Cystamine derivative and application thereof in preparation of medicine with anti-inflammatory effect

Abstract

The invention relates to a cystamine derivative and application thereof in preparation of a medicine with an anti-inflammatory effect. According to the application of the cystamine derivative or the salt of the cystamine derivative in preparation of the medicine with the anti-inflammatory effect, the cystamine derivative has the structural characteristics shown in a formula (1), a formula (2) or a formula (3). The research finds that the cystamine derivative or the salt thereof with the structural general formula can play a better anti-inflammatory effect, can be used for preventing and treating or improving inflammatory diseases, and has the characteristics of low liver and kidney toxicity, high efficiency and safety. # imgabs0 #

Description

Technical Field

[0001] The present application relates to the technical field of pharmaceutical compounds, and in particular to a cystamine derivative and its application in the preparation of a drug with anti-inflammatory effect. Background Art

[0002] Inflammatory response is a common physiological or pathological process in clinical practice. It is a complex defense reaction of the biological body to foreign pathogens (such as bacteria, viruses, antigens and nuclear antibodies, etc.) or self-tissue damage, and can occur in tissues and organs in various parts of the body. The body eliminates inflammatory factors through inflammatory response, which is a process of damage and anti-damage. Many common diseases, such as pneumonia and hepatitis caused by viral infection, autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis and inflammatory bowel disease, as well as atherosclerosis and trauma repair, all fall into the category of inflammation.

[0003] Anti-inflammatory drugs are the second largest category of drugs in clinical practice, second only to anti-infective drugs. Drugs that have the activity of eliminating inflammation are collectively referred to as anti-inflammatory drugs, which can block the production or release of inflammatory mediators and inhibit inflammatory responses. Current anti-inflammatory drugs mainly include non-steroidal anti-inflammatory drugs, steroidal anti-inflammatory drugs and biological agents. However, non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs have problems such as poor selectivity and obvious side effects (such as reducing the immune repair capacity of tissues and organs and damaging the body), and their clinical application is greatly limited; biological agents usually only target specific inflammatory factors and it is difficult to alleviate inflammatory responses caused by other inflammatory factors. Summary of the invention

[0004] Based on this, the present application provides the use of cystamine derivatives in the preparation of drugs with anti-inflammatory effects, and a class of cystamine derivatives that can exert higher anti-inflammatory effects.

[0005] In a first aspect of the present application, a cystamine derivative or a salt thereof is provided for use in preparing a drug having an anti-inflammatory effect, wherein the cystamine derivative has a structural feature as shown in the following formula (1), formula (2) or formula (3):

[0006]

[0007] Among them, L 11 , L 12 are each independently an ester group or an amide group;

[0008] R 11 , R 12 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 11 , R 12Each is independently substituted or unsubstituted by at least one S1, wherein S1 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino;

[0009] R 13 , R 14 Each independently represents H, -ester-C1-C10 alkyl or -amide-C1-C10 alkyl;

[0010]

[0011] Among them, L 21 is an ester group or an amide group;

[0012] R 21 is -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 21 is substituted or unsubstituted with at least one S2, wherein S2 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino;

[0013] R 22 It is amino group;

[0014] R 23 is H, -ester-C1-C10 alkyl or -amide-C1-C10 alkyl;

[0015]

[0016] Among them, L 31 is an ester group or an amide group;

[0017] R 31 is -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 21 It is substituted or unsubstituted with at least one S3, wherein S3 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino.

[0018] In one embodiment, R 11 , R 12 , R21 , R 31 The heteroaryl groups in are each independently indolyl or pyridyl.

[0019] In one embodiment, R 11 , R 12 , R 21 , R 31 The aryl groups in are each independently phenyl or naphthyl.

[0020] In one embodiment, R 11 , R 12 , R 21 , R 31 Each is independently -C1~C10 alkyl-C3~C15 heteroaryl, C3~C15 heteroaryl, -C1~C10 alkyl-C6~C15 aryl or C6~C15 aryl.

[0021] In one embodiment, S1, S2, and S3 independently include one or more of H, C1~C10 alkoxy, halogen, -ester-C1~C10 alkyl, -amide-C1~C10 alkyl, -ester-C1~C10 alkoxy, -amide-C1~C10 alkoxy and amino.

[0022] In one embodiment, the cystamine derivative has one of the structures shown in CS1 to CS35 below:

[0023]

[0024]

[0025]

[0026]

[0027] In one embodiment, the anti-inflammatory effect refers to preventing, treating or improving inflammatory diseases. Optionally, the inflammatory diseases include one or more of chronic colitis, psoriasis, atopic dermatitis and septic shock.

[0028] In one embodiment, the anti-inflammatory effect includes one or more of the following features:

[0029] (1) Inhibit the expression of cellular inflammatory genes;

[0030] (2) Inhibit the secretion of cellular inflammatory factors;

[0031] (3) inhibit the proliferation of keratinocytes;

[0032] (4) Reduce liver and kidney toxicity.

[0033] In a second aspect of the present application, a cystamine derivative is provided, having the structural features shown in the following formula (4) or formula (5):

[0034]

[0035] Among them, L 41 , L 42 are each independently an ester group or an amide group;

[0036] R 41 , R 42 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 41 , R 42 is unsubstituted, or R 41 , R 42 is substituted by halogen, and R 41 , R 42 Each is independently -C2~C10 alkyl-C3~C15 heteroaryl;

[0037]

[0038] Among them, L 51 is an ester group or an amide group;

[0039] R 51 is C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 51 is substituted or unsubstituted with at least one S5, wherein S5 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino;

[0040] R 52 It is amino.

[0041] In one embodiment, the cystamine derivative has one of the following structures:

[0042]

[0043] The present application has found that cystamine derivatives or salts thereof having the general structural formula shown above can exert good anti-inflammatory effects, can be used to prevent or improve inflammatory diseases, have low liver and kidney toxicity, and are highly effective and safe.

[0044] Furthermore, the present application has the following advantages:

[0045] (1) Compared with the first-line drug tapinarof, cystamine derivatives have stronger therapeutic effects on psoriasis.

[0046] (2) Compared with the first-line drug crisaborole, CS1 has a stronger therapeutic effect on atopic dermatitis.

[0047] (3) Compared with first-line anti-inflammatory drugs, CS1 has a stronger anti-inflammatory effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 The graph shows the inhibition of the expression of inflammatory factor TNF-α in BV2 cells by compounds CS1 to CS35. Ctrl represents the normal cell control group that was not stimulated with LPS.

[0049] Figure 2 The graph shows the inhibition of the expression of inflammatory factor IL6 in BV2 cells by compounds CS1 to CS35. Ctrl represents the normal cell control group that was not stimulated with LPS.

[0050] Figure 3 The graph shows the inhibition of the expression of inflammatory factor IL1-β in BV2 cells by compounds CS1 to CS35. Ctrl represents the normal cell control group that was not stimulated with LPS.

[0051] Figure 4 This is a graph showing the inhibitory effect of compound CS1 on the expression of inflammatory factors (IL1β, IL6, TNFα, IL18, MCP-1, IL23a, IFNβ, CXCL10, INOS, COX2) in RAW264.7 cells. CTRL represents the normal cell control group that was not stimulated with LPS.

[0052] Figure 5 The graph shows the results of the inhibition of the secretion of inflammatory factors (IL1β, IL6, TNFα) by compound CS1 in RAW264.7 cells. CTRL represents the normal cell control group that was not stimulated with LPS.

[0053] Figure 6 The graph shows the results of the inhibition of keratinocyte proliferation by compound CS1. CTRL represents the normal cell control group that was not stimulated with LPS.

[0054] Figure 7 The figure is a result diagram of the therapeutic effect of compound CS1 on psoriasis, CTRL represents the normal mouse control group that was not stimulated by IMQ application, and Vehicle represents the blank group that was stimulated by IMQ application and then only PEG solvent was applied to the back.

[0055] Figure 8This figure shows the research results that compound CS1 improves the survival rate of mice with septic shock.

[0056] Fig. 9 This is a graph showing the results of a study on the improving effect of compound CS1 on chronic colitis. Ctrl represents a normal mouse control group that was not stimulated with DSS.

[0057] Fig.10 This is a graph showing the results of a study on the improvement effect of compound CS1 on atopic dermatitis. Ctrl represents a normal mouse control group that was not stimulated by MC903 application, and Vehicle represents a blank group that was stimulated by MC903 application and then only PEG solvent was applied to the back.

[0058] Fig.11 The graph shows the results of a study on the hepato-renal toxicity of compound CS1 on psoriasis model mice. Ctrl represents a normal mouse control group that was not stimulated with IMQ, and Vehicle represents a blank group that was stimulated with IMQ and then only had PEG solvent applied to the back.

[0059] Fig.12 The graph shows the results of a study on the hepato-renal toxicity of compound CS1 on atopic dermatitis model mice. Ctrl represents the normal mouse control group that was not stimulated by MC903 application, and Vehicle represents the blank group that was stimulated by MC903 application and then only PEG solvent was applied to the back.

[0060] Fig.13 This is a comparison of the anti-inflammatory effects of compound CS1 and traditional anti-inflammatory compounds. Ctrl represents the normal cell control group without LPS stimulation. DETAILED DESCRIPTION

[0061] The following is a further detailed description of the cystamine derivatives of the present application and their use in the preparation of medicines with anti-inflammatory effects in conjunction with specific examples. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thoroughly understood.

[0062] 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 specific embodiments and are not intended to limit this application.

[0063] In this application, "the first aspect", "the second aspect", etc. are only used 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, "the first", "the second", 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.

[0064] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0065] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0066] The percentage contents involved in this application, unless otherwise specified, refer to mass percentage for solid-liquid mixing and solid-solid mixing, and refer to volume percentage for liquid-liquid mixing.

[0067] The percentage concentrations mentioned in this application, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0068] The temperature parameters in this application, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range of instrument control.

[0069] The room temperature in the present application generally refers to 4°C to 30°C, preferably 20±5°C.

[0070] In this application, "ester group" refers to

[0071] In this application, "amide group" refers to

[0072] In the present application, "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, for example, "C1-C10 alkyl" refers to an alkyl containing 1 to 10 carbon atoms, and each occurrence can be independently C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl or C10 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(C H3)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)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH( 2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3 and octyl (-(CH2)7CH3).

[0073] In the present application, "alkoxy" refers to a group having a structure of -O-alkyl, i.e., an alkyl group as defined above is connected to an adjacent group via an oxygen atom. A phrase containing the term, for example, "C1-C10 alkoxy" means that the alkyl portion contains 1 to 10 carbon atoms, and each occurrence may be independently C1 alkoxy, C2 alkoxy, C3 alkoxy, C4 alkoxy, C5 alkoxy, C6 alkoxy, C7 alkoxy, C8 alkoxy, C9 alkoxy, C10 alkoxy. 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).

[0074] In the present application, "aryl" refers to an aromatic hydrocarbon group derived from an aromatic ring compound by removing a hydrogen atom, which can be a monocyclic aromatic group, a condensed aromatic group, or a polycyclic aromatic group. For polycyclic rings, at least one is an aromatic ring system. For example, "C6-C15 aromatic group" refers to an aromatic group containing 6 to 15 carbon atoms, and each time it appears, it can be independently C6 aromatic group, C7 aromatic group, C8 aromatic group, C9 aromatic group, C10 aromatic group, C11 aromatic group, C12 aromatic group, C13 aromatic group, C14 aromatic group, C15 aromatic group. Suitable examples include, but are not limited to, benzene, biphenyl, naphthalene, anthracene, phenanthrene, diphenylene, triphenylene and their derivatives.

[0075] In the present application, "heteroaryl" means that at least one carbon atom on the basis of aryl is replaced by a non-carbon atom, and the non-carbon atom can be an N atom, an O atom, an S atom, etc. For example, "C3-C15 heteroaryl" means a heteroaryl containing 3 to 15 carbon atoms, and each occurrence can be independently C3 heteroaryl, C4 heteroaryl, C5 heteroaryl, C6 heteroaryl, C7 heteroaryl, C8 heteroaryl, C9 heteroaryl, C10 heteroaryl, C11 heteroaryl, C12 heteroaryl, C13 heteroaryl, C14 heteroaryl, C15 heteroaryl. Suitable examples include, but are not limited to, furanyl, benzofuranyl, thienyl, benzothienyl, pyrrolyl, pyrazolyl, triazolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, tetrazolyl, indolyl, carbazolyl, pyrroloimidazolyl, pyrrolopyrrolyl, thienopyrrolyl, thienothiphenyl, furopyrrolyl, furofuranyl, thienofuranyl, benzisoxazolyl, benzisothiazolyl, benzimidazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, o-naphthyl, quinoxalinyl, phenanthridinyl, primidinyl, quinazolinyl, and quinazolinonyl.

[0076] In the present application, "halogen" refers to F, Cl, Br or I.

[0077] As used herein, "amino" refers to -NH2.

[0078] In a first aspect of the present application, a cystamine derivative or a salt thereof is provided for use in preparing a drug having an anti-inflammatory effect, wherein the cystamine derivative has a structural feature as shown in the following formula (1), formula (2) or formula (3):

[0079]

[0080] Among them, L 11 , L 12 are each independently an ester group or an amide group;

[0081] R 11 , R 12 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 11 , R 12 Each is independently substituted or unsubstituted by at least one S1, wherein S1 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino;

[0082] R 13 , R 14 Each independently represents H, -ester-C1-C10 alkyl or -amide-C1-C10 alkyl;

[0083]

[0084] Among them, L 21 is an ester group or an amide group;

[0085] R 21 is -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 21 is substituted or unsubstituted with at least one S2, wherein S2 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino;

[0086] R 22 It is amino group;

[0087] R 23 is H, -ester-C1-C10 alkyl or -amide-C1-C10 alkyl;

[0088]

[0089] Among them, L 31 is an ester group or an amide group;

[0090] R 31 is -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 21 It is substituted or unsubstituted with at least one S3, wherein S3 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino.

[0091] In some of these examples, R 11 , R 12 , R 21 , R 31 The heteroaryl groups in are each independently indolyl or pyridyl.

[0092] In some of these examples, R 11 , R 12 , R 21 , R 31 The aryl groups in are each independently phenyl or naphthyl.

[0093] In some of these examples, R 11 , R 12 , R 21 , R 31 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl. 11 , R 12 , R 21 , R 31 Each is independently -C1~C10 alkyl-C3~C15 heteroaryl, -C1~C10 alkyl-C6~C15 aryl or C6~C15 aryl.

[0094] In some of the examples, S1, S2, and S3 each independently include one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy, and amino.

[0095] In some of these examples, L 11 , L 12 , L 21 , L 31are each independently an amide group.

[0096] In some of the examples, the alkyl group in -C1-C10 alkyl-C3-C15 heteroaryl and -C1-C10 alkyl-C6-C15 aryl is a C1-C5 alkyl group, further a C1-C3 alkyl group, and further a C2 alkyl group.

[0097] In some examples, the cystamine derivative satisfies one of the following conditions:

[0098] (1) When S1 includes a C1-C10 alkoxy group, R 11 , R 12 is not -C2 alkyl-C3-C15 heteroaryl;

[0099] (2) When S1 includes Br, L 11 , L 12 Not an ester group.

[0100] Without limitation, the cystamine derivative has one of the structures shown in the following CS1 to CS35:

[0101]

[0102]

[0103]

[0104]

[0105] In some of these examples, the anti-inflammatory effect refers to preventing, treating or improving inflammatory diseases. Optionally, the inflammatory diseases include one or more of chronic colitis, psoriasis, atopic dermatitis and septic shock.

[0106] In some examples, the anti-inflammatory effect includes one or more of the following characteristics:

[0107] (1) Inhibit the expression of cellular inflammatory genes;

[0108] (2) Inhibit the secretion of cellular inflammatory factors;

[0109] (3) inhibit the proliferation of keratinocytes;

[0110] (4) Reduce liver and kidney toxicity.

[0111] Some other examples of the present application also provide a cystamine derivative having the structural features shown in the following formula (4) or formula (5):

[0112]

[0113] Among them, L41 , L 42 are each independently an ester group or an amide group;

[0114] R 41 , R 42 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 41 , R 42 is unsubstituted, or R 41 , R 42 is substituted by halogen, and R 41 , R 42 Each is independently -C2~C10 alkyl-C3~C15 heteroaryl;

[0115]

[0116] Among them, L 51 is an ester group or an amide group;

[0117] R 51 is C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 51 is substituted or unsubstituted with at least one S5, wherein S5 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino;

[0118] R 52 It is amino.

[0119] In some of these examples, R 41 , R 51 The heteroaryl groups in are each independently indolyl or pyridyl.

[0120] In some of these examples, R 41 , R 51 The aryl groups in are each independently phenyl or naphthyl.

[0121] In some of these examples, R 41 , R 51 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl. 41 , R 51Each is independently -C1~C10 alkyl-C3~C15 heteroaryl, -C1~C10 alkyl-C6~C15 aryl or C6~C15 aryl.

[0122] In some of these examples, S5 independently includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino.

[0123] In some of these examples, L 41 , L 42 , L 51 Each is independently an ester group.

[0124] In some of the examples, the alkyl group in -C1-C10 alkyl-C3-C15 heteroaryl and -C1-C10 alkyl-C6-C15 aryl is a C1-C5 alkyl group, further a C1-C3 alkyl group, and further a C2 alkyl group.

[0125] Without limitation, the cystamine derivative has one of the following structures:

[0126]

[0127]

[0128] For experimental parameters not specified in the following specific embodiments, reference is made to the instructions given in the present application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by manufacturers.

[0129] The raw materials and reagents involved in the following specific examples can be obtained from commercial sources, or can be prepared by those skilled in the art according to known methods.

[0130] Example 1

[0131] This example provides compounds CS1 to CS35, the structures of which are shown in Table 1 below.

[0132] Table 1

[0133]

[0134]

[0135]

[0136]

[0137] Among them, compounds CS2, CS5, CS6, CS8, CS11, CS12, CS14, CS15, CS16, CS17, CS18, CS19, CS20, CS22, CS23, CS24, CS25, CS26, CS27, CS28, CS29, CS30, CS31, CS32, CS33, CS34 and CS35 are existing compounds and can be synthesized by referring to existing methods or the preparation methods of the following compounds CS1, CS3, CS4, CS7, CS9, CS10, CS13, CS21.

[0138] Compounds CS1, CS3, CS4, CS7, CS9, CS10, CS13 and CS21 are homemade compounds, and their preparation methods and structural identification data are as follows:

[0139] Synthesis of CS-1:

[0140]

[0141] 3-Indolepropionic acid (630 mg, 3.33 mM, 2.5 eq) was dissolved in DCM: ACN (6: 3), and then EDCI (1.02 g, 5.32 mM, 4 eq) and NHS (612 mg, 5.32 mM, 4 eq) were added, and the mixture was reacted at room temperature for 2 h. Cystamine dihydrochloride (300 mg, 1.33 mM, 1 eq) and triethylamine (1.6 mL, 11.9 mM, 9 eq) were dissolved in 10 mL ACN and added dropwise to the reaction system, and the mixture was reacted at room temperature overnight. After the reaction was complete as monitored by TLC, the reaction solution was dried by spin drying, redissolved in DCM, extracted with water for 3 times, the DCM layers were combined, washed with saturated brine, the DCM layer was dried by spin drying with silica gel, and passed through a fast silica gel column (DCM: MeOH / 150: 1), the target spot was collected, and a white solid (321 mg, yield: 49%) was obtained by spin drying. After recrystallization, 130 mg of pure product was finally obtained. 1 HNMR(400MHz,DMSO)δ10.7(s,2H),8.05(t,J=5.52Hz,2H),7.51(d,J=7.8Hz,2H),7.31(d,J=8.04Hz,2H),7.08-7.03(m,4H) ,6.95(t,J=7.08Hz,2H),3.34(m,4H),2.91(t,J=7.44Hz,4H),2.74(t,J=6.92Hz,4H),2.44(t,J=8.12Hz,4H),ESI-MS:calcd for C 26 H 30 N4O2S2,[M+H] + m / z 517.1702, found, 517.1722, purity 99%.

[0142] Synthesis of CS-3 (Cystamine Dibutyrate):

[0143]

[0144] Butyric acid (366 μL, 4 mM, 3 eq) was dissolved in 6 mL DCM, and then EDCI (1.02 g, 5.32 mM, 4 eq) and NHS (612 mg, 5.32 mM, 4 eq) were added, and the reaction was carried out at room temperature for 2 h. Cystamine dihydrochloride (300 mg, 1.33 mM, 1 eq) and triethylamine (1.6 mL, 11.9 mM, 9 eq) were dissolved in 10 mL ACN and added dropwise to the reaction system, and the reaction was carried out at room temperature overnight. After TLC monitoring of the reaction was complete, the reaction solution was spin-dried, redissolved in DCM, extracted with water 3 times, the DCM layers were combined, washed with saturated brine, the DCM layer was spin-dried with silica gel, and passed through a fast silica gel column (DCM: MeOH / 100: 1), the target point was collected, and spin-dried to obtain a white solid (158 mg, yield: 41%). 1 HNMR (400MHz, CDCl3) δ6.35 (s, 2H), 3.57 (dd, J = 12.56, 6.32Hz, 4H), 2.83 (t, J = 6.4Hz, 4H),2.20(t,J=7.36Hz,4H),1.72-1.63(m,4H),0.95(t,J=7.36Hz,6H),ESI-MS:calcd forC 12 H 24 N2O2S2,[M+Na] + m / z 315.1171, found, 315.1195, purity 97%.

[0145] Synthesis of CS4 (Cystamine dinicotinate):

[0146]

[0147] Nicotinic acid (410 mg, 3.33 mM, 2.5 eq) was dissolved in 20 mL DCM, and HOBt (540 mg, 3.99 mM, 3 eq) and EDCl (765 mg, 3.99 mM, 3 eq) were added. The mixture was protected by N2 and stirred at room temperature for 20 min. Cystamine hydrochloride (300 mg, 1.33 mM, 1 eq) and Et3N (924 μL, 6.65 mM, 5 eq) were added and the reaction was allowed to proceed overnight. The reaction was basically complete under TLC monitoring. Saturated NaHCO3 was added and the mixture was extracted with DCM three times. The DCM layers were combined and washed with saturated brine. The DCM layer was dried with silica gel and passed through a fast silica gel column (DCM: MeOH / 25:1). The target spot was collected and dried to obtain 388 mg of the product (yield 80%). The product was then dissolved in DCM / MeOH (5 / 5 mL), and about 10 mL of n-hexane was added for recrystallization. 295 mg of the product was collected by filtration. 1 HNMR(400MHz,DMSO)δ9.0(s,2H),8.86(s,2H),8.70(s,2H),8.17(d,J=7.52Hz,2H), 7.51(d,J=4.4Hz,2H),3.59(d,J=5.52Hz,4H),2.95(t,J=6.08Hz,4H),ESI-MS:calcd for C 16 H 18 N4O2S2, [M+Na]+cald 385.0763, found 385.0777, purity 99%.

[0148] Synthesis of CS7 (cystamine monobutyrate):

[0149]

[0150] Butyric acid (100 μL, 1.09 mM, 1 eq), EDCI (1.045 g, 5.45 mM, 5 eq), and cystamine dihydrochloride (1.23 g, 5.45 mM, 5 eq) were dissolved in 3 mL of H2O, the pH was adjusted to 6.0 with 0.1 M NaOH, and the reaction was carried out at room temperature for 4 h. The reaction was monitored by HPLC, and 5 peaks were collected for mass spectrometry identification, among which the 5th peak was the target peak, which was separated and purified by HPLC and freeze-dried to obtain an oily product. 1HNMR (400MHz, DMSO) δ8.0(t,J=4.92Hz,1H),7.92(s,2H),3.34(dd,J=12.92,6.48Hz,2H),3.10(d,J=5.32Hz,2H),2.91(t ,J=7.2Hz,2H),2.79(t,J=6.92Hz,2H),2.04(t,J=7.28Hz,2H),1.55-1.46(m,2H),0.85(t,J=7.36Hz,3H),ESI-MS:calcd for C8H 18 N2OS2,[M+H] + 223.3, found 223.2, purity 97%.

[0151] Synthesis of CS9 (diindolebutyric acid cystamine):

[0152]

[0153] Indolebutyric acid (338 mg, 1.665 mmoL, 2.5 eq), EDCI (383 mg, 2 mmoL, 3 eq), and HOBt (230 mg, 2 mmoL, 3 eq) were dissolved in 15 mL DCM and reacted with stirring at room temperature for 10 min. Cystamine dihydrochloride (150 mg, 0.66 mmoL, 1 eq) and Et3N (463 μL, 3.33 mmoL, 5 eq) were dissolved in 5 mL DCM and added to the reaction system. The reaction was allowed to proceed overnight. The basic reaction was monitored by TLC to be complete. The reaction was stopped. The reaction solution was washed with saturated NaHCO3, ultrapure water, and saturated NaCl, and then silica gel was added and spin-dried. The mixture was purified by silica gel column (DCM: MeOH / 75:1) to obtain diindolebutyric acid cystamine (220 mg, yield: 64%). 1 HNMR (400MHz, DMSO) δ10.74(s,2H),7.98(t,J=5.52Hz,2H),7.48(d,J=7.84Hz,2H),7.31(d,J=8.04Hz,2H),7.08-7.02(m,4H),6.94(t,J= 7.76Hz,2H),3.35-3.30(m,4H),2.77(t,J=6.84Hz,4H),2.65(t,J=7.44Hz,4H),2.13(t,J=7.36Hz,4H),1.89-1.82(m,4H),ESI-MS:calcd forC 28 H 34 N4O2S2,[M+Na] + 545.7, found 545.25, purity 99%.

[0154] Synthesis of CS10 (diindolecarboxylic acid cystamine):

[0155]

[0156] Indolecarboxylic acid (268 mg, 1.665 mmoL, 2.5 eq), EDCI (383 mg, 2 mmoL, 3 eq), and HOBt (230 mg, 2 mmoL, 3 eq) were dissolved in 15 mL DCM and reacted with stirring at room temperature for 10 min. Cystamine dihydrochloride (150 mg, 0.66 mmoL, 1 eq) and Et3N (463 μL, 3.33 mmoL, 5 eq) were dissolved in 5 mL DCM and added to the reaction system. The reaction was allowed to proceed overnight. The basic reaction was monitored by TLC to be complete. The reaction was stopped. The reaction solution was washed with saturated NaHCO3, ultrapure water, and saturated NaCl, and then silica gel was added and spin-dried. The mixture was purified by silica gel column (DCM: MeOH / 50:1) to obtain diindolecarboxylic acid cystamine (106 mg, yield: 37%). 1 HNMR (400MHz, DMSO) δ11.53(s,2H),8.14-8.10(m,4H),8.01(d,J=2.92Hz,2H),7.41(d,J=7.92H z,2H),7.15-7.06(m,4H),3.57(dd,J=13.48,6.24Hz,4H),2.95(t,J=2.92Hz,4H),ESI-MS:calcd forC 22 H 22 N4O2S2,[M+H] + 439.56, found 439.15, purity 99%.

[0157] Synthesis of CS13 (diindoleacetic acid cystamine):

[0158]

[0159] Indoleacetic acid (194 mg, 1.11 mmoL, 2.5 eq), EDCI (255 mg, 1.332 mmoL, 3 eq), and HOBt (153 mg, 1.332 mmoL, 3 eq) were dissolved in 10 mL DCM and reacted at room temperature with stirring for 10 min. Cystamine dihydrochloride (100 mg, 0.44 mmoL, 1 eq) and Et3N (309 μL, 2.22 mmoL, 5 eq) were dissolved in 5 mL DCM and added to the reaction system. The reaction was allowed to proceed overnight. The basic reaction was monitored by TLC to be complete. The reaction was stopped. The reaction solution was washed with saturated NaHCO3, ultrapure water, and saturated NaCl, and then silica gel was added and spin-dried. The mixture was purified by silica gel column (DCM: MeOH / 30:1) to obtain diindoleacetic acid cystamine (113 mg, yield: 55%).1 HNMR (400MHz, DMSO) δ10.85(s,2H),8.05(t,J=5.56Hz,2H),7.53(d,J=7.92Hz,2H),7.32(d,J=8.08Hz,2H),7.17(s ,2H),7.07-7.03(m,2H),6.97-6.93(m,2H),3.50(s,4H),3.34-3.29(m,4H),2.74(t,J=6.96Hz,4H),ESI-MS:calcd for C 24 H 26 N4O2S2,[M+Na] + 489.62, found 489.15, purity 98%.

[0160] Synthesis of CS21 (5-bromo-indolepropionic acid cystamine):

[0161]

[0162] 5-Bromo-indolepropionic acid (298 mg, 1.11 mmoL, 2.5 eq), EDCI (255 mg, 1.32 mmoL, 3 eq), and HOBt (153 mg, 1.32 mmoL, 3 eq) were dissolved in 10 mL DCM and reacted at room temperature with stirring for 10 min. Cystamine dihydrochloride (100 mg, 0.44 mmoL, 1 eq) and Et3N (309 μL, 2.2 mmoL, 5 eq) were dissolved in 5 mL DCM and added to the reaction system. The reaction was allowed to proceed overnight. The basic reaction was monitored by TLC to be complete. The reaction was stopped. The reaction solution was washed with saturated NaHCO3, ultrapure water, and saturated NaCl, and then silica gel was added and spin-dried. The mixture was purified by silica gel column (DCM: MeOH / 40:1) to obtain 5-bromo-indolepropionic acid cystamine (189 mg, yield: 66%). 1 HNMR (400MHz, DMSO) δ10.96 (s, 2H), 8.03 (t, J = 5.52Hz, 2H), 7.69 (d, J = 1.76Hz, 2H), 7.29 (d, J = 8.6Hz, 2H), 7.16-7.14 (m,4H),3.32(t,J=7.24Hz,4H),2.89(t,J=7.44Hz,4H),2.73(t,J=6.96Hz,4H),2.41(t,J=7.6Hz,4H),ESI-MS:calcd for C 26 H 28 Br2N4O2S2,[M+Na] + 672.9913, found 672.9903, purity 99%.

[0163] Example 2

[0164] This example provides a study on the anti-inflammatory activity of compounds CS1 to CS35.

[0165] BV2 cells were used to study the inhibitory effect of compounds on the expression of inflammatory factors (TNF-α, IL6, IL1-β) at the cellular level. BV2 cells were seeded in 6-well plates, 5×10 5 / mL, 1μg / mL LPS was added to induce inflammatory response in BV2 cells, and 10μM of the compound was added. Figures 1 to 3 As shown in Table 2, it can be seen that compounds CS1 to CS35 have good anti-inflammatory activity.

[0166] Table 2

[0167]

[0168]

[0169] Example 3

[0170] This example provides a study on the inhibition of cellular inflammatory gene expression by CS1.

[0171] RAW264.7 cells were used to study the inhibitory effect of CS1 on the expression of inflammatory factors (IL1β, IL6, TNFα, IL18, MCP-1, IL23a, IFNβ, CXCL10, INOS, COX2) at the cellular level. RAW264.7 cells were seeded in 12-well plates at 4×10 5 / mL, 1μg / mL LPS was added to induce inflammatory response of cells. Figure 4 As shown, setting a CS1 concentration gradient (5 μM, 10 μM, 25 μM) can significantly inhibit the expression of LPS-induced inflammatory genes in a concentration-dependent manner, and the effect is significantly better than that of tapinarof (abbreviated as tapi) at the same concentration (10 μM).

[0172] Example 4

[0173] This example provides a study on the inhibition of secretion of inflammatory factors by CS1.

[0174] RAW264.7 cells were used to study the inhibitory effect of CS1 on the secretion of inflammatory factors (IL1β, IL6, TNFα) and inflammatory mediator nitric oxide (NO) at the cellular level. RAW264.7 cells were seeded in 6-well plates at 4×10 5 / mL, 1μg / mL LPS was added to induce inflammatory response of cells. Figure 5As shown, setting a CS1 concentration gradient (5 μM, 10 μM, 25 μM) can significantly inhibit the secretion of LPS-induced inflammatory factors and NO in a concentration-dependent manner, and the effect is significantly better than that of tapinarof at the same concentration (10 μM).

[0175] Example 5

[0176] This example provides a study on the inhibition of HACAT cell proliferation by CS1.

[0177] Keratinocyte HACAT was used to study the inhibitory effect of CS1 on the proliferation and migration of keratinocytes, a key cell in the pathogenesis of psoriasis. HACAT cells were seeded in 24-well plates, 2×10 5 When the cells reached 80-90% confluence, a scratch was made in the center of the well with the tip of a gun. After washing the cells, the medium was replaced with new one and different gradient concentrations of CS1 (10 μM, 50 μM) were added. The cell proliferation and metastasis were observed at different time points. Figure 6 As shown, CS1 can significantly inhibit the proliferation of HACAT cells in a concentration gradient-dependent manner.

[0178] Example 6

[0179] This example provides a study on the therapeutic effect of CS1 on psoriasis.

[0180] IMQ (imiquimod) ointment was used to induce psoriasis on the back skin of mice. After 7 days of treatment with 62.5 mg / mouse / day, the back was treated with different concentrations of CS1 for 3 days. Figure 7 As shown in the figure, the CS1 group significantly improved the weight loss (B), dandruff and redness (C) caused by IMQ, and the psoriasis disease score PASI was also significantly reduced. Pathological tissue sections showed that the epidermis of the back skin of mice in the IMQ group was thickened, while CS1 treatment could significantly reduce its thickness and reduce the infiltration of immune cells in the dermis (D).

[0181] Example 7

[0182] This example provides research showing that CS1 significantly improves the survival rate of mice with septic shock.

[0183] A lethal dose of LPS (30 mg / kg) was intraperitoneally injected into C57BL / 6J mice to establish an experimental model of septic shock. The purpose was to test whether CS1 could effectively prolong the survival time of mice with septic shock, and then evaluate the protective effect of CS1 on the body. The body temperature and weight of the mice were recorded before the experiment (5 mice per group). Then, 20 mg / kg CS1 was gavaged and 30 mg / kg LPS was intraperitoneally injected. The experimental mice were observed for 4 consecutive days. The results are as follows: Figure 8As shown in the figure. The mortality rate of mice in the non-medication group was as high as 80% within 4 days, while there was no death in mice taking 20mg / kg CS1, and most of the mice in the medication group began to recover in body temperature after 24 hours, and their body weight also recovered after 72 hours. This shows that CS1 can significantly improve the survival rate of the LPS-induced acute mouse shock model, and CS1 has a certain protective effect on the body.

[0184] Example 8

[0185] This example provides a study on the improving effect of CS1 on chronic colitis.

[0186] Balb / c mice were given sterile water containing 4% DSS to establish a chronic colitis model, so as to preliminarily explore whether CS1 has anti-inflammatory effects in vivo and maintains intestinal homeostasis. The initial weight of the mice was recorded before the experiment, and then the mice were required to drink sterile water containing 4% DSS for 8 consecutive days (drinking normal sterile water on the 9th to 11th day). At the same time, the low-dose group mice were gavaged with 10 mg / kg CS1 every day, and the high-dose group mice were gavaged with 50 mg / kg CS1. CS1 was gavaged for 11 consecutive days, and the weight of the mice was recorded every day. The results are as follows: Fig. 9 As shown, CS1 can effectively slow down the rate of weight loss caused by colitis in mice, and the colon length was measured, and it was found that the colon length of mice taking CS1 was longer than that of mice in the DSS group, which further indicates that CS1 has an improving effect on chronic colitis.

[0187] Example 9

[0188] This example provides a study on the therapeutic effect of CS1 on atopic dermatitis.

[0189] Vitamin D analogue MC903 was used to induce atopic dermatitis on the back of mice. 45 μM MC903 was applied to the area of ​​about 2×3 cm on the back of balb / c mice. 100 μL was applied daily. At the same time, 25 μL was applied to each ear. The treatment cycle was: 5 days of treatment, 2 days of interruption, 5 days of treatment, 2 days of interruption, and 2 days of treatment ( Fig.10 ), CS1 was applied daily starting from the 10th day, and the disease development was observed after one week of administration. Fig.10 As shown in the figure, CS1 treatment significantly improved the redness, swelling and desquamation of the back of mice caused by MC903 (A), and the atopic dermatitis disease score SCORAD showed that the CS1 group had the highest degree of disease remission (B), and ear swelling was reduced in the CS1 group (C). Pathological tissue sections showed that the thickness of the back skin and the immune cell infiltration in the dermis of dermatitis mice were significantly reduced (DF).

[0190] Example 10

[0191] This example provides the hepato-renal toxicity of CS1.

[0192] The hepatorenal toxicity after CS1 treatment was detected in mice with psoriasis and atopic dermatitis models. After applying 0.1%, 1%, and 2% CS1 to the back of mice, blood was collected from the mice to measure the alanine aminotransferase ALT, aspartate aminotransferase AST, and blood urea nitrogen BUN in the mouse serum. The results showed that there was no significant increase in the levels of ALT, AST, and BUN in both the psoriasis mice induced by imiquimod ointment and the atopic dermatitis mice induced by MC903. In addition, in the psoriasis mice, the level of ALT was significantly reduced after 1% CS1 treatment ( Figure 11-12 ).

[0193] Embodiment 11

[0194] This example provides a comparison of the anti-inflammatory effects of CS1 and traditional anti-inflammatory compounds.

[0195] Using BV2 cells, the anti-inflammatory ability of CS1 and a variety of compounds with certain anti-inflammatory activity (N-acetylcysteine ​​(NAC), ergothioneine (EGT), melatonin (MET), water-soluble vitamin E (Trolox)) were compared at the cellular level. BV2 cells were seeded in 6-well plates, 5×10 5 / mL, 1μg / mL LPS was added to induce inflammatory response in BV2 cells. The concentration of each drug tested was 10μM, and it was added at the same time as LPS for a total of 10h. Fig.13 As shown, CS1 has a better anti-inflammatory effect than other compounds.

[0196] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments 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.

[0197] The above-described 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 patent application. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several modifications and improvements can be made, which all belong to the scope of protection of the present application. It should be understood that the technical solutions obtained by those skilled in the art 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 can be used to interpret the content of the claims.

Claims

1. Use of a cystamine derivative or a salt thereof in the preparation of a drug having an anti-inflammatory effect, wherein the cystamine derivative has a structural feature as shown in the following formula (1), formula (2) or formula (3): in, L 11 , L 12 are each independently an ester group or an amide group; R 11 , R 12 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 11 , R 12 Each is independently substituted or unsubstituted by at least one S1, wherein S1 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino; R 13 , R 14 Each independently represents H, -ester-C1-C10 alkyl or -amide-C1-C10 alkyl; Among them, L 21 is an ester group or an amide group; R 21 is -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 21 is substituted or unsubstituted with at least one S2, wherein S2 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino; R 22 It is amino group; R 23 is H, -ester-C1-C10 alkyl or -amide-C1-C10 alkyl; Among them, L 31 is an ester group or an amide group; R 31 is -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 21 It is substituted or unsubstituted with at least one S3, wherein S3 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino.

2. The use according to claim 1, characterized in that: R 11 , R 12 , R 21 , R 31 The heteroaryl groups in are each independently indolyl or pyridyl.

3. The use according to claim 1, characterized in that: R 11 , R 12 , R 21 , R 31 The aryl groups in are each independently phenyl or naphthyl.

4. The use according to claim 1, characterized in that: R 11 , R 12 , R 21 , R 31 Each is independently -C1~C10 alkyl-C3~C15 heteroaryl, C3~C15 heteroaryl, -C1~C10 alkyl-C6~C15 aryl or C6~C15 aryl.

5. The use according to claim 1, characterized in that: S1, S2, and S3 each independently include one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy, and amino.

6. The use according to claim 1, characterized in that: The cystamine derivative has one of the structures shown in the following CS1 to CS35:

7. The use according to any one of claims 1 to 6, characterized in that: The anti-inflammatory effect refers to preventing, treating or improving inflammatory diseases. Optionally, the inflammatory diseases include one or more of chronic colitis, psoriasis, atopic dermatitis and septic shock.

8. The use according to claim 7, characterized in that: The anti-inflammatory effect includes one or more of the following characteristics: (1) Inhibit the expression of cellular inflammatory genes; (2) Inhibit the secretion of cellular inflammatory factors; (3) inhibit the proliferation of keratinocytes; (4) Reduce liver and kidney toxicity.

9. A cystamine derivative, characterized in that It has the structural features shown in the following formula (4) or formula (5): Among them, L 41 , L 42 are each independently an ester group or an amide group; R 41 , R 42 Each is independently -C1-C10 alkyl-C3-C15 heteroaryl, C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 41 , R 42 is unsubstituted, or R 41 , R 42 is substituted by halogen, and R 41 , R 42 Each is independently -C2~C10 alkyl-C3~C15 heteroaryl; Among them, L 51 is an ester group or an amide group; R 51 is C1-C10 alkyl, C3-C15 heteroaryl, -C1-C10 alkyl-C6-C15 aryl or C6-C15 aryl; R 51 is substituted or unsubstituted with at least one S5, wherein S5 includes one or more of H, C1-C10 alkoxy, halogen, -ester-C1-C10 alkyl, -amide-C1-C10 alkyl, -ester-C1-C10 alkoxy, -amide-C1-C10 alkoxy and amino; R 52 It is amino.

10. The cystamine derivative according to claim 9, characterized in that Has one of the following structures:

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