It can be a carbon-carbon double bond or a carbon-carbon single bond.

[0070] In some embodiments, the ring-forming carbon atoms in A1 and A2 may be independently unsubstituted, that is, only connected to hydrogen atoms.

[0071] In other embodiments, the ring-forming carbon atom in A1 is unsubstituted, and the ring-forming carbon atom in A2 is connected to a substituent, and the substituent connected to the ring-forming carbon atom in A2 can be recorded as R1. R1 can be a pyranose ring glycosyl, a furanose ring glycosyl, or a substituted form of any of the foregoing glycosyls, wherein any hydroxyl group (-OH) in the pyranose ring glycosyl and the furanose ring glycosyl can be substituted by a substituent selected from the following group: acetyl. For example, when substituted by acetyl, an ester bond -C(=O)-O- is formed with the hydroxyl group.

[0072] In some embodiments, the attachment sites in the pyranose ring and furanose ring are located at the hydroxyl groups of their respective acetal structures, such as the * position in -CO-CH(O-*)-C, and the carbon atoms at both ends are ring-forming carbon atoms, such as non-limiting examples. wait.

[0073] In some embodiments, It is -CH=CH- or -CH2-CHR1-.

[0074] In some embodiments, It is -CH=CH-.

[0075] In some embodiments, It is -CH2-CHR1-.

[0076] In some embodiments, R1 is selected from any one of a pyranose ring group, a furanose ring group, and any one of the aforementioned groups in which one -OH is acetylated.

[0077] In some embodiments, R1 is a pyranosyl or furanosyl ring.

[0078] In some embodiments, R1 is any one of arabinofuranosyl, arabinopyranosyl, rhamnopyranosyl, and any one of the foregoing groups in which one -OH is acetylated.

[0079] In some embodiments, R1 is arabinofuranosyl, arabinopyranosyl, or rhamnopyranosyl.

[0080] Non-limiting examples of furanoarabinosyl groups are

[0081] Non-limiting examples of arabinopyranosyl groups are

[0082] Non-limiting examples of rhamnopyranosyl groups are

[0083] In some embodiments, R1 is selected from and any of the aforementioned groups in which one -OH group is acetylated.

[0084] In some embodiments, R1 is

[0085] In some embodiments, R1 is selected from Any of

[0086] In some embodiments, R1 is arabinopyranosyl or rhamnopyranosyl.

[0087] In some embodiments, R1 is any one of α-L-arabinopyranosyl, α-L-rhamnopyranosyl, β-D-rhamnopyranosyl, and any one of the foregoing groups in which one -OH is acetylated.

[0088] In some embodiments, R1 is α-L-arabinopyranosyl, α-L-rhamnopyranosyl, or β-D-rhamnopyranosyl.

[0089] In some embodiments, R1 is and any of the aforementioned groups in which one -OH group is acetylated.

[0090] In some embodiments, R1 is

[0091] In some embodiments, R1 is

[0092] In some embodiments, R1 is

[0093] In the triterpene compound of formula (I), R8 is a substituent having 5 to 20 carbon atoms (further can be 5 to 13 carbon atoms, further can be 5, 6, 7, 8, 9, 10, 11, 12 or 13 carbon atoms), further is a substituent having 5 to 20 non-hydrogen atoms (further can be 5 to 15 non-hydrogen atoms, further can be 6 to 15 non-hydrogen atoms, further can be 6 to 14 non-hydrogen atoms, further can be, for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 non-hydrogen atoms).

[0094] As used herein, the term "non-hydrogen atom" refers to an atom that is not hydrogen.

[0095] The non-hydrogen atom in R8 may be, but is not limited to, a carbon atom or an oxygen atom.

[0096] R8 may contain a monocyclic structure or an open-chain structure. The monocyclic structure in R8 may be a full carbon ring or may have an oxygen heteroatom, and the oxygen heteroatom may be in the form of an ether bond (-O-, with both ends connected to carbon atoms).

[0097] R8 may contain a carbon-carbon double bond (C=C) or a carbon-oxygen double bond (C=O), and may be a saturated structure.

[0098] In some embodiments, R8 contains a hydroxyl group (—OH) or an ester group (—C(═O)—O—).

[0099] In some embodiments, R8 is selected from: Among them, R a and R b can be independently selected from H, hydroxyl (-OH), substituted or unsubstituted alkyl (alkyl can be C 1-6 Alkyl), substituted or unsubstituted alkoxy (alkoxy can be C 1-6 Alkyl-O-), substituted or unsubstituted cycloalkyloxy (cycloalkyloxy may be C 3-6 Cycloalkyl-O-), substituted or unsubstituted heterocycloalkyloxy (heterocycloalkyloxy may be C 3-6In the definition of R8, among the substituted alkyl, substituted alkoxy, substituted cycloalkyloxy and substituted heterocycloalkyloxy, the alkyl (such as C 1-6 Alkyl), alkoxy (such as C 1-6 Alkyl-O-), cycloalkyloxy (such as C 3-6 Cycloalkyl-O-) and heterocycloalkyloxy (such as C 3-6 heterocycloalkyl-O-) are independently substituted by one or more substituents Q3, any of which is independently selected from -OH, C 1-3 Alkyl (such as methyl, ethyl), C 1-3 Alkoxy (i.e. C 1-3 Alkyl-O, such as methoxy, ethoxy) and halogen (such as fluoro (-F), chloro (-Cl), bromo (-Br)). In the definition of R8, "heterocycloalkyl (such as C 3-6 The ring atoms in the "heterocycloalkyl" include heteroatoms X3, which may be selected from O and N, and may further be O. This definition applies to independently described heterocycloalkyls (such as C 3-6 heterocycloalkyl), also applies to heterocycloalkyloxy (such as heterocycloalkyl-O-, further such as C 3-6 In the definition of R8, heterocycloalkyl (such as C 3-6 The number of the heteroatom X3 in the heterocycloalkyl group (such as C 3-6 The number of the heteroatom X3 in the heterocycloalkyl group is 1.

[0100] In this application, unless otherwise specified, the term “C 1-6 "Alkyl" may independently be preferably C 1-5 Alkyl, further optionally C 1-4 Alkyl, further optionally C 1-3 Alkyl. Any occurrence of “C 1-6 "Alkyl" may be independently selected from C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl and C6 alkyl. 1-6 "Alkyl" may be independently selected from: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl. In some embodiments, C 1-6 The alkyl group may preferably be methyl or ethyl. 1-6 The alkyl group may preferably be a methyl group.

[0101] In this application, unless otherwise specified, the term “C 3-6 The "cycloalkyl" may be independently preferably C 3-5 Cycloalkyl, further optionally C 3-4Cycloalkyl, further optionally C3 cycloalkyl. 3-6 The "cycloalkyl" may be independently selected from C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl and C6 cycloalkyl. 3-6 The "cycloalkyl" may be independently selected from: cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0102] In this application, unless otherwise specified, the term “C 3-6 The heterocycloalkyl group may be independently preferably C 3-5 Heterocycloalkyl, further optionally C 3-4 Heterocycloalkyl, further optionally C3 heterocycloalkyl. 3-6 "Heterocycloalkyl" may be independently selected from C3 heterocycloalkyl, C4 heterocycloalkyl, C5 heterocycloalkyl and C6 heterocycloalkyl. 3-6 The ring structure of "heterocycloalkyl" can be independently selected from: ethylene oxide ring Tetrahydrofuran ring and tetrahydropyran ring The corresponding heterocycloalkyl groups are oxirane, tetrahydrofuranyl and tetrahydropyranyl respectively.

[0103] In some embodiments, in R8, R a and R b are independently H, -OH, C 1-3 Alkyl-O-, pyranose ring type glycosyl or furanose ring type glycosyl.

[0104] In some embodiments, in R8, R a and R b are each independently H, -OH, methoxy or α-L-arabinopyranosyl.

[0105] In some embodiments, in R8, R a and R b are each independently H, -OH or methoxy.

[0106] In some embodiments, R a is -OH or a pyranose ring, further can be -OH or a pyranose arabinose, further can be -OH or In some embodiments, R a In some embodiments, R a is a pyranose ring type sugar group, further can be a pyranose arabinose group, further can be

[0107] In some embodiments, R bis -OH or methoxy (CH3O-). In some embodiments, R b In some embodiments, R b It is a methoxy group.

[0108] In some embodiments, R8 is

[0109] In some embodiments, R8 is R a for

[0110] In some embodiments, R8 is

[0111] In the triterpenoid compound of formula (I), R2 and R3 may be monovalent groups respectively, or they may be connected to each other and to adjacent carbon atoms to form a six-membered carbon ring, and the six-membered carbon ring may be substituted or unsubstituted.

[0112] In some embodiments, R2 is -(CH2)2-C(=O)-O-R4, and R3 is -CH(=CH2)-CH3.

[0113] R4 can be selected from H, substituted or unsubstituted alkyl (alkyl can be C 1-6 Alkyl), substituted or unsubstituted cycloalkyl (cycloalkyl can be C 3-6 cycloalkyl), substituted or unsubstituted heterocycloalkyl (heterocycloalkyl may be C 3-6 Heterocycloalkyl) and substituted or unsubstituted phenyl; wherein the heterocycloalkyl (such as C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, which may be selected from O and N, and may further be O. In the definition of R4, the heterocycloalkyl group (such as C 3-6 The number of the heteroatom X1 in the heterocycloalkyl group (such as C 3-6 The number of the heteroatom X1 in the heterocycloalkyl group is 1.

[0114] In the definition of R4, among the substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl and substituted phenyl, the alkyl, cycloalkyl, heterocycloalkyl and phenyl can be independently substituted by one or more Q1, any Q1 is independently selected from -F, -Cl, -Br, -NH2, -NO2, acetyl (CH3C(=O)-), acetoxymethyl (CH3C(=O)-O-CH2-), C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[O-divalent C5-6 Heterocycloalkyl] n -OH, n is an integer (can be 0 to 5, further can be 0 to 4, further can be 0 to 3, for example, 0, 1, 2, 3, 4 or 5).

[0115] In some embodiments, in the definition of R4, among the substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl and substituted phenyl, the alkyl, cycloalkyl, heterocycloalkyl and phenyl can be independently substituted by one or more Q1, any Q1 is independently selected from -OH, -F, -Cl, -Br, -NH2, -NO2, acetyl (CH3C(=O)-), acetoxymethyl (CH3C(=O)-O-CH2-), C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[O-divalent C 5-6 Heterocycloalkyl] n -OH, n is an integer (n may be 1 to 5, further may be 1 to 4, further may be 1 to 3, for example, 1, 2, 3, 4 or 5).

[0116] In some embodiments, in the definition of R4, "substituted -[O-divalent C 5-6 Heterocycloalkyl] n -[O-divalent C 5-6 Heterocycloalkyl] n -OH is substituted by one or more Q2, any of which can be independently an alkyl group (optionally C 1-3 Alkyl, further optionally -CH3) or -OH, alkyl (optionally C 1-3 The number of alkyl groups (optionally -CH3) and -OH in all Q2 can be independently 1 to 4, and further can be 1 to 3, such as 1, 2, 3 or 4.

[0117] In the definition of R4, the divalent C 5-6 The ring atoms in the heterocycloalkyl group include a heteroatom X2, and the heteroatom X2 may be selected from O and N, and may further be O.

[0118] In the definition of Q1, the divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group may be one or more, for example, 1 or 2; in some embodiments, the divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group is 1.

[0119] In some embodiments, in the definition of R4, any Q1 is independently selected from -OH, -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl, C 1-6Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[OZ] n -OH, wherein -OZ- is a divalent pyranose ring group or a divalent furanose ring group, Z contains -OH, and n is 1, 2, 3, 4 or 5. When n is greater than 1, adjacent -OZ- are connected by glycosidic bonds.

[0120] In some embodiments, R4 is H, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl or phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of the heteroatom X1 in the heterocycloalkyl group is one or two.

[0121] In some embodiments, R4 is H, methyl, ethyl or phenyl.

[0122] In some embodiments, "substituted or unsubstituted -[O-divalent C 5-6 Heterocycloalkyl] n -OH" can also be -[OC 5-6 Heterocycloalkyl(OH) 0-4 (CH3) 0-4 ] n -OH, n is defined as above. 5-6 Heterocycloalkyl] n -OH any "C 5-6 The "heterocycloalkyl" is a divalent group, which may be independently substituted by 0 to 4 -OH hydroxyl groups, and may also be independently substituted by 0 to 4 methyl groups.

[0123] In some embodiments, R2 and R3 are connected to each other and adjacent carbon atoms to form a six-membered carbocyclic ring, which may be substituted or unsubstituted. Further, the six-membered carbocyclic ring may be substituted by one or more groups selected from the group consisting of: 1-3 Alkyl (such as methyl, ethyl) and R7-O-.

[0124] R7 may be the same as or different from R4.

[0125] In some embodiments, R7 can be selected from H, substituted or unsubstituted alkyl (alkyl can be C 1-6 Alkyl), substituted or unsubstituted cycloalkyl (cycloalkyl can be C 3-6 Cycloalkyl) and substituted or unsubstituted heterocycloalkyl (heterocycloalkyl may be C 3-6 Heterocycloalkyl); wherein, heterocycloalkyl (such as C3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, which may be selected from O and N, and may further be O. In the definition of R7, the heterocycloalkyl group (such as C 3-6 The number of the heteroatom X1 in the heterocycloalkyl group (such as C 3-6 The number of the heteroatom X1 in the heterocycloalkyl group is 1.

[0126] In the definition of R7, among the substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl and substituted phenyl, the alkyl, cycloalkyl, heterocycloalkyl and phenyl can be independently substituted by one or more Q1, any Q1 is independently selected from -F, -Cl, -Br, -NH2, -NO2, acetyl (CH3C(=O)-), acetoxymethyl (CH3C(=O)-O-CH2-), C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[O-divalent C 5-6 Heterocycloalkyl] n -OH, n is an integer (can be 0 to 5, further can be 0 to 4, further can be 0 to 3, for example, 0, 1, 2, 3, 4 or 5).

[0127] In some embodiments, in the definition of R7, among the substituted alkyl, substituted cycloalkyl and substituted heterocycloalkyl, the alkyl, cycloalkyl and heterocycloalkyl are independently substituted by one or more Q1, any Q1 is independently selected from -OH, -F, -Cl, -Br, -NH2, -NO2, acetyl (CH3C(=O)-), acetoxymethyl (CH3C(=O)-O-CH2-), C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, substituted or unsubstituted-[O-divalent C 5-6 Heterocycloalkyl] n -OH, n is an integer (n may be 1 to 5, further may be 1 to 4, further may be 1 to 3, for example, 1, 2, 3, 4 or 5).

[0128] In some embodiments, in the definition of R7, "substituted-[O-divalent C 5-6 Heterocycloalkyl] n -[O-divalent C 5-6 Heterocycloalkyl] n -OH is substituted by one or more Q2, any Q2 is independently alkyl (optionally C 1-3 Alkyl, further optionally -CH3) or -OH, alkyl (optionally C1-3 The number of alkyl groups (optionally -CH3) and -OH in all Q2 can be independently 1 to 4, and further can be 1 to 3, such as 1, 2, 3 or 4.

[0129] In the definition of R7, the divalent C 5-6 The ring atoms in the heterocycloalkyl group include a heteroatom X2, and the heteroatom X2 may be selected from O and N, and may further be O.

[0130] In the definition of R7 and Q1, the divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group may be one or more, for example, 1 or 2; in some embodiments, the divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group is 1.

[0131] In some embodiments, in the definition of R7, any Q1 is independently selected from -OH, -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[OZ] n -OH, wherein -OZ- is a divalent pyranose ring group or a divalent furanose ring group, Z contains -OH, and n is 1, 2, 3, 4 or 5. When n is greater than 1, adjacent -OZ- are connected by glycosidic bonds.

[0132] In some embodiments, any R7 is independently selected from H, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 3-6 heterocycloalkyl and substituted or unsubstituted phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of heteroatoms X1 in the heterocycloalkyl group is one or more; wherein the substituted C 1-6 Alkyl, substituted C 3-6 Cycloalkyl, substituted C 3-6 In heterocycloalkyl and substituted phenyl groups, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 The heterocycloalkyl and phenyl groups are independently substituted by one or more Q1, any Q1 being independently selected from -OH, -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6Cycloalkyl-O-, and substituted or unsubstituted-[OZ] n -OH, wherein -OZ- is a divalent pyranose ring group or a divalent furanose ring group, Z contains -OH, and n is 1, 2, 3, 4 or 5. When n is greater than 1, adjacent -OZ- are connected by glycosidic bonds.

[0133] In some embodiments, R7 is H, arabinopyranosyl, arabinopyranosyl with one hydroxyl group acetylated, arabinofuranosyl, arabinofuranosyl with one hydroxyl group acetylated, rhamnosyl, or rhamnosyl with one hydroxyl group acetylated. It can further be arabinopyranosyl, arabinopyranosyl with one hydroxyl group acetylated, arabinofuranosyl, arabinofuranosyl with one hydroxyl group acetylated, rhamnosyl, or rhamnosyl with one hydroxyl group acetylated.

[0134] In some embodiments, R7 is H, arabinopyranosyl, arabinofuranosyl or rhamnopyranosyl, and may further be arabinopyranosyl, arabinofuranosyl or rhamnopyranosyl.

[0135] In some embodiments, R7 is H, arabinofuranosyl or rhamnopyranosyl. It may further be arabinofuranosyl or rhamnopyranosyl.

[0136] In some embodiments, R7 is In some embodiments, R7 is In some embodiments, R7 is

[0137] In some embodiments, in the triterpenoid compound of formula (I), is -CH=CH- or -CH2-CHR1-;

[0138] R1 is selected from any one of a pyranose ring group, a furanose ring group, and a group in which one -OH of any of the aforementioned groups is acetylated; And any one of the above groups in which one -OH is acetylated; further optionally

[0139] R2 is -(CH2)2-C(=O)-O-R4, R3 is -CH(=CH2)-CH3, or R2 and R3 are both -(CR5R6)2- and R2, R3 and adjacent carbon atoms form a 6-membered saturated ring, and any R5 and any R6 are independently H, methyl or -OR7;

[0140] R4 and any one of R7 are independently selected from H, substituted or unsubstituted C 1-6Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, and substituted or unsubstituted C 3-6 heterocycloalkyl and substituted or unsubstituted phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of heteroatoms X1 in the heterocycloalkyl group is one or more; 1-6 Alkyl, substituted C 3-6 Cycloalkyl, substituted C 3-6 In heterocycloalkyl and substituted phenyl groups, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 The heterocycloalkyl and phenyl groups are independently substituted by one or more Q1 groups, any of which is independently selected from -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl, C1-6 alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, substituted or unsubstituted-[O-divalent C 5-6 Heterocycloalkyl] n -OH, wherein the substituted -O-divalent C 5-6 The heterocycloalkyl-OH is substituted by one or more Q2, any Q2 is independently -CH3 or -OH, -CH3 and -OH are in the -O-divalent C 5-6 The number of all Q2 in heterocycloalkyl-OH is independently 1 to 4, and the divalent C 5-6 The ring atoms in the heterocycloalkyl group include heteroatoms X2, wherein the heteroatoms X2 are selected from O and N, divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group is one or more, and n is 0, 1, 2, 3, 4 or 5;

[0141] R8 is selected from: Where R a and R b are independently selected from H, -OH, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 1-6 Alkyl-O-, substituted or unsubstituted C 3-6 Cycloalkyl-O- and substituted or unsubstituted C 3-6 Heterocycloalkyl-O-, wherein the substituted C 1-6 Alkyl, substituted C 1-6 Alkyl-O-, substituted C 3-6 Cycloalkyl-O- and substituted C 3-6 Heterocycloalkyl-O-, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6Cycloalkyl-O- and C 3-6 The heterocycloalkyl-O- is independently substituted by one or more Q3, any Q3 being independently selected from: -OH, methyl, ethyl, acetyl, methoxy, ethoxy, -F, -Cl and -Br; C 3-6 The ring atoms in the heterocycloalkyl group include a heteroatom X3, and the heteroatom X3 is selected from O and N (the heteroatom X3 may further be O).

[0142] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (II) or a compound of formula (III):

[0143]

[0144] R1, R2, R3 and R8 are as defined above respectively.

[0145] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ia), a compound of formula (Ib), or a compound of formula (Ic);

[0146]

[0147] R1, R2, R3, R4, R7 and R8 are as defined above respectively.

[0148] Based on any suitable embodiment of the present application, in some further embodiments, any C 1-6 The alkyl groups are independently C 1-4 The alkyl group may further be selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, further may be selected from methyl or ethyl, further may be selected from methyl.

[0149] Based on any suitable embodiment of the present application, in some further embodiments, any C 3-6 Cycloalkyl is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0150] Based on any suitable embodiment of the present application, in some further embodiments, any C 3-6 The heterocycloalkyl group is independently oxirane, tetrahydropyranyl or tetrahydrofuranyl, and can further be tetrahydropyranyl or tetrahydrofuranyl.

[0151] Based on any suitable embodiment of the present application, in some further embodiments, any divalent C 5-6 The heterocycloalkyl group is independently a divalent tetrahydropyranyl group or a divalent tetrahydrofuranyl group.

[0152] Based on any suitable embodiment of the present application, in some further embodiments,

[0153] Any C 1-6 The alkyl group is independently methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, and may further be methyl or ethyl, and may further be methyl;

[0154] Any C 3-6 Cycloalkyl is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

[0155] Any C 3-6 Heterocycloalkyl is independently oxirane, tetrahydropyranyl or tetrahydrofuranyl, and further can be tetrahydropyranyl or tetrahydrofuranyl;

[0156] Any bivalent C 5-6 The heterocycloalkyl group is independently a divalent tetrahydropyranyl group or a divalent tetrahydrofuranyl group.

[0157] Based on any suitable embodiment of the present application, in some further embodiments, the substituted or unsubstituted C 3-6 Heterocycloalkyl is Or a group in which one -OH in any of the aforementioned groups is acetylated.

[0158] Based on any suitable embodiment of the present application, in some further embodiments, the substituted or unsubstituted C 3-6 Heterocycloalkyl is

[0159] Based on any suitable embodiment of the present application, in some further embodiments, the substituted or unsubstituted C 3-6 The heterocycloalkyl group is selected from:

[0161] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ia) or a compound of formula (Ic), and R1 is a pyranose ring glycosyl or a furanose ring glycosyl. It can further be arabinopyranose or rhamnopyranose. It can further be

[0162] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ib) or a compound of formula (Ic), R4 is H, C 1-3 Alternatively, R4 may be H.

[0163] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ic); in R8, R a and R b are each independently H, -OH or methoxy.

[0164] In some embodiments, in the compound (Ia), R1 may be as defined above, and R1 may be R7 may be as defined above, and R7 may be R8 is

[0165] In some embodiments, in the compound (Ib), R4 is H, methyl, ethyl or phenyl (optionally H), and R8 is R a It can be defined as above, R a Optional

[0166] In some embodiments, in the compound (Ic), R1 is R4 is H, methyl, ethyl or phenyl, R8 is

[0167] In some embodiments, the triterpenoid compound of formula (I) is compound (Ic), R1 is arabinopyranosyl or rhamnopyranosyl, and R1 can be R4 is H or phenyl, R8 is

[0168] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ic); the compound of formula (Ic) satisfies one, two or three of the following characteristics:

[0169] R1 is a pyranose ring glycosyl or a furanose ring glycosyl (R1 can be optionally arabinopyranosyl or rhamnopyranosyl);

[0170] R8 is

[0171] R4 is H or phenyl.

[0172] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ic); R1 is arabinopyranosyl or rhamnopyranosyl; R8 is R4 is H or phenyl.

[0173] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ic); the compound of formula (Ic) satisfies one, two or three of the following characteristics:

[0174] R1 is a pyranose ring glycosyl or a furanose ring glycosyl (R1 can be optionally arabinopyranosyl or rhamnopyranosyl);

[0175] R8 is

[0176] R4 is H or phenyl.

[0177] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ic); R1 is arabinopyranosyl or rhamnopyranosyl; R8 is R4 is H or phenyl.

[0178] In some embodiments, the triterpenoid compound of formula (I) is a compound of formula (Ic); R8 is R4 is H.

[0179] In some embodiments, the triterpenoid compound of formula (I) is any of the following compounds:

[0180]

[0181]

[0182]

[0183] In the present application, C1 to C15 compounds are also referred to as compounds 1 to 15, respectively.

[0184] C1 compound (Compound 1): is a compound of formula (Ia), wherein R1 is R7 is R8 is

[0185] Compound C2 (Compound 2): is a compound of formula (Ia), wherein R1 is R7 is R8 is

[0186] Compound C3 (Compound 3): is a compound of formula (Ib), wherein R4 is H, R8 is R a for

[0187] C4 compound (Compound 4): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is

[0188] Compound C5 (Compound 5): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is R b It is a methoxy group.

[0189] C6 compound (Compound 6): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is Rb It is a methoxy group.

[0190] C7 compound (Compound 7): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is R a For OH.

[0191] C8 compound (Compound 8): is a compound of formula (Ic), wherein R1 is (Right now ), R4 is H, R8 is

[0192] C9 compound (Compound 9): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is R b For OH.

[0193] Compound C10 (Compound 10): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is R b For OH.

[0194] C11 compound (Compound 11): is a compound of formula (Ic), wherein R1 is R4 is phenyl, R8 is

[0195] C12 compound (Compound 12): is a compound of formula (Ic), wherein R1 is R4 is methyl, R8 is

[0196] C13 compound (Compound 13): is a compound of formula (Ic), wherein R1 is R4 is ethyl, R8 is

[0197] C14 compound (Compound 14): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is

[0198] C15 compound (Compound 15): is a compound of formula (Ic), wherein R1 is R4 is H, R8 is

[0199] The triterpenoid compound of formula (I) can be isolated and purified from the natural plant Cyclocarya paliurus (such as compounds 1 to 10), and can also be obtained by optimizing the structure of the isolated triterpenoid compound (such as compounds 11 to 15). The triterpenoid compound of formula (I) has an active compound with a broader antibacterial spectrum, higher efficacy, better drugability and better safety, and can be used for the preparation of antibacterial drugs and antibacterial agents, and can be applied to the treatment of bacterial infections (including but not limited to drug-resistant bacterial infections). The pharmaceutically acceptable salts of the triterpenoid compound of formula (I) can be prepared by conventional salt-forming methods in the art, such as, but not limited to, cooling crystallization method, anti-solvent method, etc.

[0200] In traditional technology, Cyclocarya paliurus is believed to have the effects of clearing away heat and relieving summer heat, lowering blood sugar and blood pressure. Research in recent years has also focused on the hypoglycemic pharmacology and material basis of the efficacy of Cyclocarya paliurus. In this application, some triterpenoid compounds are obtained from the Cyclocarya paliurus leaf extract through a specific separation and purification method, and then new triterpenoid compounds are derived. The separation and purification method used in this application has a higher extraction efficiency.

[0201] After a lot of experimental exploration, the inventors of the present application unexpectedly discovered that the triterpenoid compounds of formula (I) have a strong killing effect on a variety of common pathogenic bacteria, such as: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Escherichia coli, Enterococcus faecalis, vancomycin-resistant Enterococcus, Pseudomonas aeruginosa, Mycobacterium abscessus, Klebsiella pneumoniae and Helicobacter pylori. The triterpenoid compounds of formula (I) still have high bactericidal activity against some antibiotic-resistant strains, such as: methicillin-gold-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus and linezolid-resistant Enterococcus.

[0202] The bactericidal concentration MIC of the triterpenoid compound of formula (I) for one or more of the above-mentioned bacteria can reach less than 150 μg / mL, further can reach less than or equal to 75 μg / mL, further can reach less than or equal to 37.5 μg / mL, and further can reach less than or equal to 9.375 μg / mL.

[0203] As a non-limiting example, for example, the MIC of compound 8 against alpha-hemolytic streptococci, beta-hemolytic streptococci, and Streptococcus pneumoniae may satisfy ≤9.375 μg / mL, the MIC against Staphylococcus aureus, MRSA, Staphylococcus epidermidis, and Escherichia coli may satisfy ≤18.75 μg / mL, the MIC against saprophytic Staphylococcus may satisfy ≤37.5 μg / mL, the MIC against Enterococcus faecalis, vancomycin-resistant Enterococci, and linezolid-resistant Enterococci may satisfy ≤75 μg / mL, and the MIC against Pseudomonas aeruginosa, Mycobacterium abscessus, Klebsiella pneumoniae, and Helicobacter pylori may satisfy ≤150 μg / mL.

[0204] In some embodiments, compound 8 and compound 11 can be used for applications targeting bacteria such as streptococci (such as group A / B hemolytic streptococci and streptococci pneumoniae) and staphylococci (such as methicillin-resistant / sensitive Staphylococcus aureus and Staphylococcus epidermidis). It can be used for skin and soft tissue infections, respiratory tract infections, heart valve infections, and bone and joint infections, but is not limited thereto. In some embodiments, compound 11 has a slightly stronger killing effect on staphylococci than compound 8.

[0205] In some embodiments, compound 14 has a killing effect on streptococci (such as A / B hemolytic streptococci and Streptococcus pneumoniae) and staphylococci (such as methicillin-resistant / sensitive Staphylococcus aureus and Staphylococcus epidermidis), and can also kill Bacillus (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Mycobacterium abscessus, Helicobacter pylori, etc.). The killing effect of compound 14 on Escherichia coli is stronger than that of compound 8 and compound 11. In addition, compound 14 also has a certain effect on Enterococcus faecalis, vancomycin-resistant Enterococcus and linezolid-resistant Enterococcus. Compound 14 can also be used for skin and soft tissue infections, respiratory tract infections, heart valve infections and bone and joint infections. In addition, it may also be suitable for digestive tract infections, bacteremia and other aspects.

[0206] In some embodiments, compound 15 can have a good effect on Streptococcus, Staphylococcus aureus, Bacillus and Enterococcus. Based on the above application examples of compound 14, compound 15 can also be used for urinary tract infection.

[0207] In some embodiments, relative to Lactobacillus acidophilus, the triterpenoid compounds of formula (I) show a certain selectivity in their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci and linezolid-resistant enterococci, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus.

[0208] In the present application, MIC (Minimal Inhibitory Concentration) can be used to characterize the antibacterial ability. The lower the MIC value, the lower the effective antibacterial concentration and the stronger the antibacterial effect. The triterpenoid compound of formula (I) in the present application can achieve antibacterial effect by targeting FtsZ.

[0209] The bacterial division Z ring is a ring structure formed by the filamentous temperature-sensitive mutant Z (FtsZ) at the cell division site. It is the basic structure for bacteria to survive and proliferate. Because it exists in most bacterial species, is highly conserved, and plays a decisive role in cell division, cell wall formation, cell morphology and structural stability, it can be used as a potential target for new antibiotics. Although a very small number of compounds that act on FtsZ have been successfully artificially produced, such as PC190723, there are no antibacterial drugs targeting FtsZ on the market worldwide due to poor drugability and high toxicity.

[0210] The triterpenoid compounds of formula (I) provided in the present application target FtsZ, occupy the binding domain of FtsZ and its active substrate guanosine triphosphate (GTP), hinder the binding of FtsZ and GTP, lead to GTP hydrolysis disorder, block the formation of Z ring, and make the cells after nucleic acid replication unable to complete division, and finally the bacteria rupture and die. Therefore, the triterpenoid compounds of formula (I) that can bind to the GTP site have antibacterial effects, and the antibacterial efficacy is positively correlated with its binding force. As a drug target that has not yet been clinically applied, bacteria have no resistance to drugs targeting FtsZ. The triterpenoid compounds of formula (I) have the efficacy of treating drug-resistant bacterial infections.

[0211] Mammalian cells do not secrete FtsZ. Therefore, it can be considered that the triterpenoid compounds of formula (I) have no known toxic side effects in the human body. In addition, the triterpenoid compounds of formula (I) are derived from natural plants that are both edible and medicinal, and have the advantage of good drugability.

[0212] The top and bottom structures of FtsZ protein have significant geometric complementarity. In the polymer state, a wide hydrophobic interaction area is formed between the bottom of FtsZ protein at the top (C-terminal domain) and the top of FtsZ protein at the bottom (N-terminal domain). The GTP binding domain in the FtsZ structure is composed of 85 carbon atoms, 24 nitrogen atoms and 27 oxygen atoms, forming a pocket-like structure. Its pocket volume is Has a surface area of Depth up to Theoretically, FtsZ has 17 donor units and 34 acceptor units that form hydrogen bonds, and 20 hydrophobic binding sites. The hydrophilic / hydrophobic ratio is 0.28. The schematic diagram of the binding pocket of FtsZ can be found in Figure 3 , where the light-colored part is the binding pocket area.

[0213] Molecular docking showed that the binding site of the triterpenoid compound of formula (I) may be in the GTP binding domain between the N-terminus and the H7 helix of FtsZ, and its binding mode may be similar to the reported crystal structure of the complex of FtsZ and GTP (PDBID: 5MN5).

[0214] Taking compound 8 and compound 11 as examples, Figure 1 and Figure 2 Schematic diagrams of the binding modes of compound 8 and compound 11 with FtsZ: Figure 1 In the figure, (A) is a visualization diagram of the docking of compound 8 and FtsZ, and (B) is a surface diagram of the interaction between compound 8 and FtsZ; Figure 2 In the figure, (A) is a visualization diagram of the docking of compound 11 and FtsZ, and (B) is the interaction surface diagram of compound 11 and FtsZ.

[0215] See also Figure 1 and Table 4, Molecular docking showed that compound 8 could deeply insert into the GTP binding pocket of FtsZ, and form hydrogen bonds with amino acid residues Gly108, Thy109, Glu139 and ASN166 of Ftsz protein to interact, bind to each other through hydrophobic interaction between amino acid residues Asp46, Pro135 and Phe183, and bind to each other through ionic bonds between amino acid residues Arg143. The analysis results showed that the docking index of compound 8 with FtsZ was -5.593, which was equivalent to the docking index of natural ligand GTP with FtsZ -5.612. It is speculated that compound 8 competitively binds to the GTP binding site of FtsZ, causing FtsZ to lose its GTPase activity and fail to catalyze GTP to form Z ring, which ultimately leads to bacterial death.

[0216] PC190723 is the most studied compound targeting FtsZ. The binding site of this compound is located in the gap formed by the H7 helix and the C-terminal domain, rather than directly interacting with the GTP binding domain of FtsZ. However, after compound 8 and PC19023 bind to FtsZ, the GTPase activity of FtsZ is inhibited. The difference between the triterpenoid compounds of formula (Ib), formula (Ic) and formula (Ia) is that the triterpenoid compounds of formula (Ib) and formula (Ic) are open-ring tetracyclic triterpenoid compounds, and the triterpenoid compounds of formula (Ia) are tetracyclic triterpenoid compounds with a complete structure. Among the compounds contained in the plant Cyclocarya paliurus, the open-ring tetracyclic triterpenoid compounds usually have carboxyl groups, contain active hydrogen, and are easy to form hydrogen bonds, which may help stabilize this binding and achieve better antibacterial effects.

[0217] It has been verified that the triterpenoid compound of formula (I) provided in the present application has a good FtsZ binding ability, which can be seen in the following examples.

[0218] In yet another aspect of the present application, a method for preparing a triterpenoid compound of formula (I) is provided.

[0219] In some embodiments, some triterpenoid compounds are extracted from Cyclocarya paliurus, such as compounds 1-10.

[0220] In some embodiments, some triterpenoid compounds are prepared based on triterpenoid compounds extracted from Cyclocarya paliurus by one or more derivatization methods such as esterification, acylation, alkylation, double bond addition reaction, etc., such as compounds 11-15.

[0221] The present application provides a method for separating and purifying triterpenoid compounds from Cyclocarya paliurus, and also provides a method for structural modification of the extracted triterpenoid compounds through chemical reactions. The following method 1 or method 2 may be used.

[0222] Method 1, separation and purification of triterpenoids from Cyclocarya paliurus: using 10 times the weight of ethanol to perform two reflux extractions on the shade-dried Cyclocarya paliurus leaves, combining the filtrates, concentrating and drying, mixing with silica gel, and then dry-loading on a silica gel column for gradient elution to obtain compounds, wherein the elution solvent can be selected from one or more of the following solvents: dichloromethane, methanol, water, petroleum ether and ethyl acetate. The triterpenoids obtained by method 1 can be recorded as "extract compounds".

[0223] Method 2: Based on the triterpenoids obtained in method 1, triterpenoids with other structures are obtained through conventional chemical reactions such as esterification, addition reaction, acylation, alkylation, etc. If necessary, a suitable hydroxyl protecting agent can be used to protect the hydroxyl group in the reaction.

[0224] The above-mentioned reagents for group modification of the extract compounds can be selected from one or more of the following: acetic anhydride, benzoyl chloride, trifluoroacetyl ester, benzyl ether, methanol, ethanol, propanol, isopropanol, n-butanol, tert-butanol, sec-butanol, isobutanol, cyclopropanol, cyclobutanol, cyclopentanol, cyclohexanol, acetyl chloride, dimethyl sulfate and benzyl chloride.

[0225] The triterpenoid compound of formula (I) can also be prepared based on other triterpenoid compounds through reaction.

[0226] The above-mentioned compounds provided in the present application can be derived from natural plants, and not only have high antibacterial efficacy and a broad antibacterial spectrum, but also have significant inhibitory and killing activity against a variety of antibiotic-resistant strains, and the effective dose MIC can reach the antibacterial level of some currently known synthetic antibiotics. In the first aspect of the present application, the use of a triterpenoid compound of formula (I) in the preparation of an antibacterial composition is provided.

[0227] In the present application, as described above, "antibacterial composition" refers to a composition having an antibacterial effect, which contains, in addition to the antibacterial component, a second component, which may be an antibacterial component or a non-antibacterial component.

[0228] In the present application, as described above, "antibacterial ingredient" refers to an ingredient with antibacterial effect; "non-antibacterial ingredient" refers to an ingredient without antibacterial effect. Non-antibacterial ingredients may have other physiological and / or pharmacological functions, and may also be excipients.

[0229] In the present application, as described above, whether a substance has an "antibacterial effect" refers to whether it has a killing effect on bacteria.

[0230] In the present application, a "composition" may be a combination of multiple substances, and further, may be used in combination, or may be a mixture of the combination.

[0231] In this application, "antimicrobial composition" refers to a composition with antimicrobial effect. "Antibacterial composition" can be used for medical purposes, but is not limited thereto, for example, it can also be used for daily cleaning products, cosmetics, etc., and can also be used to improve the antimicrobial ability of daily necessities, such as plastic products, etc.

[0232] Without limitation, the triterpenoid compounds of formula (I) and antibacterial compositions containing the same, in addition to their pharmaceutical uses, can also be used as functional materials in daily necessities, packaging supplies, household appliances, environmental materials, building materials and coatings, etc., non-limiting examples of which include antibacterial films, touch surfaces of electrical appliances, water treatment, sanitary ceramics, antibacterial coatings, etc.

[0233] As a non-limiting example, the triterpenoid compound of formula (I) and the antibacterial composition containing the same can also be used to prepare oral preparations, such as mouthwash, toothpaste, skin, mucosa, and lumen washing liquid.

[0234] As a non-limiting example, the triterpenoid compound of formula (I) and the antibacterial composition containing the same can be used in the field of animal husbandry, for example, it can be added to animal feed for the prevention of bacterial infection, and can also be used to prepare veterinary preparations for the treatment of bacterial infection. It should be understood that "excipients" can be selected from substances allowed to be added in relevant management specifications, and further, do not include substances prohibited from being added in relevant management specifications. Unless otherwise specified, relevant management specifications refer to the current specifications at the time of production.

[0235] In the second aspect of the present application, there is provided the use of a triterpene compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial pharmaceutical composition, wherein the triterpene compound of formula (I) is as defined in the first aspect of the present application; the antibacterial pharmaceutical composition comprises a triterpene compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0236] In the present application, "antibacterial pharmaceutical composition" refers to a pharmaceutical composition having an antibacterial effect.

[0237] In this application, "drug" includes any agent, compound, composition or mixture that provides a pharmacological effect in vivo or in vitro, and often provides a beneficial effect. The scope of the pharmacological effect of the "drug" in vivo is not particularly limited, and it can be a systemic effect or only a local effect. The activity of the "drug" is not particularly limited, and it can be an active substance that can interact with other substances, or it can be an inert substance that does not interact.

[0238] In this application, "pharmaceutical composition" refers to a composition that has the effect of preventing and treating diseases or symptoms, can be used as a medicine or can be used to prepare medicines. In this application, "pharmaceutical" refers to a pharmaceutical preparation that can be directly administered, which usually has a prescribed usage and dosage, consistent with the above definition.

[0239] As used herein, "pharmaceutically acceptable" refers to those ligands, materials, compositions, and / or dosage forms that are suitable for administration to a patient within the scope of sound medical judgment and commensurate with a reasonable benefit / risk ratio.

[0240] In this application, "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. As used herein, the phrase "pharmaceutically acceptable carrier" includes buffers, sterile water for injection, solvents, dispersion media, coatings, isotonic agents and absorption delaying agents, and the like, that are compatible with drug administration. Each carrier must be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients in the formulation and not harmful to the patient. Suitable examples include, but are not limited to, one or more of the following: (1) sugars such as lactose, glucose, and sucrose; (2) starches such as corn starch, potato starch, and substituted or unsubstituted β-cyclodextrins; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes; (9) oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, etc. olive oil, corn oil and soybean oil; (10) glycols such as propylene glycol; (11) polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffered saline; and (21) other non-toxic compatible substances used in pharmaceutical formulations.

[0241] In the present application, the "carrier" may include, but is not limited to, mannitol, sorbitol, sodium pyrosulfite, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, methionine, vitamin C, disodium ethylenediaminetetraacetate (disodium EDTA), calcium sodium EDTA, carbonates, acetates, phosphates of monovalent alkali metals or their aqueous solutions, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, oligofructose, dextran, glycine, starch, sucrose, dextrin (such as maltodextrin), lactose, mannitol, silicon derivatives, cellulose and its derivatives, alginate, gelatin, polyvinyl pyrrolidone, glycerol, Tween 80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, cyclodextrin, phospholipid materials, kaolin, talc, calcium stearate, and one or more of magnesium stearate.

[0242] It should be understood that "pharmaceutically acceptable carriers" can be selected from substances that are allowed to be added in relevant management regulations, and further, do not include substances that are prohibited from being added in relevant management regulations. If not specifically limited, relevant management regulations refer to the current regulations at the time of production.

[0243] In the third aspect of the present application, there is provided the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for preventing and treating bacterial infection, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application.

[0244] Based on any suitable manner of the present application, in some further embodiments, the bacterial infection includes a drug-resistant bacterial infection disease, and the drug-resistant bacterial infection disease includes a disease caused by infection with at least one of methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and linezolid-resistant Enterococcus.

[0245] In this application, "prevention" and "prevention and / or treatment" have the same meaning and can be used interchangeably. In this application, "prevention" includes aspects such as prevention, treatment, and adjuvant therapy. As used herein, "prevention" refers to alleviating, delaying progression, attenuating, preventing, or maintaining an existing disease or condition. "Prevention" also includes curing one or more symptoms of a disease or condition, preventing its development, or alleviating to a certain extent. Among them, as used herein, "treatment" refers to alleviating, delaying progression, attenuating, or maintaining an existing disease or condition, and treatment also includes curing one or more symptoms of a disease or condition, preventing its development, or alleviating to a certain extent.

[0246] In the fourth aspect of the present application, there is provided the use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial product, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application.

[0247] As a non-limiting example, the antibacterial product may include but is not limited to at least one of medicines, medical devices, daily necessities, cosmetics, packaging supplies, etc., and the daily necessities may include but are not limited to one or more of cleaning supplies, sanitary care supplies, bedding, kitchen utensils, dining utensils, toys, etc.

[0248] In the fifth aspect of the present application, there is provided a use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof as an antibacterial agent, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application.

[0249] In some embodiments, the use may be for therapeutic purposes.

[0250] In some embodiments, the application is for non-diagnostic and therapeutic purposes. For example, it can be used as a reference compound for antibacterial drug screening, and can also be used as a functional material in daily necessities, packaging supplies, household appliances, environmental materials, building materials and coatings, etc. It can also be used in antibacterial films, touch surfaces of electrical appliances, water treatment products, sanitary ceramics, antibacterial coatings and other materials or products.

[0251] In the sixth aspect of the present application, there is provided a use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof as an FtsZ protein inhibitor, wherein the triterpenoid compound of formula (I) is as defined in the first aspect of the present application.

[0252] In some embodiments, the use may be for therapeutic purposes.

[0253] In some embodiments, the use is for non-diagnostic and non-therapeutic purposes.

[0254] Based on any suitable method of the present application, in some further embodiments, the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof has a killing effect on any one, any two or all of methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and linezolid-resistant Enterococcus. In some further embodiments, the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof also has a killing effect on one, more or all of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus.

[0255] Based on any suitable method of the present application, in some further embodiments, the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof is used in any suitable form of any of the following groups:

[0256] Preparations shown in Group A: tablets, capsules, granules, pills, ointments, solutions, suspensions, emulsions and creams;

[0257] Preparations shown in Group B: oral solution, lozenge, injection, suppository, spray, drop, patch and tube feeding preparations;

[0258] The form shown in group C: surface coating of a solid product and dopant in a solid product, wherein the solid product at least includes a plastic product.

[0259] In yet another aspect of the present application, a method for treating a bacterial infection disease is provided.

[0260] Based on any suitable manner of the present application, in some further embodiments, the bacterial infection includes a drug-resistant bacterial infection disease, and the drug-resistant bacterial infection disease includes a disease caused by infection with at least one of methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and linezolid-resistant Enterococcus.

[0261] In some embodiments, the treatment method comprises administering to the subject a therapeutically effective amount of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof.

[0262] In the present application, "subject" is an animal, which may be a mammal, and may further be a human. The term "mammal" mainly refers to warm-blooded vertebrate mammals, including but not limited to: cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, mice (such as rats, mice), pigs, cattle, sheep, horses, humans, etc., and may preferably be primates, and may further be humans.

[0263] In some embodiments, the subject is a mammal.

[0264] In some embodiments, the subject may be a patient who has already suffered from a bacterial infection, or may be a person at risk of suffering from a bacterial infection, such as a person who has undergone or is about to undergo a surgical operation, a person with trauma, etc.

[0265] In some embodiments, the subject can be an animal in the animal husbandry field. As a non-limiting example, the triterpenoid compound of formula (I) and the antibacterial composition containing the same can be added to animal feed for the prevention of bacterial infection, and can also be used to prepare veterinary preparations for the treatment of bacterial infection.

[0266] In the present invention, "therapeutically effective amount" refers to the amount of active pharmaceutical ingredient that will cause a biological or medical response in an individual to a disease, disorder and / or symptom, for example, the amount of active pharmaceutical ingredient that brings a pharmacologically positive effect to an individual, wherein the pharmacologically positive effect includes but is not limited to reducing or inhibiting enzyme or protein activity or improving symptoms, alleviating symptoms, slowing or delaying disease progression or preventing disease, etc.

[0267] The administration method may include, but is not limited to, oral, rectal, parenteral (intravenous, intramuscular or subcutaneous) injection, topical administration, and inhalation. Taking the oral administration method as an example, the corresponding oral preparation may be, but is not limited to, oral preparations, such as mouthwash, toothpaste, skin, mucosa, lumen washing liquid, etc.

[0268] Some specific embodiments are provided below.

[0269] The embodiments of the present application will be described in detail below in conjunction with examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. The experimental methods for which specific conditions are not specified in the following examples are preferably referred to the guidance provided in the present application, and can also be based on the experimental manual or normal conditions in this area, can also be based on the conditions recommended by the manufacturer, or refer to experimental methods known in the art.

[0270] In the following specific embodiments, the measured parameters of raw material components may have slight deviations within the range of weighing accuracy unless otherwise specified. For temperature and time parameters, acceptable deviations caused by instrument test accuracy or operation accuracy are allowed.

[0271] Unless otherwise specified, the "room temperature" hereinafter refers to 20-30°C, and may further be 25°C.

[0272] Unless otherwise specified, "80% ethanol" means a mixed solvent in which ethanol accounts for 80% by volume and water accounts for 20% by volume.

[0273] Unless otherwise specified, when a solution is involved, if the solvent is not specified, the solvent is water. For example, "5% hydrochloric acid" means a hydrochloric acid aqueous solution with a weight percentage of HCl of 5%; "5% sodium bicarbonate" means a hydrochloric acid aqueous solution with a weight percentage of sodium bicarbonate of 5%.

[0274] If not otherwise specified, HOBt is 1-hydroxybenzotriazole, EDC is 1-ethyl-(3-dimethylaminopropyl)carbodiimide, DMAP is 4-dimethylaminopyridine, DIEA is diisopropylethanolamine, and DMSO is dimethyl sulfoxide.

[0275] 1. Preparation of triterpenoid compounds from Cyclocarya paliurus

[0276] (I) Extraction and preparation of triterpenoid compounds 1-10 from Cyclocarya paliurus

[0277] Weigh 5 kg of room temperature dried Cyclocarya paliurus leaves, crush them, add 10 times the weight of 80% ethanol, reflux and extract at 50°C for 1 hour, filter the residue and extract it again in the same way, combine the filtrates of the two extractions, concentrate and dry (300 g), mix with silica gel (100-200 mesh), and dry load on a 3000 g silica gel column, and elute with dichloromethane-methanol (90%-0%) gradient, i.e., gradient elution from dichloromethane:methanol volume ratio of 90%:10% to 0%:100%, the elution volume is 3 column volumes, and 6 fractions (Fr.1-6) are obtained. Fr.1 (55 g) was placed on an 800 g silica gel column and gradient eluted with petroleum ether-ethyl acetate (100%-20%, i.e., from petroleum ether:ethyl acetate volume ratio of 100%:0% to 20%:80%), with an elution volume of 3 column volumes, to obtain 5 fractions (Fr.1a-e). Fr.1b (2 g) was repeatedly subjected to C18 preparative chromatography with methanol-water (20%-100%, i.e., from methanol:water volume ratio of 20%:80% to 100%:0%) gradient elution, with an elution volume of 4 column volumes, to obtain compound 5 (208 mg) and compound 6 (112 mg). Fr.2 (62 g) was subjected to 800 g silica gel column, and gradient eluted with petroleum ether-ethyl acetate (80%-20%, i.e., from petroleum ether:ethyl acetate volume ratio of 80%:20% to 20%:80%), with an elution volume of 3 column volumes, to obtain 5 fractions (Fr.2a-e). Fr.2b (3 g) was repeatedly subjected to C18 preparative chromatography with methanol-water (20%-100%, i.e., from methanol:water volume ratio of 20%:80% to 100%:0%) gradient elution, with an elution volume of 4 column volumes, to obtain compound 7 (230 mg) and compound 8 (183 mg). Fr.3 (80 g) was subjected to 800 g silica gel column and gradient eluted with petroleum ether-ethyl acetate (80%-20%, i.e., from petroleum ether:ethyl acetate volume ratio of 80%:20% to 20%:80%) in a volume of 3 column volumes to obtain 4 fractions (Fr.3a-d). Fr.2c (2 g) was repeatedly subjected to C18 preparative chromatography with methanol-water (20%-100%, i.e., from methanol:water volume ratio of 20%:80% to 100%:0%) and gradient eluted in a volume of 4 column volumes to obtain compound 3 (106 mg), compound 4 (115 mg), compound 9 (95 mg) and compound 10 (150 mg). Fr.4 (30 g) was placed on a 300 g silica gel column and gradient eluted with petroleum ether-ethyl acetate (70%-10%, i.e., from petroleum ether:ethyl acetate volume ratio of 70%:30% to 10%:90%) in a volume of 3 column volumes to obtain 4 fractions (Fr.4a-d). The fractions were repeatedly subjected to preparative chromatography with methanol-water (20%-100%, i.e., from methanol:water volume ratio of 20%:80% to 100%:0%) and gradient eluted in a volume of 4 column volumes to obtain compound 1 (103 mg) and compound 2 (120 mg).

[0278] Each fraction can be analyzed by mass spectrometry (MS), H NMR ( 1 H NMR) and carbon NMR ( 13 C NMR) method can be used for structural identification, and other known structural analysis methods in the field of organic chemistry can also be combined. Taking compound 3 and compound 8 as examples, the following provides 1 H NMR and 13 C NMR test data.

[0279] Compound 1: 20,24-Epoxydammarane (-3β,12β,24R)-12-O-α-L-rhamnopyranosyl-25-hydroxy-3-O-α(-5′-O-acetyl)-L-furanoarabinoside.

[0280] Compound 2: Cyclocarya paliurus glycoside B: (20S, 24R)-epoxydammarane-(3β, 12β)-25-hydroxyl-12-O-β-D-quinovopyranosyl-3-O-β-D-quinovopyranoside ((20S, 24R)-epoxydammarane-(3β, 12β)-25-hydroxy-12-O-β-D-rhamnopyranosyl-3-O-β-D-rhamnopyranoside).

[0281] Compound 3: Cyclocarya paliurus glycoside II: (20S)-20-hydroxy-24-OaL-arabinopyranosyl-3,4-secodammar-4(28),11,25-trien-3-oic acid, white powder, easily soluble in organic solvents such as ethanol, methanol, acetonitrile, positive in Liebermann-Burchard reaction, MS m / z: 603.81 [MH] - , 1 HNMR (DMSO-d6, 400 MHz) and 13 CNMR (DMSO-d6, 100 MHz), the structural characterization parameters of compound 3 can be seen in Table 1.

[0282] Compound 4: Cyclocarya paliurus glycoside III: 25-hydroxy-(20S,24R)-epoxy-12R-O-β-o-quinovopyranosyl-3,4-secodammar-4(28)-en,3-oic acid (25-hydroxy-(20S,24R)-epoxy-12R-O-β-pyranosyl-3,4-didamar-4(28)-en,3-oic acid).

[0283] Compound 5: Cyclocarya paliurus glycoside D: (23E)-(12R,20S)-12,20-dihydroxy-25-methoxy-3,4-secodammara-4(28),23-dien-3-oic acid 12-O-β-D-quinovopyranoside ((23E)-(12R,20S)-12,20-dihydroxy-25-methoxy-3,4-didamara-4(28),23-dien-3-oic acid 12-O-β-D-rhamnopyranoside).

[0284] Compound 6: Cyclocarya paliurus glycoside F: (23E)-(12R,20S)-12,20-dihydroxy-25-methoxy-3,4-secodammara-4(28),23-dien-3-oic acid 12-O-α-Larabinopyranoside ((23E)-(12R,20S)-12,20-dihydroxy-25-methoxy-3,4-didamar-4(28),23-dien-3-oic acid 12-O-α-pyranoarabinoside).

[0285] Compound 7: Cyclocarya paliurus glycoside J: (12R,20S,24S)-20,24-dihydroxy-3,4-secodammara-2(28),25-dien-3-oic acid-12-OaL-arabinopyranoside ((12R,20S,4S)-20,24-dihydroxy-3,4-didamar-2(28),25-dien-3-oic acid 12-O-α-L-arabinopyranoside).

[0286] Compound 8: Cyclocarya paliurus glycoside K: (23E)-(12R,20S)-20-hydroxy-3,4-secodammarane-4(28),23,25-trien-3-oic acid-12-ObD-quinovopyranoside ((23E)-(12R,20S)-20-hydroxy-3,4-didamarane-4(28),23,25-trien-3-oic acid-12-O-β-D-rhamnopyranoside), white powder, easily soluble in organic solvents such as ethanol, methanol, acetonitrile, Liebermann-Burchard reaction positive, MS m / z: 617.55 [MH] - , 1 HNMR (DMSO-d6, 400 MHz) and 13 C NMR (DMSO-d6, 100 MHz), the structural characterization parameters of compound 8 can be seen in Table 1.

[0287] Compound 9: Diecatin A: (23E)-(12R,20S)-12,20,25-trihydroxy-3,4-secodammara-4(28),23-dien-3-oic acid 12-O-β-D-quinovopyranoside ((23E)-(12R,20S)-12,20,25-trihydroxy-3,4-didamar-4(28),23-dien-3-oic acid 12-O-β-D-rhamnopyranoside).

[0288] Compound 10: Diecatin B: (23E)-(12R,20S)-12,20,25-trihydroxy-3,4-secodammara-4(28),23-dien-3-oic acid12-O-α-L-arabinopyranoside ((23E)-(12R,20S)-12,20,25-trihydroxy-3,4-didamar-4(28),23-dien-3-oic acid12-O-α-L-arabinopyranoside).

[0289] Table 1. Compound 3 and Compound 8 1 H NMR and 13 C NMR data

[0290]

[0291]

[0292] (II) Synthesis and preparation of compound 11

[0293] In an ice-water bath, compound 8 (6 mg, 10 μmol, 1 molar equivalent) and benzyl alcohol (1 mg, 10 μmol) were added to 2 mL of dichloromethane, followed by HOBt (1.8 mg, 13 μmol) and EDC (2.5 mg, 13 μmol), and 2-3 times the molar equivalent of DMAP or DIEA were added as appropriate. The reaction was allowed to proceed for about 10 h at room temperature, and the reaction was monitored by thin layer chromatography (TLC). After the reaction was completed, the mixture was washed three times with 5 mL of 5% hydrochloric acid, three times with 5 mL of 5% sodium bicarbonate, three times with 10 mL of water, and three times with 10 mL of saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography (dichloromethane / methanol mixed solvent, volume ratio of 100:1 to 10:1) to obtain 6.5 mg of product (compound 11) with a yield of 93.5%.

[0294]

[0295] 1 H-NMR, 13 C-NMR, MS [M+H] + Characterization results:

[0296] MS m / z:695.4441[M+H] + .

[0297] 1 H-NMR (400MHz, DMSO-d6) δ: 7.33(m,5H),6.13(d,1H),5.74(dt,1H),5.21(s,2H),4.88(s,2H),4.82(s,1H) ,4.65(s,1H),4.36(d,1H),4.12(dt,1H),3.91(dd,2H),3.71(s,1H),3.60(m,1H),3.26(m,2H),3.17(m,1H) ,2.58(td,1H),2.20(m,1H),2.11(m,2H),2.33(dd,1H),1.98(dd,1H),1.80(s,3H),1.78(d,1H),1.71(s,3H ),1.61(m,2H),1.49(m,2H),1.27(m,2H),1.14(s,3H),1.10(m,2H),1.05(s,3H),0.98(s,3H),0.96(s,3H).

[0298] 13C-NMR (100MHz, DMSO-d6) δ: 176.65, 148.25, 142.09, 136.11, 134.83, 128.93, 128.1 9,127.63,127.12,115.05,113.68,100.21,74.87,73.88,73.26,71.39,68.61,66. 84,66.44,51.19,50.51,49.49,49.04,44.56,43.98,40.52,36.86,34.73,32.84,30.92,29.69,27.14,25.99,24.93,24.14,20.20,19.04,18.36,16.69,16.65,15.68.

[0299] (III) Synthesis and preparation of compound 12

[0300] In an ice-water bath, compound 8 (6 mg, 10 μmol, 1 molar equivalent) and methanol (0.3 mg, 10 μmol) were added to 2 mL of dichloromethane, followed by HOBt (1.8 mg, 13 μmol) and EDC (2.5 mg, 13 μmol), and 2-3 times the molar equivalent of DMAP or DIEA were added as appropriate. The reaction was allowed to proceed for about 10 h at room temperature, and the reaction was monitored by TLC. After the reaction was completed, the mixture was washed three times with 5 mL of 5% hydrochloric acid, three times with 5 mL of 5% sodium bicarbonate, three times with 10 mL of water, and three times with 10 mL of saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography (dichloromethane / methanol mixed solvent, volume ratio of 100:1 to 10:1) to obtain 6.0 mg of product (compound 12) with a yield of 94.8%.

[0301]

[0302] 1 H-NMR, 13 C-NMR, MS [M+H] + Characterization results:

[0303] MS m / z:633.4291[M+H] + .

[0304] 1H-NMR (400MHz, DMSO-d6) δ: 6.13(d,1H),5.74(dt,1H),5.21(s,2H),4.88(s,2H),4.82(s,1H),4.65(s,1H) ,4.36(d,1H),4.12(dt,1H),3.91(dd,2H),3.71(s,1H),3.64(s,3H),3.60(m,1H),3.26(m,2H),3.17(m,1H) ,2.58(td,1H),2.20(m,1H),2.11(m,2H),2.33(dd,1H),1.98(dd,1H),1.80(s,3H),1.78(d,1H),1.71(s,3H ),1.61(m,2H),1.49(m,2H),1.27(m,2H),1.14(s,3H),1.10(m,2H),1.05(s,3H),0.98(s,3H),0.96(s,3H).

[0305] 13 C-NMR (100MHz, DMSO-d6) δ: 176.65, 148.25, 142.09, 134.83, 128.93, 115.05 ,113.68,100.21,74.87,73.88,73.26,71.39,68.61,66.84,66.44,51.91,51 .19,50.51,49.49,49.04,44.56,43.98,40.52,36.86,34.73,32.84,30.92,29.69,27.14,25.99,24.93,24.14,20.20,19.04,18.36,16.69,16.65,15.68.

[0306] (IV) Synthesis and preparation of compound 13

[0307] In an ice-water bath, compound 8 (6 mg, 10 μmol, 1 molar equivalent) and ethanol (0.45 mg, 10 μmol) were added to 2 mL of dichloromethane, followed by HOBt (1.8 mg, 13 μmol) and EDC (2.5 mg, 13 μmol), and 2-3 times the molar equivalent of DMAP or DIEA were added as appropriate. The reaction was allowed to proceed for about 10 h at room temperature, and the reaction was monitored by TLC. After the reaction was completed, the mixture was washed three times with 5 mL of 5% hydrochloric acid, three times with 5 mL of 5% sodium bicarbonate, three times with 10 mL of water, and three times with 10 mL of saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography (dichloromethane / methanol mixed solvent, volume ratio of 100:1 to 10:1) to obtain 6.1 mg of product (compound 13) with a yield of 94.3%.

[0308]

[0309] 1 H-NMR, 13 C-NMR, MS [M+H] + Characterization results:

[0310] MS m / z:647.4448[M+H] + .

[0311] 1 H-NMR (400MHz, DMSO-d6) δ: 6.13(d,1H),5.74(dt,1H),5.21(s,2H),4.88(s,2H),4.82(s,1H),4.65(s,1H),4. 36(d,1H),4.12(dt,1H),4.02(q,2H),3.91(dd,2H),3.71(s,1H),3.60(m,1H),3.26(m,2H),3.17(m,1H),2.58( td,1H),2.20(m,1H),2.11(m,2H),2.33(dd,1H),1.98(dd,1H),1.80(s,3H),1.78(d,1H),1.71(s,3H),1.61(m ,2H),1.49(m,2H),1.27(m,2H),1.14(s,3H),1.10(m,2H),1.08(t,3H),1.05(s,3H),0.98(s,3H),0.96(s,3H).

[0312] 13 C-NMR (100MHz, DMSO-d6) δ: 176.65,148.25,142.09,134.83,128.93,115.05,1 13.68,100.21,74.87,73.88,73.26,71.39,68.61,66.84,66.44,61.34,51.19 ,50.51,49.49,49.04,44.56,43.98,40.52,36.86,34.73,32.84,30.92,29.69,27.14,25.99,24.93,24.14,20.20,19.04,18.36,16.69,16.65,15.68,14.18.

[0313] (V) Synthesis and preparation of compound 14

[0314] Compound 8 (6 mg, 10 μmol) and isopentene (0.70 mg, 10 μmol) were added to 1 mL of dichloromethane and dissolved; 10 μL of dimethylaluminum chloride (1.0 M, 10 μmol) was slowly added to the reaction solution at 0°C. The reaction was carried out for about 10 hours at 0°C, and the reaction was quenched with water. After the reaction was completed, 3 mL of ether was used for extraction three times, and the organic phases were combined. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography (mixed solvent of n-hexane / ethyl acetate, volume ratio of 50:1 to 10:1) to obtain 5.2 mg of product (compound 14) with a yield of 75.4%.

[0315]

[0316] 1 H-NMR, 13 C-NMR, MS [M+H] + Characterization results:

[0317] MS m / z:689.4917[M+H] + .

[0318] 1 H-NMR (400MHz, DMSO-d6) δ: 5.37(d,1H),5.21(s,2H),4.82(s,1H),4.65(s,1H),4.36(d,1H),4.12(dt,1H),3.91( dd,2H),3.71(s,1H),3.60(m,1H),3.26(m,2H),3.17(m,1H),2.58(td,1H),2.20(m,1H),2.11(m,2H),2.33(dd,1H ),2.02(d,2H),1.98(dd,1H),1.78(d,1H),1.71(s,3H),1.67(d,2H),1.65(s,3H),1.61(m,2H),1.49(m,2H),1.45 (q,1H),1.41(m,1H),1.27(m,2H),1.14(s,3H),1.10(m,2H),1.05(s,3H),0.98(s,3H),0.96(s,3H),0.83(d,6H).

[0319] 13C-NMR (100MHz, DMSO-d6) δ: 176.65,148.25,131.12,124.26,100.21,74.87,73.8 8,73.26,71.39,68.61,66.84,66.44,51.19,50.51,49.49,49.04,44.56,43.98,4 0.52,37.31,36.86,36.63,35.47,34.73,32.84,32.75,30.92,29.69,27.14,26.43,25.99,24.93,24.14,22.69,21.11,21.11,20.20,18.36,16.69,16.65,15.68.

[0320] (VI) Synthesis and preparation of compound 15

[0321] Compound 8 (6 mg, 10 μmol) and vinyl methyl ketone (0.70 mg, 10 μmol) were added to 1 mL of dichloromethane and dissolved; 10 μL of dimethylaluminum chloride (1.0 M, 10 μmol) was slowly added to the reaction solution at 0°C. The reaction was carried out for about 10 hours at 0°C, and the reaction was quenched with water. After the reaction was completed, 3 mL of ether was used for extraction three times, and the organic phases were combined. The organic phase was dried over anhydrous sodium sulfate and purified by column chromatography (mixed solvent of n-hexane / ethyl acetate, volume ratio of 50:1 to 10:1) to obtain 5.3 mg of product (compound 15) with a yield of 76.8%.

[0322]

[0323] 1 H-NMR, 13 C-NMR, MS [M+H] + Characterization results:

[0324] MS m / z:689.4552[M+H] + .

[0325] 1H-NMR (400MHz, DMSO-d6) δ: 5.37(d,1H),5.21(s,2H),4.82(s,1H),4.65(s,1H),4.36(d,1H),4.12(dt,1H),3. 91(dd,2H),3.71(s,1H),3.60(m,1H),3.26(m,2H),3.17(m,1H),2.58(td,1H),2.20(m,1H),2.11(m,2H),2.33 (dd,1H),2.22(d,2H),1.98(dd,1H),1.96(s,3H),1.95(d,2H),1.78(d,1H),1.71(s,3H),1.65(s,3H),1.61(m ,2H),1.49(m,2H),1.45(t,1H),1.27(m,2H),1.14(s,3H),1.10(m,2H),1.05(s,3H),0.98(s,3H),0.96(s,3H).

[0326] 13 C-NMR (100MHz, DMSO-d6) δ: 209.51,176.65,148.25,133.12,124.26,100.21,74 .87,73.88,73.26,71.39,68.61,66.84,66.44,51.19,50.51,49.49,49.43,49. 04,44.56,43.98,40.52,36.86,34.73,34.84,32.84,32.55,30.92,30.72,29.69,27.14,25.99,25.63,24.93,24.14,22.67,20.20,18.36,16.69,16.65,15.68.

[0327] Test on the killing effect of diterpenoids and triterpenoids on bacteria

[0328] 1. Strains and drugs

[0329] Strains: Vancomycin-resistant Enterococci (VRE), Linezolid-resistant Enterococci, Methicillin-resistant Staphylococcus aureus Aureus, MRSA), Mycobacterium abscessus, Helicobacter pylori and Klebsiella pneumoniae were all isolated from West China Hospital of Sichuan University and provided by the Clinical Microbiology Laboratory: MRSA-1 (clinical number: 1911101191), MRSA-2 (clinical number: 1911081137), MRSA-3 (clinical number: 1911051296), MRSA-4 (clinical number: 1911051125), MRSA-5 (clinical number: 1911081165), VRE (clinical number: 2210251065), linezolid-resistant Enterococcus (2207221285), Klebsiella pneumoniae (2208181356) and Helicobacter pylori (2206222518). Common Staphylococcus aureus (ATCC25923), Escherichia coli ATCC25922, Staphylococcus epidermidis ATCC8099, Staphylococcus saprophyticus, Streptococcus pneumoniae ATCC6303, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Lactobacillus acidophilus ATCC4356, Enterococcus faecalis ATCC BAA-1240, Mycobacterium abscessus and Pseudomonas aeruginosa PA14 were all purchased.

[0330] Drugs: the triterpenoid compounds (compounds 1 to 15) prepared above, penicillin sodium, oxacillin sodium and vancomycin hydrochloride (purchased from the market).

[0331] (II) Bacterial culture

[0332] Culture medium: The culture medium for common Staphylococcus aureus (ATCC25923), MRSA-1, MRSA-2, MRSA-3, MRSA-4, MRSA-5, Staphylococcus epidermidis, Staphylococcus saprophyticus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae is MHB (Mueller-Hinton Broth). Streptococcus pneumoniae, alpha-hemolytic streptococci and beta-hemolytic streptococci are cultured in MHB medium containing 5% serum. Lactobacillus acidophilus ATCC4356 is cultured in MRS medium. Enterococcus faecalis, vancomycin-resistant enterococci and linezolid-resistant enterococci are cultured in trypticase soy broth medium containing 0.6% yeast extract. Culture conditions: 37°C, 150rpm shaking culture. Helicobacter pylori is cultured in Helicobacter pylori medium at 37°C in an incubator containing 5% O2, 5% CO2. Mycobacterium abscessus is cultured in Roche basal medium at 30°C.

[0333] (III) Test on the bactericidal effect of triterpenoids

[0334] Preparation of test bacteria: inoculate each bacterium in 5 mL of the corresponding culture medium, culture overnight at 37°C in a shaking incubator, adjust the McFarland turbidity of the bacterial solution to 0.5 McFarland units, and then dilute the bacterial solution 100 times for later use. The final bacterial concentration is 5×10 5 cfu / mL.

[0335] Preparation of triterpenoid mother solution: Accurately weigh 7.5 mg of triterpenoid powder and dissolve it in 1 mL of DMSO to obtain 7.5 mg / mL triterpenoid mother solution.

[0336] Preparation of triterpenoid drug concentration gradient: Take the drug mother solution and dilute it with the corresponding culture medium so that the initial concentration of triterpenoid compounds is 300μg / mL, take 100μL of the above drug solution and add it to the 1st and 2nd wells of the 96-well plate. From the 2nd well, add 100μL of culture medium and dilute it to the 9th well in a continuous manner. Set the 10th well as the culture medium control. From the 1st to the 9th well, the concentrations of triterpenoid compounds are 150μg / mL, 75μg / mL, 37.5μg / mL, 18.75μg / mL, 9.375μg / mL, 4.6875μg / mL, 2.34375μg / mL, 1.171875μg / mL, and 0.5859375μg / mL, respectively.

[0337] Test of antibacterial effect: Add 100 μL of the bacterial solution prepared above to the wells with each concentration of triterpenoid compounds and the wells with culture medium control. After thorough mixing, incubate in a humidified box at 37°C overnight. The test value of the lowest drug concentration with no colony growth is determined as MIC (minimum inhibitory concentration).

[0338] If none of the above concentrations can achieve “no colony growth”, the MIC will be recorded as “>150 μg / mL”.

[0339] MIC can be used to characterize antibacterial ability. The lower the MIC value, the lower the effective antibacterial concentration and the stronger the antibacterial effect.

[0340] The test results can be found in Table 2-3.

[0341] (IV) Test results

[0342] According to Table 2 and Table 3, it can be seen that these triterpenoids not only have a killing effect on the standard strain of common Staphylococcus aureus (ATCC25923), but also have a significant killing effect on various MRSA strains. In addition, triterpenoids also have a good killing effect on Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Escherichia coli, Enterococcus faecalis, vancomycin-resistant Enterococcus, linezolid-resistant Enterococcus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus.

[0343] Table 2. MIC test values ​​of triterpenoids against various bacteria (μg / mL)

[0344] strain 1 3 5 7 8 9 ATCC25923 75 37.5 37.5 37.5 18.75 37.5 MRSA-1 75 37.5 37.5 37.5 18.75 37.5 MRSA-2 75 37.5 37.5 37.5 18.75 37.5 MRSA-3 75 37.5 37.5 37.5 18.75 37.5 MRSA-4 75 37.5 37.5 37.5 18.75 37.5 MRSA-5 75 37.5 37.5 37.5 18.75 37.5 Grapefruit epidermis 75 37.5 37.5 37.5 18.75 37.5 Staphylococcus saprophyticus 75 37.5 37.5 37.5 37.5 37.5 Lactobacillus acidophilus >150 >150 >150 >150 >150 >150 Alpha-hemolytic Streptococcus 75 37.5 37.5 37.5 9.375 37.5 Beta-hemolytic Streptococcus 75 37.5 37.5 37.5 9.375 37.5 Streptococcus pneumoniae 75 37.5 37.5 37.5 9.375 37.5 Escherichia coli 150 75 37.5 75 18.75 75 Enterococcus faecalis 150 75 37.5 75 75 75 Vancomycin-resistant Enterococci 150 75 37.5 75 75 75 Linezolid-resistant Enterococci 150 75 37.5 75 75 75 Pseudomonas aeruginosa >150 150 150 150 150 150 Klebsiella pneumoniae >150 150 150 150 150 150 Mycobacterium abscessus >150 150 150 150 150 150 Helicobacter pylori >150 150 150 150 150 150

[0345] Table 3. MIC test values ​​of triterpenoids against various bacteria (μg / mL)

[0346] strain 10 11 12 13 14 15 ATCC25923 75 9.375 75 75 18.75 9.375 MRSA-1 75 9.375 75 75 18.75 9.375 MRSA-2 75 9.375 75 75 18.75 9.375 MRSA-3 75 9.375 75 75 18.75 9.375 MRSA-4 75 9.375 75 75 18.75 9.375 MRSA-5 75 9.375 75 75 18.75 9.375 Grapefruit epidermis 75 9.375 75 75 18.75 9.375 Staphylococcus saprophyticus 75 37.5 75 75 37.5 37.5 Lactobacillus acidophilus >150 >150 >150 >150 >150 >150 Alpha-hemolytic Streptococcus 75 9.375 75 75 9.375 9.375 Beta-hemolytic Streptococcus 75 9.375 75 75 9.375 9.375 Streptococcus pneumoniae 75 9.375 75 75 9.375 9.375 Escherichia coli 150 18.75 75 75 18.75 18.75 Enterococcus faecalis 150 75 150 150 37.5 18.75 Vancomycin-resistant Enterococci 150 75 150 150 37.5 18.75 Linezolid-resistant Enterococci 150 75 150 150 37.5 18.75 Pseudomonas aeruginosa >150 75 >150 >150 37.5 18.75 Klebsiella pneumoniae >150 75 >150 >150 37.5 18.75 Mycobacterium abscessus >150 75 >150 >150 37.5 18.75 Helicobacter pylori >150 75 >150 >150 37.5 18.75

[0347] In summary, these triterpenoids have strong killing effects on Escherichia coli, Staphylococcus aureus (such as ATCC25923), Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Enterococcus faecalis, methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, linezolid-resistant Enterococcus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus. As a non-limiting example, the minimum inhibitory concentration (MIC) of compounds 1-15 is less than or equal to 150 μg / mL, part is less than or equal to 37.5 μg / mL, and part is less than or equal to 9.375 μg / mL. In addition, relative to Lactobacillus acidophilus, each triterpenoid compound shows a certain selectivity.

[0348] Analysis of the antibacterial mechanism of diterpenoids and triterpenoids

[0349] Analysis method: The two-dimensional molecular formula of the triterpenoid compound of formula (I) was drawn in ChemDraw 18.0 software and exported as a .sdf format structure as a ligand. The FtsZ / GTP complex structure was used as a template, and the X-ray crystal structure of the complex was obtained from the PDB database (PDB ID: 5MN5). Molecular docking was performed using Schrödinger Glide in the software package was performed in its SP mode, LigPrep was used to pre-treat the ligand compounds under default parameters, and Proteinpreparation was used to pre-treat the protein complexes. After docking, the obtained docking results were analyzed using PyMol software.

[0350] The "docking score" of each compound and FtsZ is used to characterize the binding strength of the compound and FtsZ. The larger the negative value of the docking score, the stronger the binding strength of the compound and FtsZ.

[0351] The test results can be found in Table 4.

[0352] The docking score of compound 15 has the largest negative value, indicating that it has the strongest binding force with FtsZ and relatively stronger killing effect on various bacteria, which is consistent with the test results in Tables 2 and 3. This may be because compound 15 has a carboxyl group, and when the electron-withdrawing group keto carbonyl is introduced into R8, compound 15 can form hydrogen bond interactions with Gly110 and Asn44 of the GTP binding domain of FtsZ, making compound 15 have a stronger binding force with FtsZ.

[0353] For compound 1, the binding force between compound 1 and FtsZ may be weaker due to the larger molecular radius of compound 1, which increases the steric hindrance with the GTP binding domain of FtsZ and weakens the binding strength between the molecule and the binding domain.

[0354] The binding force between compound 12 and FtsZ is relatively weak, which may be due to the fact that R4 is an ester carbonyl group, the active hydrogen disappears, and hydrogen bonds cannot be formed.

[0355] Table 4. Molecular docking results (binding strength)

[0356] Triterpenoids Docking score Compound 1 -2.156 Compound 3 -4.938 Compound 5 -5.056 Compound 7 -4.982 Compound 8 -5.593 Compound 9 -4.966 Compound 10 -3.265 Compound 11 -6.841 Compound 12 -2.263 Compound 13 -2.569 Compound 14 -6.015 Compound 15 -7.223

[0357] The technical features of the above-mentioned embodiments and examples can be combined in any appropriate manner. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0358] The above embodiments only express several implementation methods of the present application, which is convenient for understanding the technical solution of the present application in detail, but it cannot be understood as limiting the scope of protection of the present application. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several deformations and improvements can be made, which all belong to the scope of protection of the present application. In addition, it should be understood that after reading the above teaching content of the present application, the technicians in this field can make various changes or modifications to the present application, and the equivalent forms obtained also fall within the scope of protection of the present application. It should also be understood that the technical solutions obtained by the technicians in this field through logical analysis, reasoning or limited experiments on the basis of the technical solutions provided in the present application are all within the scope of protection of the claims attached to the present application. Therefore, the scope of protection of the patent of this application shall be based on the content of the attached claims, and the description and drawings can be used to explain the content of the claims.

Claims

1. Use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial composition, in, is -CH=CH- or -CH2-CHR1-; R1 is selected from any one of a pyranose ring group, a furanose ring group, and any one of the aforementioned groups in which one -OH is acetylated; R2 is -(CH2)2-C(=O)-O-R4, R3 is -CH(=CH2)-CH3, or R2 and R3 are both -(CR5R6)2- and R2, R3 and adjacent carbon atoms form a 6-membered saturated ring, and any R5 and any R6 are independently H, methyl or -OR7; R4 and any one of R7 are independently selected from H, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 3-6 heterocycloalkyl and substituted or unsubstituted phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of heteroatoms X1 in the heterocycloalkyl group is one or more; 1-6 Alkyl, substituted C 3-6 Cycloalkyl, substituted C 3-6 In heterocycloalkyl and substituted phenyl, C1-6 alkyl, C 3-6 Cycloalkyl, C 3-6 The heterocycloalkyl and phenyl groups are independently substituted by one or more Q1 groups, any of which is independently selected from -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[O-divalent C 5-6 Heterocycloalkyl] n -OH, wherein the substituted -O-divalent C 5-6 The heterocycloalkyl-OH is substituted by one or more Q2, any Q2 is independently -CH3 or -OH, -CH3 and -OH are in the -O-divalent C 5-6 The number of all Q2 in heterocycloalkyl-OH is independently 1 to 4, and the divalent C 5-6 The ring atoms in the heterocycloalkyl group include heteroatoms X2, wherein the heteroatoms X2 are selected from O and N, divalent C 5-6 The number of the heteroatom X2 in the heterocycloalkyl group is one or more, and n is 0, 1, 2, 3, 4 or 5; R8 is selected from: Where R a and R b are independently selected from H, -OH, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 1-6 Alkyl-O-, substituted or unsubstituted C 3-6 Cycloalkyl-O- and substituted or unsubstituted C 3-6 Heterocycloalkyl-O-, wherein the substituted C 1-6 Alkyl, substituted C 1-6 Alkyl-O-, substituted C 3-6 Cycloalkyl-O- and substituted C 3-6 Heterocycloalkyl-O-, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O- and C 3-6 The heterocycloalkyl-O- is independently substituted by one or more Q3, any Q3 being independently selected from: -OH, methyl, ethyl, acetyl, methoxy, ethoxy, -F, -Cl and -Br; C 3-6 The ring atoms in the heterocycloalkyl group include a heteroatom X3, and the heteroatom X3 is selected from O and N.

2. The use according to claim 1, characterized in that: The triterpenoid compound of formula (I) is a compound of formula (II) or a compound of formula (III):

3. The use according to claim 1, characterized in that: R1 is selected from and any of the aforementioned groups in which one -OH group is acetylated.

4. The use according to any one of claims 1 to 3, characterized in that: R4 is H, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl or phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of the heteroatom X1 in the heterocycloalkyl group is one or two; Any R7 is independently selected from H, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 3-6 heterocycloalkyl and substituted or unsubstituted phenyl; wherein C 3-6 The ring atoms in the heterocycloalkyl group include heteroatoms X1, wherein the heteroatoms X1 is selected from O and N, C 3-6 The number of heteroatoms X1 in the heterocycloalkyl group is one or more; wherein the substituted C 1-6 Alkyl, substituted C 3-6 Cycloalkyl, substituted C 3-6 In heterocycloalkyl and substituted phenyl groups, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 3-6 The heterocycloalkyl and phenyl groups are independently substituted by one or more Q1, any Q1 being independently selected from -OH, -F, -Cl, -Br, -NH2, -NO2, acetyl, acetoxymethyl, C 1-6 Alkyl, C 1-6 Alkyl-O-, C 3-6 Cycloalkyl-O-, and substituted or unsubstituted-[OZ] n -OH, wherein -OZ- is a divalent pyranose ring group or a divalent furanose ring group, Z contains -OH, and n is 1, 2, 3, 4 or 5. When n is greater than 1, adjacent -OZ- are connected by glycosidic bonds.

5. The use according to claim 1, characterized in that: The triterpenoid compound of formula (I) is a compound of formula (Ia), a compound of formula (Ib) or a compound of formula (Ic); 6. The use according to any one of claims 1 to 5, characterized in that: Any C 1-6 Alkyl is independently methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl; Any C 3-6 Cycloalkyl is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; Any C 3-6 Heterocycloalkyl is independently oxirane, tetrahydropyranyl or tetrahydrofuranyl; Any bivalent C 5-6 The heterocycloalkyl groups are independently divalent tetrahydropyranyl or divalent tetrahydrofuranyl.

7. The use according to claim 6, characterized in that: Substituted or unsubstituted C 3-6 Heterocycloalkyl is Or a group in which one -OH in any of the aforementioned groups is acetylated.

8. The use according to claim 7, characterized in that: Substituted or unsubstituted C 3-6 Heterocycloalkyl is 9. The use according to claim 5, characterized in that: The triterpenoid compound of formula (I) is a compound of formula (Ib) or a compound of formula (Ic), wherein R4 is H, C 1-3 Alkyl or phenyl.

10. The use according to claim 9, characterized in that: R4 is H.

11. The use according to claim 5, characterized in that: The triterpenoid compound of formula (I) is a compound of formula (Ia) or a compound of formula (Ic), and R1 is a pyranose ring group or a furanose ring group.

12. The use according to claim 11, characterized in that: R1 is arabinopyranosyl or rhamnopyranosyl.

13. The use according to claim 12, characterized in that: R1 is 14. The use according to claim 5, characterized in that: In R8, R a and R b are independently H, -OH, C 1-3 Alkyl-O-, pyranose ring type glycosyl or furanose ring type glycosyl.

15. The use according to claim 14, characterized in that: In R8, R a and R b are each independently H, -OH, methoxy or α-L-arabinopyranosyl.

16. The use according to claim 14, characterized in that The triterpenoid compound of formula (I) is a compound of formula (Ic); In R8, R a and R b are each independently H, -OH or methoxy.

17. The use according to claim 5, characterized in that: R7 is H, arabinopyranosyl, arabinopyranosyl in which one hydroxyl group is acetylated, arabinofuranosyl, arabinofuranosyl in which one hydroxyl group is acetylated, rhamnopyranosyl, or rhamnopyranosyl in which one hydroxyl group is acetylated.

18. The use according to claim 17, characterized in that R7 is 19. The use according to claim 5, characterized in that: (Ia) In the compound, R1 is R7 is R8 is (Ib) wherein R4 is H, methyl, ethyl or phenyl, and R8 is R a for (Ic) In the compound, R1 is R4 is H, methyl, ethyl or phenyl, R8 is 20. The use according to any one of claims 1-5, 7-12, 14-16, characterized in that: The triterpenoid compound of formula (I) is compound (Ic), R1 is arabinopyranosyl or rhamnopyranosyl, R4 is H or phenyl, and R8 is 21. The use according to claim 20, characterized in that R1 is 22. The use according to any one of claims 1-5, 9, 11, 14-16, characterized in that: The triterpenoid compound of formula (I) is a compound of formula (Ic); the compound of formula (Ic) satisfies one, two or three of the following characteristics: R1 is a pyranose ring or furanose ring; R8 is R4 is H or phenyl.

23. The use according to claim 22, characterized in that R1 is arabinopyranosyl or rhamnopyranosyl; R8 is R4 is H or phenyl.

24. The use according to any one of claims 1-5, 9, 11, 14-16, characterized in that: The triterpenoid compound of formula (I) is a compound of formula (Ic); the compound of formula (Ic) satisfies one, two or three of the following characteristics: R1 is a pyranose ring or furanose ring; R8 is R4 is H or phenyl.

25. The use according to claim 24, characterized in that R1 is arabinopyranosyl or rhamnopyranosyl; R8 is R4 is H or phenyl.

26. The use according to claim 25, characterized in that R8 is R4 is H.

27. The use according to claim 1, characterized in that The triterpenoid compound of formula (I) is any of the following compounds:

28. Use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial pharmaceutical composition, wherein: The triterpenoid compound of formula (I) is as defined in any one of claims 1 to 27; the antibacterial pharmaceutical composition comprises: the triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

29. Use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for preventing and treating bacterial infection, wherein: The triterpenoid compound of formula (I) is as defined in any one of claims 1 to 27.

30. The use according to claim 29, characterized in that The bacterial infection includes drug-resistant bacterial infection diseases, and the drug-resistant bacterial infection diseases include diseases caused by infection with at least one of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and linezolid-resistant enterococci.

31. Use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of an antibacterial product, wherein: The triterpenoid compound of formula (I) is as defined in any one of claims 1 to 27.

32. The use according to claim 31, wherein: The antibacterial product includes at least one of medicines, medical devices, daily necessities, cosmetics and packaging products, and the daily necessities include one or more of cleaning products, sanitary care products, bedding, kitchen utensils, dining utensils and toys.

33. Use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof as an antibacterial agent, wherein: The triterpenoid compound of formula (I) is as defined in any one of claims 1 to 27; the application is for non-diagnostic and therapeutic purposes.

34. Use of a triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof as an inhibitor of FtsZ protein, wherein: The triterpenoid compound of formula (I) is as defined in any one of claims 1 to 27; the application is for non-diagnostic and therapeutic purposes.

35. The use according to any one of claims 1 to 34, characterized in that The triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof has a killing effect on any one, any two or all of methicillin-gold-resistant Staphylococcus aureus, vancomycin-resistant enterococci and linezolid-resistant enterococci.

36. The use according to claim 35, characterized in that The triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof also has a killing effect on one, multiple or all of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, alpha-hemolytic Streptococcus, beta-hemolytic Streptococcus, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Helicobacter pylori and Mycobacterium abscessus.

37. The use according to any one of claims 1 to 34, characterized in that The triterpenoid compound of formula (I) or a pharmaceutically acceptable salt thereof is used in any suitable form of any of the following groups: Preparations shown in Group A: tablets, capsules, granules, pills, ointments, solutions, suspensions, emulsions and creams; Preparations shown in Group B: oral solution, lozenge, injection, suppository, spray, drop, patch and tube feeding preparations; The form shown in group C: surface coating of a solid product and dopant in a solid product, wherein the solid product at least includes a plastic product.

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