Novel lipid compound and composition, and nucleic acid lipid nanoparticle formulation, and screening method therefor and use thereof

Abstract

A cationic lipid compound, a composition comprising the cationic lipid compound, and a use. A compound is as represented by general formula (I). Also provided are a cationic lipid compound comprising the compound, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof. The present application also relates to an immune cell-targeted lipid nanoparticle, and a screening method therefor and a use thereof. Specifically disclosed is a use of the compound of formula (I), or the pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in targeting immune cells, and also disclosed are a method for in vitro screening of lipid nanoparticles and a method for screening lipid nanoparticles suitable for delivering mRNA to various immune cells in vivo.

Description

A novel lipid compound and composition and nucleic acid lipid nanoparticle preparation and screening method and application thereof Technical Field

[0001] The present application belongs to the field of biomedicine technology, and specifically relates to a lipid compound and a lipid carrier containing the same, a nucleic acid lipid nanoparticle composition and a pharmaceutical preparation and a screening method and application thereof, an LNP-mRNA delivery system, mRNA and its use. Background Art

[0002] Gene therapy technology is a hot topic in modern biomedical research. Nucleic acid drugs can be used to prevent cancer, bacterial and viral infections, and treat diseases with genetic etiologies. Because nucleic acid drugs are easily degraded and difficult to enter cells, they require encapsulation with a vector for delivery to target cells. Therefore, the development of safe and efficient delivery vectors is a prerequisite for the clinical application of gene therapy.

[0003] Lipid nanoparticles (LNPs) are currently a research hotspot in the field of non-viral gene delivery. As a safe and efficient nucleic acid drug delivery vehicle, they have been shown to be able to efficiently deliver RNA to the liver. In 2018, the US FDA approved the world's first LNP-based liver-targeted siRNA drug. It is used to treat hereditary transthyretin-mediated amyloidosis. Furthermore, the two COVID-19 mRNA vaccines currently approved by the US FDA are also based on LNP development. However, LNP nucleic acid delivery systems still face several challenges, including the fact that LNPs are primarily targeted to the liver and the potential for immunogenicity.

[0004] LNPs are usually composed of four lipid compounds, namely cationic lipids, neutral lipids, steroids and PEG-lipids. Among them, the choice of cationic lipids has the greatest impact on LNPs, such as affecting the encapsulation rate of nucleic acid drugs, the delivery site and efficiency of nucleic acid drugs in the body, and cytotoxicity.

[0005] Immune cell therapies include CAR-T, CAR-NK, CAR-DC, and CAR-Macrophage. A variety of these therapies, especially CAR-T, have achieved tremendous success in the treatment of hematologic malignancies. However, single-cell immune cell therapies still have limitations in the treatment of solid tumors. This is because the tumor microenvironment is often isolated within a dense, fibrous mass, making it difficult for immune cells to infiltrate and exert their killing effects. Furthermore, the immunosuppressive microenvironment can easily lead to cell exhaustion. Traditional methods of forming CAR-immune cells in vitro and then reintroducing them into the body often suffer from low editing efficiency and long construction times. Therefore, how to form multiple CAR-immune cells in vivo, stimulate an immune response at the tumor site, and enhance the anti-tumor effect of a single CAR-immune cell remains a current challenge.

[0006] In view of this, it would be of great significance to develop a new compound that can serve as a cationic lipid.

[0007] Summary of the Invention

[0008] Problems to be solved by the invention

[0009] The first purpose of this application is to provide a series of compounds that can be used together with other lipid compounds to prepare lipid carriers to improve the delivery efficiency of nucleic acid drugs in the body. Lipid compounds with specific structures can be selected as lipid carriers according to the organs where the nucleic acid drugs need to be enriched.

[0010] The second object of the present application is to provide a lipid carrier comprising the above compound.

[0011] The third object of the present application is to provide a nucleic acid lipid nanoparticle composition comprising the above compound or the above lipid carrier.

[0012] The fourth object of the present application is to provide a pharmaceutical preparation comprising the above-mentioned compound, or the above-mentioned lipid carrier, or the above-mentioned nucleic acid lipid nanoparticle composition.

[0013] Specific technical solution of the invention

[0014] In one embodiment, the present application provides a cationic lipid compound represented by the general formula (I), or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein X, Y, Z, G1, G2, G3, G4, G5, G6, L1, L2, L3, L4 are as defined in this application or elsewhere.

[0015] In one embodiment, the present application provides a nanoparticle composition comprising a compound provided herein and a therapeutic or prophylactic agent. In one embodiment, the therapeutic or prophylactic agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof.

[0016] Additional features of the present disclosure will become apparent to those skilled in the art after considering the following detailed description of specific embodiments.

[0017] Specifically, this application adopts the following technical solutions:

[0018] 1. A compound of formula (I):

[0019] or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein:

[0020] The G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group;

[0021] The L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-;

[0022] R a and R b are each independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;

[0023] x is 0, 1, or 2;

[0024] Said G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene group;

[0025] The L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d-、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-;

[0026] R c and R d are each independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;

[0027] i is 0, 1, or 2;

[0028] Said G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkyl group or an optionally substituted C2-C24 straight chain alkenyl group;

[0029] The Z is an optionally substituted C1-C12 alkylene, an optionally substituted -R e G7R f -;

[0030] Among them, R e and R f is an optionally substituted C1-C12 alkylene group;

[0031] G7-NR g -, -(3-7 membered saturated cycloalkane)-, -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-;

[0032] R g is an optionally substituted C1-C12 alkylene group;

[0033] Said X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0034] 2. The compound according to item 1, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IA):

[0035] wherein G1, G2, G3, G4, G5, G6, L1, L2, L3, L4, X, and Y are as defined in item 1;

[0036] G8 is an optionally substituted C1-C12 alkylene group.

[0037] 3. The compound according to item 1, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IB):

[0038] Among them, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e 、R f , X and Y are as defined in item 1.

[0039] 4. The compound according to any one of items 1 to 3, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein G1 and G2 are unsubstituted C2-C4 alkylene.

[0040] 5. The compound according to any one of items 1 to 4, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein L1 and L2 are -C(=O)O-.

[0041] 6. The compound according to any one of items 1 to 5, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein G3 and G4 are a bond.

[0042] 7. The compound according to any one of items 1 to 5, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein G3 and G4 are unsubstituted C2-C4 alkylene.

[0043] 8. The compound according to any one of items 1 to 6, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein L3 and L4 are a bond.

[0044] 9. The compound according to any one of items 1-5 and 7, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that L3 and L4 are -OC(=O)O-.

[0045] 10. The compound according to any one of items 1 to 9, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that G5 and G6 are optionally substituted C4-C16 straight chain alkenyl groups.

[0046] 11. The compound according to any one of items 2 and 4 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IA-1):

[0047] Wherein, m is 1 or 3, n is 0 or 1, G5 and G6 are defined as in item 10, G8 is defined in item 2, G9 and G 10is an optionally substituted C1-C5 straight-chain alkane.

[0048] 12. The compound according to any one of items 2 and 4 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IA-2):

[0049] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in item 10.

[0050] 13. The compound according to any one of items 2 and 4 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IA-3):

[0051] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in item 10.

[0052] 14. The compound according to any one of items 2 and 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IA-4):

[0053] wherein G1, G2, G3, G4, G5, G6, L1, L2, L3, L4 and Y are as defined in item 1; and G8 is an optionally substituted C1-C12 alkylene group.

[0054] 15. The compound according to any one of items 2 and 4 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein the compound has a structure represented by formula (IA-5):

[0055] wherein m is 1 or 3, n is 0 or 1, Y, G5 and G6 are as defined in item 1; and G8 is an optionally substituted C1-C12 alkylene group.

[0056] 16. The use according to any one of items 2 and 4 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein the compound has a structure represented by formula (IA-6):

[0057] wherein m is 1 or 3, n is 0 or 1, and Y, G5 and G6 are as defined in item 1.

[0058] 17. The compound according to any one of items 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IB-1):

[0059] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in item 10.

[0060] 18. The compound according to any one of items 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IB-2):

[0061] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in item 10.

[0062] 19. The compound according to any one of items 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that the compound has a structure represented by formula (IB-3):

[0063] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in item 10.

[0064] 20. The use according to any one of items 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein the compound has a structure represented by formula (IB-4):

[0065] Among them, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e and R f As defined in item 1.

[0066] 21. The compound according to any one of items 2 and 4 to 11, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that G8 is an optionally substituted C2-C4 alkylene group.

[0067] 22. The compound according to any one of items 2, 4-11, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that G9 or G 10 Or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl.

[0068] 23. A compound according to any one of items 1 to 22, wherein G5 or G6 or both have one of the following structures:

[0069] 24. The compound according to any one of items 1 to 23, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, which is a compound as shown in Table 1.

[0070] 25. A composition comprising: a therapeutic agent or a preventive agent; and a carrier for delivering the therapeutic agent or the preventive agent, wherein the carrier comprises a cationic lipid, and the cationic lipid comprises one or more of the compound represented by formula (I) described in any one of items 1 to 24, or a pharmaceutically acceptable salt thereof.

[0071] 26. A composition according to item 25, wherein the therapeutic agent or preventive agent is selected from one or more of a nucleic acid molecule, a small molecule compound, a polypeptide or a protein, preferably, wherein the nucleic acid molecule is selected from one or more of single-stranded DNA, double-stranded DNA, a short isomer, agomir, antagomir, antisense molecule, small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicersubstrate RNA (dsRNA), small hairpin RNA (shRNA), transfer RNA (tRNA), messenger RNA (mRNA), locked nucleic acid (LNA), peptide nucleic acid (PNA) or morpholino oligonucleotide.

[0072] 27. The composition according to item 26, wherein the therapeutic or prophylactic agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof. Preferably, the mRNA is a monocistronic mRNA or a polycistronic mRNA.

[0073] 28. The composition according to item 27, wherein the antigen is a pathogenic antigen.

[0074] 29. The composition according to item 26, wherein the mRNA comprises one or more functional nucleotide analogs, wherein the functional nucleotide analogs are selected from one or more of pseudouridine, 1-methyl-pseudouridine or 5-methylcytosine.

[0075] 30. According to item 25, the small molecule compound is selected from one or more of antitumor drugs, anti-infective drugs, local anesthetics, antidepressants, anticonvulsants, antibiotics / antibacterial agents, antifungals, antiparasitic drugs, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, anti-glaucoma agents, anesthetics or imaging agents.

[0076] 31. The composition according to item 25, wherein the mass ratio of the carrier to the therapeutic or preventive agent is 5:1 to 50:1.

[0077] 32. The composition according to claim 25, wherein the composition is a nanoparticle preparation, wherein the average size of the nanoparticle preparation is 10 to 500 nm; or the pKa of the nanoparticles is 4.5 to 8.5.

[0078] 33. A composition according to any one of items 25 to 32, wherein the carrier further comprises or one or more neutral lipids.

[0079] 34. A composition according to claim 33, wherein the neutral lipid is one or more selected from phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, ceramide, sterol and derivatives thereof.

[0080] 35. The composition according to any one of items 25 to 34, wherein the molar ratio of cationic lipid to neutral lipid is 100:1 to 5:1.

[0081] 36. The composition of any one of items 25 to 32, further comprising a steroid, preferably, the steroid is one or more selected from cholesterol, non-sterols, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatine, tomatine, ursolic acid, α-tocopherol, and corticosteroids.

[0082] 37. The composition of any one of items 25 to 36, wherein the molar ratio of cationic lipid to steroid is 2:1 to 4:1.

[0083] 38. A composition according to any one of items 25 to 36, wherein the composition further comprises one or more lipids capable of binding to a polymer, preferably, the lipid capable of binding to a polymer is one or more selected from PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol or PEG-modified dialkylglycerol, further preferably, the molar ratio of the cationic lipid to the lipid capable of binding to a polymer is 100:1 to 20:1.

[0084] 39. According to the composition described in any one of items 25 to 36, the carrier further comprises neutral lipids, structural lipids and polymer-conjugated lipids, and the molar ratio of the cationic lipids, the neutral lipids, the steroid lipids, and the polymer-conjugated lipids is (15-70): (1-15): (15-55): (0-3).

[0085] 40. The composition according to claim 25, characterized in that the composition further comprises a pharmaceutically acceptable excipient, preferably, the excipient comprises a pharmaceutically acceptable diluent.

[0086] 41. Use of a compound of formula (I) as described in any one of items 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition as described in any one of items 25 to 40 in the preparation of a drug, wherein the drug is preferably any one selected from a gene drug, a nucleic acid vaccine, a small molecule drug, a polypeptide or a protein drug.

[0087] 42. Use of a compound of formula (I) as described in any one of items 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition as described in any one of items 25 to 40 in targeting immune cells.

[0088] 43. Use of a compound of formula (I) as described in any one of items 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition as described in any one of items 25 to 40 in the preparation of a drug targeting immune cells.

[0089] 44. The use according to item 42 or 43, wherein the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.

[0090] 45. Use of a compound of formula (I) as described in any one of items 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition as described in any one of items 25 to 40 in promoting cell polarization.

[0091] 46. ​​Use of a compound of formula (I) as described in any one of items 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition as described in any one of items 25 to 40 in the preparation of a drug that promotes immune cell polarization.

[0092] 47. The use according to item 45 or 46, wherein the cell polarization is from M0 type to M1 type polarization.

[0093] 48. The use according to item 45 or 46, wherein the cell polarization is from M2 type to M0 type polarization.

[0094] 49. The use according to item 45 or 46, wherein the cell is a macrophage.

[0095] 50. A method for screening lipid nanoparticles in vitro, comprising:

[0096] The first screening was conducted in macrophage cell lines to obtain lipid nanoparticles that can transfect macrophage cell lines;

[0097] Among the obtained lipid nanoparticles, those with a FLuc fluorescence signal intensity higher than 10,000 RLUs were selected for a second screening in bone marrow-derived primary macrophages;

[0098] The target lipid nanoparticles were obtained after the second screening.

[0099] 51. The method of claim 50, wherein the macrophage cell line is a Raw264.7 cell line.

[0100] 52. A method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising:

[0101] Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene are injected into wild-type mice via the tail vein, and the first lipid nanoparticles expressing CAR-mRNA in a given organ are screened and obtained with an expression ratio higher than 80%.

[0102] Optionally, the first lipid nanoparticles obtained by screening are encapsulated with CAR-mRNA carrying a reporter gene and injected intratumorally into tumor-bearing mice to screen for a second lipid nanoparticle that is expressed only in the tumor site and not in other organs and is stably expressed for 24 to 48 hours;

[0103] The first or second lipid nanoparticles obtained by screening were injected into Cre reporter gene mice through the tail vein to screen for Td tomato in immune cells. + Cell-targeted lipid nanoparticles.

[0104] 53. The method of claim 50, wherein the given organ is selected from the spleen or bone marrow.

[0105] 54. The method according to item 50, wherein the immune cell is selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.

[0106] 55. The method according to any one of items 50-54, wherein the target lipid nanoparticles are prepared from the compound of formula (I) involved in items 1-24 or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof.

[0107] Effects of the Invention

[0108] The cationic lipid compounds and compositions of the present application can be used to deliver nucleic acid drugs or small molecule drugs, enriching the types of cationic lipid compounds and having important significance for the development and application of nucleic acid preventive and therapeutic agents.

[0109] Macrophages constitute the largest immune cell population in the tumor microenvironment and have the ability to penetrate solid tumors and catalyze immune responses. In order to screen LNPs (lipid nanoparticles) that form a variety of CAR-immune cells in vivo, this application first screens macrophages in vitro and then further screens in vivo to obtain LNPs that construct a variety of CAR-immune cells in situ.

[0110] 1. The LNP screening method for in vitro macrophage mRNA delivery provided in this application solves the problems of high primary cell dosage and long primary cell extraction time caused by direct screening of primary macrophages.

[0111] 2. The LNP screening method for in vivo immune cell mRNA delivery provided in this application is simple and has good effects in constructing in situ CAR-immune cell therapy.

[0112] 3. The LNP-mRNA complex provided in this application can deliver mRNA to macrophages with a short transfection time and a simple transfection method. The transfection rate is 30.2%, providing a reference for cell editing methods for adoptive immunotherapy.

[0113] 4. The LNP-mRNA complex provided in this application can deliver circular mRNA and can stably express it for 72 hours.

[0114] 5. Some LNPs provided in this application can polarize unpolarized M0 macrophages into M1 pro-inflammatory phenotype.

[0115] 6. Some LNPs provided in this application can polarize anti-inflammatory and tumor-promoting M2 macrophages into M0 type.

[0116] 7. Some LNPs provided in this application can deliver mRNA to the spleen and bone marrow to produce a variety of CAR-immune cells, including T cells, macrophages, DC cells, and NK cells.

[0117] 8. The in vivo in situ CAR-cells provided in this application have good therapeutic effects in lung metastasis and solid tumor models.

[0118] 9. The LNP preparation method provided in this application is simple and has good reproducibility. The delivered mRNA can be stably expressed in vivo for 48 hours and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0119] The accompanying drawings are provided to facilitate a better understanding of the present application and do not constitute an undue limitation on the present application.

[0120] Figure 1 is a screening flow chart in Example 2.1;

[0121] FIG2 is a diagram showing the screening results of LNPs on Raw264.7 cells in Example 2.6;

[0122] FIG3-1 is a diagram showing the screening results of LNPs on BMDM cells by flow cytometry in Example 2.7;

[0123] Figure 3-2 is a diagram showing the screening transfection efficiency of LNP on BMDM cells in Example 2.7;

[0124] FIG4 is a graph showing the results of LNP No. 43 transfection of CAR-HER2 mRNA into BMDM cells in Example 2.8;

[0125] Figure 5-1 shows the effects of LNPs (43, 43-1) with different transfection efficiencies and RNA packages of different masses on macrophage polarization in Raw264.7 cells in Example 2.9 (fluorescence expression);

[0126] Figure 5-2 shows the effects of LNPs (43, 43-1) with different transfection efficiencies and RNA packages of different masses on macrophage polarization (expressed by iNOS) in Raw264.7 cells in Example 2.9;

[0127] Figure 6-1 shows the polarization effects of different LNPs on BMDM cells in Example 2.10;

[0128] Figure 6-2 shows the polarization effects of different LNPs on BMDM cells in Example 2.10 (statistical results);

[0129] Figure 7 shows that LNPs No. 37 and 43 in Example 2.11 polarize M2-BMDM cells into M0 type;

[0130] Figure 8-1 is a graph showing the killing effect of CAR CD19-BMDM cells on Raji cells (killing ratio) in Example 2.12;

[0131] Figure 8-2 is a graph showing the results of CAR CD19-BMDM cells killing Raji cells in Example 2.12 (fluorescence analysis detection);

[0132] Figure 9 shows the CAR HER2-BMDM cells killing HER2 in Example 2.13 + MC38 cell results diagram;

[0133] Figure 10 is a diagram of CAR HER2-BMDM cells phagocytizing HER2 in Example 2.14. + MC38 cells and HER2 + CT26 cell results diagram;

[0134] Figure 11-1 shows the biodistribution of several LNPs in wild-type B / C mice in Example 2.15 (in vivo);

[0135] Figure 11-2 shows the biodistribution of several LNPs in wild-type B / C mice in Example 2.15 (after dissection);

[0136] Figure 11-3 is a statistical diagram showing the biodistribution of several LNPs in wild-type B / C mice in Example 2.15;

[0137] Figure 12-1 shows the time-dependent signal changes of various LNPs in Example 2.16 in C57 mice bearing wild-type MC38 tumor cells (in vivo);

[0138] Figure 12-2 shows the time-dependent signal changes of various LNPs in Example 2.16 in C57 mice bearing wild-type MC38 tumor cells;

[0139] Figure 13-1 shows the specificity detection results of bone marrow immune cells in Cre transgenic reporter mice in Example 2.17;

[0140] Figure 13-2 shows the specificity detection results of spleen immune cells in Cre transgenic reporter mice in Example 2.17;

[0141] Figure 14 is the HER2 in peripheral blood in Example 2.18 + Cell distribution;

[0142] Figure 15 is a curve showing the body weight changes of mice in the control group (UT) and the treatment group (Treated) in Example 2.19;

[0143] Figure 16 is a graph showing IVIS imaging results of mice in the control group (UT) and the treated group (Treated) in Example 2.19;

[0144] Figure 17 is a quantitative graph of the fluorescence signal of the lungs of mice in the control group (UT) and the treated group (Treated) detected by IVIS in Example 2.19;

[0145] Figure 18 is a survival curve of mice in the control group (UT) and the treatment group (Treated) in Example 2.19;

[0146] Figure 19 is a curve showing the body weight changes of mice in the control group (UT) and the treatment group (Treated) in Example 2.20;

[0147] Figure 20 is a curve showing changes in tumor size in mice in the control group (UT) and the treated group (Treated) in Example 2.20;

[0148] Figure 21 is a graph showing the AST and ALT test results of mice in the control group (UT) and the treatment group (Treated) in Example 2.20;

[0149] Figure 22 is the immunohistochemical analysis of tumors in the control group (UT) and the treated group (Treated) mice in Example 2.21.

[0150] Figure 23 is a flow cytometric analysis of M2 macrophages in the tumor sites of mice in the control group (UT) and the treated group (Treated) in Example 2.21.

[0151] Figure 24 is a flow cytometric analysis of CD4+ cells in the tumor sites of mice in the control group (UT) and the treated group (Treated) in Example 2.21.

[0152] Figure 25 is a flow cytometric analysis of CD8+ cells in the tumor sites of mice in the control group (UT) and the treated group (Treated) in Example 2.21.

[0153] Figure 26 shows the IVIS imaging results of the tumor site 24h, 48h, and 72h after LNP delivery of circular Luc mRNA in Example 2.22. DETAILED DESCRIPTION

[0154] the term

[0155] Unless otherwise described, all technical and scientific terms used in this application have the same meaning as commonly understood by those skilled in the art. For the purpose of interpreting this specification, the following terminology will be used, and where appropriate, terms used in the singular will also include the plural form, and vice versa. All patents, applications, published applications, and other publications are incorporated by reference in their entirety. If any description of a term set forth conflicts with any document incorporated by reference into this application, the terminology set forth below will prevail.

[0156] Unless the context requires otherwise, in this specification and claims, the word "comprise" and variations such as "include" and "contain" are to be construed in an open and inclusive sense, that is, as meaning "including, but not limited to."

[0157] As used herein and unless otherwise indicated, the term "lipid" refers to a group of organic compounds that include, but are not limited to, fatty acid esters and are generally characterized by being poorly soluble in water but soluble in many non-polar organic solvents. Although lipids generally have poor water solubility, certain classes of lipids (e.g., lipids modified with polar groups, such as DMG-PEG2000) have limited water solubility and are soluble in water under certain conditions. Known lipid types include biomolecules such as fatty acids, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, and phospholipids. Lipids can be divided into at least three categories: (1) "simple lipids," which include fats and oils, as well as waxes; (2) "compound lipids," which include phospholipids and glycolipids (e.g., DMG-PEG2000); and (3) "derivatized lipids," such as steroids. In addition, as used herein, lipids also include lipid-like compounds. The term "lipid-like compound," also referred to as "lipidoid," refers to lipid-like compounds (e.g., amphiphilic compounds with lipid-like physical properties).

[0158] As used herein and unless otherwise indicated, the term "lipid nanoparticle" or "LNP" refers to a particle with at least one nanometer (nm) size (e.g., 1 to 1,000 nm) containing one or more types of lipid molecules. The LNP provided herein may further contain at least one non-lipid payload molecule (e.g., one or more nucleic acid molecules) or a small molecule drug. In some embodiments, the LNP comprises a non-lipid payload molecule partially or completely encapsulated in a lipid shell. Wherein the payload is a negatively charged molecule (e.g., mRNA encoding a viral protein), and the lipid component of the LNP comprises at least one cationic lipid. Without being bound by theory, it is expected that cationic lipids can interact with negatively charged payload molecules and promote the incorporation and / or encapsulation of payload into the LNP during LNP formation. Other lipids that can form a part for the LNP provided herein include, but are not limited to, neutral lipids and charged lipids, such as steroids or their analogs, polymer-bound lipids, and various zwitterionic lipids.

[0159] As used herein and unless otherwise indicated, term: " cationic lipid " refers to a lipid that can be positively charged. Exemplary cationic lipids include one or more positively charged amine groups. Preferred cationic lipids are ionizable, so that they can exist in positively charged form or neutral form according to pH value. The ionization of cationic lipids affects the surface charge of lipid nanoparticles under different pH conditions. This charge state can affect plasma protein absorption, blood clearance and tissue distribution (Semple, SC et al., Adv Drug Deliv Rev 32:3-17 (1998)) and the ability (Hafez, IM et al., Gene Ther 8:1188-1196 (2001)) of forming endosomal dissolution (endosomolytic) non-double layer structure, which is crucial for the intracellular delivery of nucleic acid.

[0160] As used herein and unless otherwise indicated, the term "steroid" is a compound comprising the following carbon skeleton:

[0161] Non-limiting examples of steroids include cholesterol and the like.

[0162] As used herein and unless otherwise indicated, the term "neutral lipid" encompasses any lipid molecule that exists in an uncharged form or in a neutral zwitterionic form at a selected pH value or within a selected pH range. In some embodiments, the selected useful pH value or range corresponds to the pH conditions in the environment of the intended lipid use, such as physiological pH. As non-limiting examples, neutral lipids that can be used in conjunction with the present disclosure include, but are not limited to, phosphatidylcholines, such as 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC); phosphatidylethanolamines, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 2-((2,3-bis(oleoyloxy)propyl))dimethylammonio)ethyl hydrogenphosphate (DOCP); sphingomyelin (SM); ceramides; steroids, such as sterols, sterols, and derivatives thereof. The neutral lipids provided herein can be synthetic or derived from (isolated or modified from) natural sources or compounds.

[0163] As used herein and unless otherwise indicated, the term "alkyl" refers to a saturated straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms. In one embodiment, an alkyl group has, for example, one to twenty-four carbon atoms (C1-C24 alkyl), four to twenty carbon atoms (C4-C20 alkyl), six to sixteen carbon atoms (C6-C16 alkyl), six to nine carbon atoms (C6-C9 alkyl), one to fifteen carbon atoms (C1-C15 alkyl), one to twelve carbon atoms (C1-C12 alkyl), one to eight carbon atoms (C1-C8 alkyl) or one to six carbon atoms (C1-C6 alkyl) and is connected to the rest of the molecule by a single bond. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (tert-butyl), 3-methylhexyl, 2-methylhexyl, etc. Unless otherwise indicated, an alkyl group is optionally substituted.

[0164] As used herein and unless otherwise indicated, term " alkenyl " refers to the straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, which contains one or more carbon-carbon double bonds. It will be appreciated by those skilled in the art that term " alkenyl " also includes groups with " cis " and " trans " configurations, or with " E " and " Z " configurations. In one embodiment, alkenyl has, for example, two to twenty-four carbon atoms (C2-C24 alkenyl), four to twenty carbon atoms (C4-C20 alkenyl), six to sixteen carbon atoms (C6-C16 alkenyl), six to nine carbon atoms (C6-C9 alkenyl), two to fifteen carbon atoms (C2-C15 alkenyl), two to twelve carbon atoms (C2-C12 alkenyl), two to eight carbon atoms (C2-C8 alkenyl) or two to six carbon atoms (C2-C6 alkenyl) and it is connected to the remainder of the molecule by a single bond. Examples of alkenyl groups include, but are not limited to, vinyl, prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl, etc. Unless otherwise specified, alkenyl groups are optionally substituted.

[0165] As used herein and unless otherwise indicated, the term "alkynyl" refers to a straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing one or more carbon-carbon triple bonds. In one embodiment, an alkynyl group has, for example, two to twenty-four carbon atoms (C2-C24 alkynyl), four to twenty carbon atoms (C4-C20 alkynyl), six to sixteen carbon atoms (C6-C16 alkynyl), six to nine carbon atoms (C6-C9 alkynyl), two to fifteen carbon atoms (C2-C15 alkynyl), two to twelve carbon atoms (C2-C12 alkynyl), two to eight carbon atoms (C2-C8 alkynyl) or two to six carbon atoms (C2-C6 alkynyl) and is connected to the rest of the molecule by a single bond. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, pentynyl, etc. Unless otherwise indicated, an alkynyl group is optionally substituted.

[0166] As used herein and unless otherwise indicated, the term "cyclization" refers to partial or complete connection within or between molecules to form a cyclic molecular structure. The connection points may be, but are not limited to, one C or N or several C or N groups. The cyclized molecular structure may be saturated or unsaturated. Unless otherwise indicated, the cyclized molecular portion is optionally substituted.

[0167] When a group described herein is referred to as "substituted," it may be substituted with one or more suitable substituents. Illustrative examples of substituents include, but are not limited to, those found in the exemplary compounds and embodiments provided herein, as well as: halogen atoms, such as F, Cl, Br, or I; cyano; oxo (=O); hydroxyl (-OH); alkyl; alkenyl; alkynyl; cycloalkyl; aryl; -(C=O)OR'; -O(C=O)R'; -C(=O)R'; -OR'; -S(O) x R';-S-SR';-C(=O)SR';-SC(=O)R';-NR'R';-NR'C(=O)R';-C(=O)NR'R';-NR'C(=O)NR'R';-OC(=O)NR'R';-NR'C(=O)OR';-NR'S(O) x NR'R';-NR'S(O) x R'; and -S(O) x NR'R', wherein: R' at each occurrence is independently H, C1-C15 alkyl or cycloalkyl, and x is 0, 1 or 2.

[0168] As used herein and unless otherwise indicated, the term "optionally" or "optionally" (e.g., optionally substituted) means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "optionally substituted alkyl" means that the alkyl group may or may not be substituted, and that the description includes both substituted alkyl groups and alkyl groups without substitution.

[0169] The term "prodrug" refers to a derivative of a compound or nucleic acid drug of the present application that can be provided directly or indirectly after being applied to a patient. The prodrug of a composition can be prepared by modifying the functional group present in a compound or nucleic acid (DNA, ASO, siRNA, mRNA, tRNA) in such a way that the modification can be cleaved in a conventional operation or in vivo to obtain a parent compound or nucleic acid. Particularly preferred prodrugs are compounds and nucleic acid drugs (e.g., more easily absorbed into the blood) that can improve the bioavailability of the composition of the present application when administered to a patient, or compounds and nucleic acid drugs that promote the delivery of the parent compound to the site of action (e.g., lymphatic system). Unless otherwise noted, all prodrug forms of the compound of the present application are within the scope of the present application, and various prodrug forms are well known in the art.

[0170] As used herein, and unless otherwise indicated, the term "pharmaceutically acceptable salt" includes both acid addition salts and base addition salts.

[0171] Examples of pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; and organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, benzo ... acid), dodecyl sulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxoglutaric acid, glycerophosphate, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and the like.

[0172] Examples of pharmaceutically acceptable base addition salts include, but are not limited to, salts prepared by adding an inorganic base or an organic base to a free acid compound. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. In one embodiment, the inorganic salt is an ammonium salt, a sodium salt, a potassium salt, a calcium salt, and a magnesium salt. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines; substituted amines, including naturally occurring substituted amines; cyclic amines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, deanol, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like.

[0173] The compound provided herein may contain one or more asymmetric centers, and therefore enantiomers, diastereomers and other stereoisomeric forms may be produced, which may be defined as (R)- or (S)- or as (D)- or (L)- for amino acids according to absolute stereochemistry. Unless otherwise indicated, the compound provided herein is intended to include all such possible isomers, as well as racemic and optically pure forms thereof. When the compound described herein contains olefinic double bonds or other geometric asymmetric centers, unless otherwise indicated, the compound is intended to include E and Z geometric isomers. Similarly, all tautomeric forms are also intended to be included.

[0174] As used herein and unless otherwise indicated, the term "isomer" refers to different compounds having the same molecular formula. "Stereoisomers" are isomers that differ only in the arrangement of their atoms in space. "Atropisomers" are stereoisomers resulting from hindered rotation about a single bond. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A mixture of a pair of enantiomers in any proportion is referred to as a "racemic" mixture. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.

[0175] "Stereoisomers" may also include E and Z isomers or mixtures thereof, as well as cis and trans isomers or mixtures thereof. In certain embodiments, the compounds described herein are isolated as E or Z isomers. In other embodiments, the compounds described herein are mixtures of E and Z isomers.

[0176] The term "nucleic acid" refers to a nucleotide polymer of any length, and includes, for example, DNA and RNA. Nucleotides may be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. Nucleic acids may be in single-stranded or double-stranded form. As used herein and unless otherwise indicated, "nucleic acid" also includes nucleic acid mimics such as locked nucleic acids (LNA), peptide nucleic acids (PNA), and morpholino nucleic acids. As used herein, "oligonucleotide" refers to a short synthetic polynucleotide, generally but not necessarily less than about 200 nucleotides in length. The terms "oligonucleotide" and "polynucleotide" are not mutually exclusive. The above description of polynucleotides is equally and fully applicable to oligonucleotides. Unless otherwise indicated, the left-hand end of any single-stranded polynucleotide sequence disclosed herein is the 5' end; the left-hand direction of a double-stranded polynucleotide sequence is referred to as the 5' direction. The direction of 5′ to 3′ addition of the nascent RNA transcript is called the transcription direction; the sequence region on the DNA strand that has the same sequence as the RNA transcript and is located at the 5′ end relative to the 5′ end of the RNA transcript is called the “upstream sequence”; the sequence region on the DNA strand that has the same sequence as the RNA transcript and is located at the 3′ end relative to the 3′ end of the RNA transcript is called the “downstream sequence”.

[0177] " Isolated nucleic acid " refers to nucleic acid, such as RNA, DNA or mixed nucleic acid, that is substantially separated from other genomic DNA sequences and proteins or complexes (such as ribosomes and polymerases) that naturally accompany native sequences. The nucleic acid molecule of " separation " is a nucleic acid molecule separated from other nucleic acid molecules that are present in the natural source of nucleic acid molecule. In addition, when manufactured by recombinant technology, the nucleic acid molecule of " separation ", such as mRNA molecule, can be substantially free of other cell materials or culture medium, or when chemically synthesized, it can be substantially free of chemical precursors or other chemicals. In specific embodiments, one or more nucleic acid molecules of encoding antigens described herein are separated or purified. The term includes nucleic acid sequences removed from its naturally occurring environment, and includes recombinant or cloned DNA or RNA isolates and chemically synthesized analogs or analogs biosynthesized by heterologous systems. Substantially pure molecules can include isolated forms of molecules.

[0178] The term "coding nucleic acid" or its grammatical equivalents when used to refer to a nucleic acid molecule includes: (a) a nucleic acid molecule that can be transcribed to produce mRNA and then translated into peptides and / or polypeptides when in its natural state or manipulated by methods well known to those skilled in the art; and (b) the mRNA molecule itself. The antisense strand is the complementary sequence of such a nucleic acid molecule, and the coding sequence can be inferred therefrom. The term "coding region" refers to the portion of a coding nucleic acid sequence that is translated into a peptide or polypeptide. The term "untranslated region" or "UTR" refers to the portion of a coding nucleic acid that is not translated into a peptide or polypeptide. Depending on the orientation of the UTR relative to the coding region of the nucleic acid molecule, the UTR is referred to as a 5'-UTR if it is located at the 5' end of the coding region, and as a 3'-UTR if it is located at the 3' end of the coding region.

[0179] As used herein, the term "mRNA" refers to a messenger RNA molecule comprising one or more open reading frames (ORFs), which can be translated by a cell or organism having the mRNA to produce one or more peptide or protein products. The region containing one or more ORFs is referred to as the coding region of the mRNA molecule. In certain embodiments, the mRNA molecule further comprises one or more untranslated regions (UTRs).

[0180] In certain embodiments, the mRNA is a monocistronic mRNA comprising only one ORF. In certain embodiments, the monocistronic mRNA encodes a peptide or protein comprising at least one epitope of a selected antigen (e.g., a pathogenic antigen or a tumor-associated antigen). In other embodiments, the mRNA is a polycistronic mRNA comprising two or more ORFs. In certain embodiments, the polycistronic mRNA encodes two or more peptides or proteins that may be identical or different from each other. In certain embodiments, each peptide or protein encoded by the polycistronic mRNA comprises at least one epitope of a selected antigen. In certain embodiments, the different peptides or proteins encoded by the polycistronic mRNA each comprise at least one epitope of a different antigen. In any one of the embodiments described herein, the at least one epitope may be at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 epitopes of an antigen.

[0181] The term "nucleobase" encompasses purines and pyrimidines, including the natural compounds adenine, thymine, guanine, cytosine, uracil, inosine, and natural or synthetic analogs or derivatives thereof.

[0182] As used herein, the term "functional nucleotide analogue" refers to a modified version of a classical nucleotide A, G, C, U, or T that (a) retains the base pairing properties of the corresponding classical nucleotide and (b) contains at least one chemical modification of the (i) nucleobase, (ii) sugar group, (iii) phosphate group, or (iv) any combination of (i) to (iii) of the corresponding natural nucleotide. As used herein, base pairing encompasses not only the classical Watson-Crick adenine-thymine, adenine-uracil, or guanine-cytosine base pairs, but also base pairs formed between a classical nucleotide and a functional nucleotide analogue, or between a pair of functional nucleotide analogues, wherein the arrangement of hydrogen bond donors and hydrogen bond acceptors allows hydrogen bonds to form between the modified nucleobase and the classical nucleobase, or between two complementary modified nucleobase structures. For example, a functional analogue of guanosine (G) retains the ability to base pair with cytosine (C) or a functional analogue of cytosine. An example of such non-classical base pairing is base pairing between modified nucleotides inosine and adenine, cytosine or uracil. As described herein, functional nucleotide analogs can be naturally occurring or non-naturally occurring. Therefore, nucleic acid molecules containing functional nucleotide analogs can have at least one modified nucleobase, sugar group and / or internucleoside linkage. The application provides exemplary chemical modifications to the nucleobase, sugar group or internucleoside linkage of nucleic acid molecules.

[0183] As used herein, the terms "translational enhancer element," "TEE," and "translational enhancer" refer to regions in nucleic acid molecules that promote translation of a coding sequence of a nucleic acid into a protein or peptide product, such as via cap-dependent or cap-independent translation. TEEs are typically located in the UTR region of a nucleic acid molecule (e.g., mRNA) and enhance the translation level of a coding sequence located upstream or downstream. For example, a TEE in the 5'-UTR of a nucleic acid molecule may be located between the promoter and the start codon of the nucleic acid molecule. Various TEE sequences are known in the art (Wellensiek et al., Genome-wide profiling of human cap-independent translation-enhancing elements, Nature Methods, August 2013; 10(8):747-750; Chappell et al., PNAS, June 29, 2004, 101(26)9590-9594). Some TEEs are known to be conserved across multiple species (Pánek et al., Nucleic Acids Research, Vol. 41, No. 16, Sept. 1, 2013, pp. 7625-7634).

[0184] As used herein, the term "peptide" refers to a polymer containing from two to fifty (2-50) amino acid residues linked by one or more covalent peptide bonds. The term applies to naturally occurring amino acid polymers as well as amino acid polymers in which one or more amino acid residues are non-naturally occurring amino acids (e.g., amino acid analogs or non-natural amino acids).

[0185] The terms "polypeptide" and "protein" are used interchangeably herein to refer to a polymer having more than fifty (50) amino acid residues linked by covalent peptide bonds. That is, a description of a polypeptide equally applies to a description of a protein, and vice versa. The terms apply to naturally occurring amino acid polymers as well as amino acid polymers in which one or more amino acid residues is a non-naturally occurring amino acid (e.g., an amino acid analog). As used herein, the terms encompass amino acid chains of any length, including full-length proteins (e.g., antigens).

[0186] The term "antigen" refers to a substance that can be recognized by a subject's immune system (including the adaptive immune system) and can trigger an immune response (including an antigen-specific immune response) after the subject contacts the antigen. In certain embodiments, the antigen is a protein associated with a diseased cell, such as a cell infected with a pathogen or a neoplastic cell (e.g., a tumor-associated antigen (TAA)).

[0187] An "epitope" is a site on the surface of an antigen molecule that binds to a single antibody molecule, such as a localized area on an antigen surface that is capable of binding to one or more antigen-binding regions of an antibody and that has antigenic or immunogenic activity in an animal, such as a mammal (e.g., a human), and is capable of eliciting an immune response. An epitope with immunogenic activity is a portion of a polypeptide that elicits an antibody response in an animal. An epitope with antigenic activity is a portion of a polypeptide that is bound by an antibody as determined by any method known in the art, including, for example, immunoassays. An antigenic epitope is not necessarily immunogenic. An epitope is typically composed of chemically active surface groups of a molecule, such as amino acids or sugar side chains, and has specific three-dimensional structural characteristics and specific charge characteristics. Antibody epitopes can be linear or conformational. Linear epitopes are formed by continuous amino acid sequences in proteins. Conformational epitopes are formed by amino acids that are discontinuous in the protein sequence but bind together when the protein folds into its three-dimensional structure. Inducible epitopes are formed when the three-dimensional structure of a protein assumes an altered conformation, such as after activation or binding by another protein or ligand. In certain embodiments, an epitope is a three-dimensional surface feature of a polypeptide. In other embodiments, an epitope is a linear feature of a polypeptide. Generally, an antigen has several or many different epitopes and can react with many different antibodies.

[0188] Lipid composition

[0189] In one embodiment, the present application provides a compound of formula (I):

[0190] or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein:

[0191] The G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group;

[0192] The L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-;

[0193] R a and R b are each independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;

[0194] x is 0, 1, or 2;

[0195] Said G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene group;

[0196] The L3 and L4 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c)O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-;

[0197] R c and R d are each independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;

[0198] i is 0, 1, or 2;

[0199] Said G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkyl group or an optionally substituted C2-C24 straight chain alkenyl group;

[0200] The Z is an optionally substituted C1-C12 alkylene, an optionally substituted -R e G7R f -;

[0201] Among them, R e and R f is an optionally substituted C1-C12 alkylene group;

[0202] G7-NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-;

[0203] R g is an optionally substituted C1-C12 alkylene group;

[0204] Said X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G1L1G3L3G5, or X, Z together with the nitrogen to which they are attached form a ring;

[0205] Preferably, Z is an optionally substituted C1-C12 alkylene group, and the compound is of the structure of formula (IA):

[0206] wherein G1, G2, G3, G4, G5, G6, L1, L2, L3, L4, X and Y are as defined in formula (I), and G8 is an optionally substituted C1-C12 alkylene group.

[0207] or preferably, optionally substituted -R e G7R f -, the compound has the structure shown in formula (IB):

[0208] Among them, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e 、R f, X and Y are as defined in formula (I); preferably, G1 and G2 are unsubstituted C2-C4 alkylene, and L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R fis an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0209] Preferably, L1 and L2 are -C(=O)O-, G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0210] Preferably, G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group, and G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b are each independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; said L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and Rf is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0211] Preferably, L3 and L4 are a bond or -OC(=O)O-, said G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; said L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; x is 0, 1 or 2; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R gis an optionally substituted C1-C12 alkylene group; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0212] Preferably, L3 and L4 are bonds, G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; x is 0, 1 or 2; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0213] Preferably, G5 and G6 are optionally substituted C4-C16 straight chain alkenyl groups, G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said Z is optionally substituted C1-C12 alkylene, optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NRg -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0214] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; Rc and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group.

[0215] In a specific embodiment, X and Y are each independently -G1L1G3L3G5; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NRc C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group.

[0216] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R bEach of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group.

[0217] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NRb -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, an optionally substituted C1-C12 alkyl group or an optionally substituted C1-C12 alkenyl group; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group.

[0218] In a specific embodiment, Z is C2-C4 alkylene, G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, optionally substituted C2-C24 straight-chain alkenyl; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl, -G1L1G3L3G5 or X, Z together with the nitrogen to which they are attached form a ring.

[0219] In a specific embodiment, Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R dEach is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, optionally substituted C2-C24 straight-chain alkenyl; X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl, -G1L1G3L3G5 or X, Z together with the nitrogen to which they are attached form a ring.

[0220] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; Rc and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0221] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R dEach is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0222] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R dEach is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0223] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R dEach is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0224] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c)O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0225] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR cC(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0226] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NRc C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0227] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i-, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0228] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are attached, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b Each of them is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; x is 0, 1 or 2; G3 and G4 are each independently a bond, optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i-, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0229] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0230] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、 -NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0231] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR cC(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0232] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0233] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R fwherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0234] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f wherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NRc -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0235] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f wherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0236] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f wherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0237] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are attached, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR cC(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0238] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0239] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0240] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR cC(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0241] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0242] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R fwherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0243] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f wherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NRc -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0244] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f wherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0245] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f wherein G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -S(O). i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0246] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are attached, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR cC(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d Each is independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl; i is 0, 1 or 2; said G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0247] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.

[0248] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0249] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, or an optionally substituted C2-C24 straight-chain alkenyl.

[0250] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, or an optionally substituted C2-C24 straight-chain alkenyl.

[0251] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0252] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0253] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0254] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0255] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0256] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0257] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0258] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0259] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0260] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0261] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0262] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0263] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0264] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0265] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0266] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0267] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0268] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.

[0269] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0270] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0271] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0272] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0273] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0274] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.

[0275] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0276] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, or an optionally substituted C2-C24 straight-chain alkenyl.

[0277] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, or an optionally substituted C2-C24 straight-chain alkenyl.

[0278] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0279] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0280] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0281] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0282] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0283] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.

[0284] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0285] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, or an optionally substituted C2-C24 straight-chain alkenyl.

[0286] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, or an optionally substituted C2-C24 straight-chain alkenyl.

[0287] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0288] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0289] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0290] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl, an optionally substituted C2-C24 straight-chain alkenyl.

[0291] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, an optionally substituted C2-C24 straight-chain alkenyl group.

[0292] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0293] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0294] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0295] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0296] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0297] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -Re G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0298] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0299] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0300] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0301] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0302] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0303] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0304] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0305] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0306] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0307] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0308] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0309] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0310] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0311] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0312] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0313] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0314] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0315] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, Re and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0316] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0317] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0318] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0319] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0320] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0321] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0322] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0323] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0324] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0325] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0326] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0327] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0328] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0329] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0330] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0331] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0332] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0333] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R eand R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0334] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0335] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0336] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0337] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0338] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0339] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0340] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0341] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0342] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0343] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0344] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0345] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0346] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0347] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0348] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0349] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0350] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0351] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0352] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0353] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0354] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0355] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0356] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0357] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0358] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0359] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocyclic alkane)-; said G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; said L1 and L2 are each independently -C(=O)O-; said G3 and G4 are a bond or unsubstituted C2-C4 alkylene; said L3 and L4 are each independently a bond; and said G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0360] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0361] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0362] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0363] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring; G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0364] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0365] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.

[0366] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0367] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0368] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0369] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0370] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0371] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0372] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0373] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0374] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.

[0375] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0376] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0377] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0378] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0379] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0380] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0381] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0382] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0383] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0384] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0385] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0386] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0387] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0388] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0389] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0390] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0391] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0392] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, Z is C2-C4 alkylene; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0393] In a specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl, Y is -G1L1G3L3G5, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0394] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl, and Z is a C2-C4 alkylene; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0395] In a specific embodiment, X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0396] In a specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0397] In a specific embodiment, X is an optionally substituted C1-C3 straight chain alkyl, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f is an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0398] In a specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight chain alkyl, and Z is an optionally substituted -R e G7R f -, R e and R fis an optionally substituted C2-C4 alkylene, G7 is -(3-7 membered heterocycloalkane)-; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.

[0399] In a specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z, together with the nitrogen to which they are connected, form a ring; G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group; L3 and L4 are each independently a bond; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.

[0400] More preferably, the compound has a structure represented by formula (IA-1):

[0401] wherein m is 1 or 3, n is 0 or 1, G5 and G6 are optionally substituted C4-C16 straight chain alkenyl groups, G8 is defined as in formula (IA), G9 and G 10 is an optionally substituted C1-C5 straight-chain alkane.

[0402] Alternatively, the compound has a structure shown in formula (IA-2):

[0403] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.

[0404] Alternatively, the compound has a structure shown in formula (IA-3):

[0405] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.

[0406] Alternatively, the compound has a structure shown in formula (IA-4):

[0407] wherein G1, G2, G3, G4, G5, G6, L1, L2, L3, L4 and Y are as defined in the compound shown in (I); and G8 is an optionally substituted C1-C12 alkylene group.

[0408] Alternatively, the compound has a structure shown in formula (IA-5):

[0409] wherein m is 1 or 3, n is 0 or 1, Y, G5 and G6 are as defined in the compound shown in (I); and G8 is an optionally substituted C1-C12 alkylene group.

[0410] Alternatively, the compound has a structure shown in formula (IA-6):

[0411] wherein m is 1 or 3, n is 0 or 1, and Y, G5 and G6 are as defined in the compound shown in (I).

[0412] Alternatively, the compound has a structure shown in formula (IB-1):

[0413] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.

[0414] Alternatively, the compound has a structure shown in formula (IB-2):

[0415] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.

[0416] Alternatively, the compound has a structure shown in formula (IB-3):

[0417] Alternatively, the compound has a structure shown in formula (IB-1):

[0418] Among them, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e and R f As defined in the compound shown in (I).

[0419] wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.

[0420] More preferably, G8 is optionally substituted C2-C4 alkylene;

[0421] More preferably, G9 or G 10 or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl;

[0422] More preferably, G5 or G6 or both have one of the following structures:

[0423] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocycloalkane)-; X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0424] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocycloalkane)-; X and Y are each independently an optionally substituted C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0425] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight chain alkyl or -G1L1G3L3G5.

[0426] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight chain alkyl or -G1L1G3L3G5.

[0427] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight chain alkyl or -G1L1G3L3G5, with the proviso that X and Y are not both C1-C4 straight chain alkyl or -G1L1G3L3G5.

[0428] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently a C1-C4 straight-chain alkyl substituted with a hydroxyl group or an amino group or -G1L1G3L3G5, provided that X and Y are not both C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0429] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X is a C1-C4 straight-chain alkyl, and Y is a C1-C4 straight-chain alkyl substituted with a hydroxyl group.

[0430] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X is G1L1G3L3G5, and Y is an amino-substituted C1-C4 straight-chain alkyl.

[0431] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently a C1-C4 straight-chain alkyl.

[0432] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently G1L1G3L3G5.

[0433] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently an optionally substituted C12-C16 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocycloalkane)-; X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0434] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently an optionally substituted C12-C16 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocycloalkane)-; X and Y are each independently an optionally substituted C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0435] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently an optionally substituted C12-C16 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight chain alkyl or -G1L1G3L3G5.

[0436] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight chain alkyl or -G1L1G3L3G5.

[0437] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight chain alkyl or -G1L1G3L3G5, with the proviso that X and Y are not both C1-C4 straight chain alkyl or -G1L1G3L3G5.

[0438] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently a C1-C4 straight-chain alkyl substituted with a hydroxyl group or an amino group or -G1L1G3L3G5, provided that X and Y are not both C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0439] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X is a C1-C4 straight-chain alkyl, and Y is a C1-C4 straight-chain alkyl substituted with a hydroxyl group.

[0440] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X is G1L1G3L3G5, and Y is an amino-substituted C1-C4 straight-chain alkyl.

[0441] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight-chain alkenyl; Z is an optionally substituted C2-C4 alkylene; and X and Y are each independently a C1-C4 straight-chain alkyl.

[0442] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently an optionally substituted C12-C16 straight chain alkenyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently G1L1G3L3G5.

[0443] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently a C12-C16 straight chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocycloalkane)-; X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

[0444] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently a C12-C16 straight chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene, an optionally substituted -R e G7R f -; among them, R e and R f is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocycloalkane)-; X and Y are each independently an optionally substituted C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0445] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond or an optionally substituted C2-C4 straight-chain alkylene; L3 and L4 are each independently a bond or -OC(=O)O-; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0446] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently an optionally substituted C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0447] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl group; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently an optionally substituted C1-C4 straight-chain alkyl group or -G1L1G3L3G5, with the proviso that X and Y are not both C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.

[0448] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently a C1-C4 straight-chain alkyl substituted with a hydroxyl group or an amino group or -G1L1G3L3G5, with the proviso that X and Y are not both C1-C4 straight-chain alkyl or -G1L1G3L3G5.

[0449] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X is a C1-C4 straight-chain alkyl, and Y is a C1-C4 straight-chain alkyl substituted with a hydroxyl group.

[0450] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X is G1L1G3L3G5, and Y is a C1-C4 straight-chain alkyl substituted with an amino group.

[0451] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; and X and Y are each independently a C1-C4 straight-chain alkyl.

[0452] In a specific embodiment, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X and Y are each independently G1L1G3L3G5.

[0453] In a specific embodiment, when polarized from M0 type to M1 type, the compound of formula (I) is wherein G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl group substituted with a C2-C4 alkyl group; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently a C1-C4 straight-chain alkyl group substituted with a hydroxyl group or an amino group, or -G1L1G3L3G5, provided that X and Y are not both C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.

[0454] In a specific embodiment, when polarized from M0 type to M1 type, the compound of formula (I) is wherein G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X is a C1-C4 straight-chain alkyl, and Y is a C1-C4 straight-chain alkyl substituted with a hydroxyl group.

[0455] In a specific embodiment, when polarized from M2 type to M0 type, the compound of formula (I) is wherein, G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; X is G1L1G3L3G5, and Y is a C1-C4 straight-chain alkyl substituted with an amino group.

[0456] In a specific embodiment, when polarized from M2 type to M0 type, the compound of formula (I) is wherein G1 and G2 are each independently an optionally substituted C2 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently a bond; L3 and L4 are each independently a bond; G5 and G6 are each independently a C12-C16 straight-chain alkenyl substituted with a C2-C4 alkyl; Z is an optionally substituted C2-C4 alkylene; and X and Y are each independently G1L1G3L3G5.

[0457] The present application provides the following compounds in Table 1 or their pharmaceutically acceptable salts, prodrugs or stereoisomers:

[0458] Table 1 Representative compounds

[0459] The present application further provides a composition comprising a therapeutic agent or a prophylactic agent; and a carrier for delivering the therapeutic agent or the prophylactic agent, wherein the carrier comprises a cationic lipid, and the cationic lipid comprises one or more of the cationic lipid compounds provided in any of the above applications, or their pharmaceutically acceptable salts.

[0460] In the composition of the present application, the therapeutic agent or preventive agent can be a nucleic acid molecule, a small molecule compound, a polypeptide or a protein, or a mixture of two or more thereof.

[0461] In a specific embodiment, the nucleic acid molecule is selected from single-stranded DNA, double-stranded DNA, short isomers, agomir, antagomir, antisense molecules, small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicersubstrate RNA (dsRNA), small hairpin RNA (shRNA), transfer RNA (tRNA), messenger RNA (mRNA) and other forms of RNA molecules known in the art, or nucleic acid mimics such as locked nucleic acid (LNA), peptide nucleic acid (PNA) and morpholino oligonucleotides.

[0462] In a specific embodiment, the therapeutic agent or preventive agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof. Preferably, the mRNA is a monocistronic mRNA or a polycistronic mRNA.

[0463] In a specific embodiment, the antigen is a pathogenic antigen.

[0464] In a specific embodiment, the mRNA contains one or more functional nucleotide analogs. Preferably, the functional nucleotide analogs are selected from one or more of pseudouridine, 1-methyl-pseudouridine or 5-methylcytosine.

[0465] In a specific embodiment, the small molecule compound is selected from one or more of antitumor drugs, anti-infective drugs, local anesthetics, antidepressants, anticonvulsants, antibiotics / antibacterial agents, antifungals, antiparasitic drugs, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, anti-glaucoma agents, anesthetics or imaging agents.

[0466] As described above, in the composition provided by the present application, the amount of the carrier and the therapeutic agent or preventive agent is not limited in this application. In a specific embodiment, the mass ratio of the carrier to the therapeutic agent or preventive agent is 1.5:2 to 50:1, for example, it can be 0.75:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 25:1, 30:1, 35:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, and 49:1.

[0467] In a specific embodiment, the composition of the present application is a nanoparticle preparation, and the average size of the nanoparticle preparation is 10 to 500 nm, for example, it can be 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, or 450 nm.

[0468] In a specific embodiment, the pKa of the nanoparticle preparation of the present application is 4.5-8.5, for example, it can be 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.5, 7, 7.5, 8, 8.1, 8.2, 8.3, or 8.4.

[0469] As described above, the composition provided by the present application, wherein the carrier further comprises one or more neutral lipids, preferably, the neutral lipids are selected from one or more of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, ceramide, sterol and derivatives thereof.

[0470] In a specific embodiment, the molar ratio of the cationic lipid to the neutral lipid is in the range of about 100:1 to about 5:1, for example, it can be 90:1, 85:1, 80:1, 75:1, 70:1, 65:1, 60:1, 55:1, 50:1, 45:1, 40:1, 35:1, 30:1, 25:1, 20:1, 15:1, or 10:1.

[0471] In a specific embodiment, the steroid is one or more selected from cholesterol, non-sterols, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatine, tomatine, ursolic acid, α-tocopherol, and corticosteroids.

[0472] In a specific embodiment, the molar ratio of the cationic lipid to the steroid is in the range of about 2:1 to about 4:1, for example, it can be 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3:1, 3.1:1, 3.2:1, 3.3:1, 3.4:1, 3.5:1, 3.6:1, 3.7:1, 3.8:1, 3.9:1.

[0473] As described above, the composition provided by the present application, wherein the composition carrier further comprises one or more lipids capable of binding to a polymer, preferably, the lipid capable of binding to a polymer is one or more selected from PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol, and PEG-modified dialkylglycerol.

[0474] In a specific embodiment, the molar ratio of the cationic lipid to the lipid capable of binding to the polymer is in the range of about 100:1 to about 20:1, for example, it can be 95:1, 90:1, 85:1, 80:1, 75:1, 70:1, 65:1, 60:1, 55:1, 50:1, 45:1, 40:1, 35:1, 30:1, 25:1.

[0475] In a specific embodiment, in the composition of the present application, the carrier further comprises neutral lipids, structural lipids and polymer-conjugated lipids, and the molar ratio of the cationic lipids, the neutral lipids, the steroid lipids, and the polymer-conjugated lipids is (15-70): (1-15): (15-35): (0-3).

[0476] In a specific embodiment, in the composition of the present application, the carrier further comprises a neutral lipid and a structural lipid, and the molar ratio of the cationic lipid, the neutral lipid, and the steroid lipid is (15-70): (1-15): (15-35).

[0477] In a specific embodiment, the composition further comprises a pharmaceutically acceptable excipient.

[0478] In a specific embodiment, the excipient comprises a pharmaceutically acceptable diluent.

[0479] The present application further provides the use of any of the compounds of formula (I) provided herein, or pharmaceutically acceptable salts, prodrugs or stereoisomers thereof in the preparation of drugs.

[0480] The present application further provides the use of any of the above compositions provided in the present application in the preparation of a drug.

[0481] In a specific embodiment, the drug is any one selected from gene drugs, nucleic acid vaccines, small molecule drugs, polypeptides or protein drugs.

[0482] The present application further provides the use of any compound of formula (I) provided herein, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or any composition provided herein in targeting immune cells.

[0483] The present application further provides the use of any compound of formula (I) provided herein, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or any composition provided herein in the preparation of a drug targeting immune cells.

[0484] In the above use, in a specific embodiment, the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.

[0485] The present application further provides the use of any compound of formula (I) provided herein, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or any composition provided herein in promoting cell polarization.

[0486] The present application further provides the use of any compound of formula (I) provided herein, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or any composition provided herein in the preparation of a drug that promotes immune cell polarization.

[0487] In the use in promoting cell polarization or in preparing a drug for promoting immune cell polarization, in a specific embodiment, the cell polarization is from M0 type to M1 type polarization.

[0488] In the use in promoting cell polarization or in preparing a drug for promoting immune cell polarization, in a specific embodiment, the cell polarization is from M2 type to M0 type polarization.

[0489] In the use in promoting cell polarization or in preparing a medicament for promoting immune cell polarization, in a specific embodiment, the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells, preferably macrophages.

[0490] The present application further provides a method for in vitro screening of lipid nanoparticles, comprising:

[0491] The first screening was conducted in macrophage cell lines to obtain lipid nanoparticles that can transfect macrophage cell lines;

[0492] Among the obtained lipid nanoparticles, those with a FLuc fluorescence signal intensity higher than 10,000 RLUs were selected for a second screening in bone marrow-derived primary macrophages;

[0493] The target lipid nanoparticles were obtained after the second screening.

[0494] In a specific embodiment, the macrophage cell line is the Raw264.7 cell line.

[0495] In a specific embodiment, the FLuc fluorescence signal intensity is higher than 10,000 RLUs and may be higher than 20,000 RLUs, 30,000 RLUs, 40,000 RLUs, 50,000 RLUs, 60,000 RLUs, 70,000 RLUs, 80,000 RLUs, 90,000 RLUs, 100,000 RLUs, 110,000 RLUs, 120,000 RLUs, 130,000 RLUs, 140,000 RLUs, 150,000 RLUs, 160,000 RLUs, 170,000 RLUs, 180,000 RLUs, 190,000 RLUs, 200,000 RLUs and above.

[0496] The present application further provides a method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising:

[0497] Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene are injected into wild-type mice via the tail vein, and the first lipid nanoparticles expressing CAR-mRNA in a given organ are screened and obtained with an expression ratio higher than 80%.

[0498] Optionally, the first lipid nanoparticles obtained by screening are encapsulated with CAR-mRNA carrying a reporter gene and injected intratumorally into tumor-bearing mice to screen for expression of the second lipid nanoparticles only in the tumor site and not in other organs, and stably expressing for 24 to 48 hours; the other organs refer to organs without tumors;

[0499] The first or second lipid nanoparticles obtained by screening were injected into Cre reporter gene mice through the tail vein to screen for Td tomato in immune cells. + Cell-targeted lipid nanoparticles.

[0500] In a specific embodiment, the Td tomato + The more cells there are, the better the lipid nanoparticles obtained by screening are for mRNA delivery to immune cells in vivo, but this application does not limit this. + The cells meet the requirements of the screening method.

[0501] In a specific embodiment, the given organ is selected from the spleen or bone marrow.

[0502] In a specific embodiment, the immune cell is selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.

[0503] In a specific embodiment, the target lipid nanoparticles as described above are prepared from the compound of formula (I) provided in the present application or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof.

[0504] DETAILED DESCRIPTION

[0505] The present application will be further explained below in conjunction with specific embodiments, but these embodiments are only used to illustrate the present application and are not intended to limit the scope of the present application. The implementation conditions adopted in the embodiments can be further adjusted according to the different requirements of specific use, and the implementation conditions not specified are conventional conditions in the industry. The technical features involved in the various embodiments of the present application can be combined with each other as long as they do not conflict with each other.

[0506] In the specific examples of this application, the raw materials used can be obtained commercially.

[0507] Example 1

[0508] Example 1.1 Synthesis of Compound 1

[0509] Synthesis route

[0510] Step 1: Synthesis of intermediate 1-2

[0511] To a solution of geraniol (5 g, 16.86 mmol, 1 eq) and triethylamine (2.33 mL, 16.86 mmol, 1 eq) in dichloromethane (100 mL) was slowly added dropwise p-nitrophenyl chloroformate (4.07 g, 20.03 mmol, 1.2 eq) dissolved in dichloromethane. The reaction mixture was stirred at room temperature for 3 h to terminate the reaction, extracted with water, and the combined organic layers were dried over MgSO4 and the solvent removed in vacuo to afford crude product 1-1. To a 250 mL round-bottom flask containing crude product 1-1 were added hydroxyethyl acrylate (2.11 g, 20.03 mmol, 1.2 eq), potassium carbonate (2.76 g, 20.03 mmol, 1.2 eq), and N,N-dimethylformamide solvent (200 mL). The mixture was stirred at 80°C for 3 h. TLC indicated the complete disappearance of compound 1-1. After removing DMF in vacuo, washing with brine, the combined organic layers were dried over MgSO4, and the solvent was removed in vacuo to give a crude product. The crude product was purified by column chromatography (eluent: PE / EA=10 / 1), and the pure product fractions were evaporated to give a slightly yellow oily compound 1-2 (10.06 g, 69%). 1H NMR (400MHz, CDCl3) δ6.44(dt,J=17.4,1.2Hz,1H),6.14(ddd,J=17.3,10.4,1.0Hz,1H),5.86(dt,J=10.5,1.2Hz,1H),5.45–5.33(m,1H ),5.07(dt,J=6.8,3.4Hz,1H),4.68(d,J=7.2Hz,2H),4.39(d,J=1.0Hz,4H),2.13–2.04(m,4H),1.72(s,3H),1.68(s,3H),1.60(s,3H).

[0512] Step 2: Synthesis of compound 1

[0513] N,N-dimethylethylenediamine (30 μL, 0.33 mmol, 1 eq) and compound 1-2 (300 μL, 1.01 mmol, 3 eq) were mixed and stirred at 70 ° C. for 48 h. The mixture was purified by column chromatography (silica gel column, eluent: dichloromethane solution containing 0-10% methanol (volume percentage)) to give compound 1 (370 mg, 54%) as a slightly yellow oil. 1 H NMR (400MHz, CDCl3) δ5.38(t,J=6.6Hz,2H),5.08(s,2H),4.67(d,J=7.2Hz,4H),4.38–4.25(m,8H),2.79(t,J=7.0Hz,4H ),2.63(s,2H),2.49(t,J=6.9Hz,6H),2.35(s,6H),2.12–2.02(m,8H),1.70(d,J=15.9Hz,12H),1.58(d,J=11.9Hz,6H).

[0514] Example 1.2 Synthesis of Compound 2

[0515] Compound 2 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.43–5.27(m,2H),5.08(s,2H),4.67(d,J=7.2Hz,2H), 4.60(dd,J=13.8,7.0Hz,2H),4.28(dt,J=36.3,19.1Hz,6H),2.74(dd,J=21.3 ,14.6Hz,5H),2.62(s,6H),2.44(ddd,J=32.9,16.7,9.9Hz,6H),2.13–2.02( m,8H),1.88(s,2H),1.73–1.67(m,12H),1.60(s,6H),1.27(d,J=12.3Hz,3H).

[0516] Example 1.3 Synthesis of Compound 3

[0517] Compound 3 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.1Hz,4H),5.06(d,J=6.6Hz,4H),4.66(d,J=7.2Hz,8H),4.33–4.28(m,16H),2.78(t,J=7.0 Hz, 9H), 2.49 (dd, J = 22.3, 15.4Hz, 16H), 2.23 (s, 2H), 2.06 (dd, J = 11.6, 6.0Hz, 16H), 1.69 (d, J = 16.1Hz, 24H), 1.59 (s, 12H).

[0518] Example 1.4 Synthesis of Compound 4

[0519] Compound 4 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.31(t,J=7.0Hz,4H),5.00(d,J=6.5Hz,4H),4.60(d,J=7.2Hz,8H),4.24(dd,J=13.2,5.0Hz ,18H),2.68(t,J=6.6Hz,8H),2.39(t,J=6.7Hz,17H),2.09–1.86(m,20H),1.63(d,J=16.2Hz,24H),1.53(s,12H).

[0520] Example 1.5 Synthesis of Compound 5

[0521] Compound 5 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.37(t,J=7.0Hz,3H),5.07(d,J=6.6Hz,3H),4.67(d,J=7.2Hz,6H),4.31(dd,J=13.5,5.6Hz, 12H), 2.75 (t, J = 7.1Hz, 6H), 2.66 (s, 3H), 2.56–2.33 (m, 19H), 2.15–1.99 (m, 14H), 1.73–1.67 (m, 18H), 1.60 (s, 9H).

[0522] Example 1.6 Synthesis of Compound 6

[0523] Compound 6 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.2Hz,2H),5.08(t,J=6.2Hz,2H),4.66(t,J=8.5Hz,4H),4.41–4.24(m,8H),2.87–2.52(m,14H) ,2.43(t,J=6.9Hz,7H),2.12–2.02(m,8H),1.73–1.67(m,12H),1.60(s,6H),1.08(dt,J=36.4,6.0Hz,4H),0.93(d,J=6.5Hz,3H).

[0524] Example 1.7 Synthesis of Compound H77

[0525] Compound 7 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38(t,J=7.2Hz,4H),5.08(t,J=6.3Hz,4H),4.67(d,J=7.2Hz,8H),4.34–4.27(m,16H),2.75 (t,J=7.0Hz,8H),2.46(t,J=7.0Hz,16H),2.31(s,6H),2.16–2.00(m,18H),1.70(d,J=16.4Hz,28H),1.60(s,12H).

[0526] Example 1.8 Synthesis of Compound 8

[0527] Compound 8 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.38(t,J=7.2Hz,2H),5.07(d,J=6.8Hz,2H),4.67(d,J =7.2Hz,4H),4.31(ddd,J=8.2,5.1,2.1Hz,8H),2.75(ddd,J=48.6,13.4,6.5 Hz,4H),2.49–2.41(m,8H),2.30(s,2H),2.07(dd,J=11.8,6.5Hz,8H),1.95( s,2H),1.72–1.67(m,12H),1.60(s,6H),1.52(s,3H),1.27(d,J=12.2Hz,3H).

[0528] Example 1.9 Synthesis of Compound 9

[0529] Compound 9 was prepared by the same method as in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38(t,J=6.9Hz,2H),5.08(t,J=6.6Hz,2H),4.65(d,J=7.2Hz,4H),4.13(dt,J=26.9,5.9Hz,8H),2.79(t,J=7.1Hz,4 H),2.62(d,J=6.6Hz,2H),2.45(t,J=7.1Hz,6H),2.34(s,6H),2.12–2.02(m,8H),1.80–1.72(m,8H),1.70(d,J=15.4Hz,12H),1.60(s,6H).

[0530] Example 1.10 Synthesis of Compound 10

[0531] Compound 10 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(dd,J=7.8,6.6Hz,2H),5.08(t,J=6.7Hz,2H),4.65(d,J=7.2Hz,4H),4.12(dt,J=27.8,6.0Hz,8H),2.75(t,J=7.1Hz, 4H),2.42(dq,J=14.0,7.3Hz,8H),2.31(s,6H),2.14–2.03(m,8H),1.78 –1.72(m,8H),1.72(s,6H),1.68(s,6H),1.67–1.62(m,2H),1.60(s,6H).

[0532] Example 1.11 Synthesis of Compound 11

[0533] Compound 11 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.2Hz,4H),5.08(dd,J=6.7,5.6Hz,4H),4.65(d,J=7.2Hz,8H),4.17–4.06(m,16H),2.78(t,J=7.1Hz,8H),2.72– 2.48(m,8H),2.44(t,J=7.1Hz,8H),2.26(d,J=9.3Hz,3H),2.12–2.02(m, 16H),1.74(s,10H),1.72(d,J=4.3Hz,18H),1.68(s,12H),1.60(s,12H).

[0534] Example 1.12 Synthesis of Compound 12

[0535] Compound 12 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(dd,J=7.2,6.1Hz,4H),5.08(t,J=6.7Hz,4H),4.65(d,J=7.2Hz,8H),4.12(dt,J=28.4,5.9Hz,17H) ,2.74(d,J=6.5Hz,9H),2.42(t,J=7.0Hz,12H),2.16–2.00(m,18H),1.73(dd,J=6.5,3.4Hz,30H),1.68(s,14H),1.60(s,15H).

[0536] Example 1.13 Synthesis of Compound 13

[0537] Compound 13 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.2Hz,3H),5.08(t,J=6.5Hz,3H),4.65(d,J=7.2Hz,6H),4.17–4.07(m,12H),2.75(t,J=7.2Hz ,6H),2.53–2.29(m,20H),2.12–2.02(m,12H),1.78–1.73(m,11H),1.72(s,12H),1.68(s,10H),1.60(s,8H),1.57–1.52(m,2H).

[0538] Example 1.14 Synthesis of Compound 14

[0539] Compound 14 was prepared by the method described in Example 1.1.1 H NMR (400MHz, CDCl3) δ5.38(t,J=7.2Hz,3H),5.09(s,6H),4.67(d,J=7.2Hz,4H),4.31(dd,J=13.6,5.1Hz,12H) ,2.74(t,J=6.7Hz,6H),2.44(dd,J=24.0,17.5Hz,20H),2.12–1.87(m,26H),1.77–1.63(m,22H),1.60(s,18H).

[0540] Example 1.15 Synthesis of Compound 15

[0541] Compound 15 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38(t,J=7.1Hz,4H),5.08(t,J=6.3Hz,4H),4.65(d,J=7.2Hz,8H),4.12(dt,J=28.2,5.6Hz,18H),2. 75(t,J=7.1Hz,8H),2.42(t,J=7.2Hz,16H),2.13–1.99(m,18H),1.73(dd,J=6.2,3.2Hz,30H),1.68(s,15H),1.60(s,15H).

[0542] Example 1.16 Synthesis of Compound 16

[0543] Compound 16 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.2Hz,2H),5.08(t,J=6.6Hz,2H),4.65(d,J=7.2Hz,4H),4.12(dt,J=27.1,5.9Hz,8H),2.87–2.67(m,4H), 2.49–2.34(m,9H),2.14–2.00(m,9H),1.92(dd,J=19.8,12.4Hz,3H),1.79–1.69(m,16H),1.68(s,6H),1.60(s,6H),1.46(d,J=17.4Hz,3H).

[0544] Example 1.17 Synthesis of Compound 17

[0545] Compound 17 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.13–5.03 (m, 2H), 4.31 (dd, J = 11.0, 5.0Hz, 8H), 4.24–4. 15(m,4H),2.80(t,J=7.1Hz,4H),2.64–2.58(m,2H),2.56–2.37(m,8H),2.31(s, 6H),1.97(ddd,J=22.2,14.8,7.3Hz,4H),1.74(dd,J=12.7,7.0Hz,2H),1.68(s ,6H),1.60(s,6H),1.53–1.45(m,2H),1.36–1.15(m,4H),0.92(d,J=6.4Hz,6H).

[0546] Example 1.18 Synthesis of Compound 18

[0547] Compound 18 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.08 (t, J=7.1Hz, 2H), 4.34–4.27 (m, 8H), 4.20 (ddd, J= 14.1,8.4,4.3Hz,4H),2.76(t,J=7.0Hz,4H),2.47(t,J=6.8Hz,6H),2.33(d,J =7.3Hz,2H),2.29(s,6H),2.02–1.92(m,4H),1.73–1.67(m,8H),1.63–1.57(m ,8H),1.50(dd,J=13.3,7.2Hz,2H),1.39–1.12(m,6H),0.92(d,J=6.5Hz,6H).

[0548] Example 1.19 Synthesis of Compound 19

[0549] Compound 19 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.08 (dd, J=7.7, 6.5Hz, 4H), 4.31 (dd, J=11.7, 5.6Hz, 18H), 4.19 (dd,J=13.5,6.5Hz,8H),2.79(t,J=7.1Hz,8H),2.55–2.40(m,16H),1.98(dt,J=14.8,7 .2Hz,8H),1.75–1.69(m,4H),1.68(s,12H),1.60–1.52(m,17H),1.51–1.43(m,4H),1. 34(dt,J=11.7,7.1Hz,4H), 1.20(ddd,J=13.7,8.0,5.4Hz,4H), 0.92(d,J=6.5Hz,12H).

[0550] Example 1.20 Synthesis of Compound 20

[0551] Compound 20 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.08(td,J=7.1,1.2Hz,4H),4.31(dd,J=11.9,5.1Hz,16H),4.19(dd,J=13.7,6.2Hz,8H),2.75(t,J=6.9Hz,8H),2.46(d,J=7. 0Hz,12H),2.23(d,J=42.7Hz,4H),1.98(dt,J=21.3,7.3Hz,8H),1.74–1.6 4(m,20H),1.61–1.49(m,23H),1.37–1.10(m,8H),0.92(d,J=6.5Hz,12H).

[0552] Example 1.21 Synthesis of Compound 21

[0553] Compound 21 was prepared by the method described in Example 1.1. 1 H NMR(400MHz, CDCl3)δ5.08(td,J=7.1,1.2Hz,3H),4.34–4.29(m,12H),4.21–4.16(m,6H),2.74(d,J=7.0Hz,6H),2.49–2.2 5(m,24H),1.98(dt,J=21.2,7.3Hz,6H),1.75–1.67(m,14H),1.60–1.54(m,13H),1.41–1.11(m,6H),0.92(d,J=6.1Hz,9H).

[0554] Example 1.22 Synthesis of Compound 22

[0555] Compound 22 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.08 (t, J=7.1Hz, 2H), 4.34–4.14 (m, 12H), 2.77 (ddd, J=20 .0,13.3,7.0Hz,3H),2.71–2.53(m,9H),2.53–2.37(m,6H),2.04–1.92(m,4H),1 .77–1.70(m,2H),1.68(s,6H),1.60(s,6H),1.58–1.47(m,4H),1.41–1.33(m,3H ),1.26–1.14(m,4H),1.06(dt,J=28.0,7.1Hz,4H),0.92(dd,J=6.5,2.6Hz,9H).

[0556] Example 1.23 Synthesis of Compound 23

[0557] Compound 23 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.08 (t, J=7.0Hz, 4H), 4.31 (dd, J=12.8, 5.8Hz, 16H), 4.22–4.15(m,8H),2.75(t,J=6.9Hz,8H),2.54–2.21(m,21H),1.98(td,J=14 .4,7.3Hz,8H),1.79–1.69(m,5H),1.68(s,12H),1.60(s,14H),1.57–1.44( m,8H),1.28(dddd,J=30.2,23.0,11.5,6.7Hz,12H),0.92(d,J=6.5Hz,12H).

[0558] Example 1.24 Synthesis of Compound 24

[0559] Compound 24 was prepared by the method described in Example 1.1. 1H NMR(400MHz, CDCl3)δ5.08(t,J=7.1Hz,2H),4.35–4.30(m,6H),4.22–4.14(m,4H),2.83–2.67(m,4H),2.54–2.30(m,10H),2.20(s,2H),2.06–1.8 0(m,8H),1.73(td,J=7.6,2.2Hz,3H),1.68(s,6H),1.60(s,7H),1.49(t dd,J=32.3,19.6,12.6Hz,6H),1.35–1.14(m,4H),0.92(d,J=6.5Hz,6H).

[0560] Example 1.25 Synthesis of Compound 25

[0561] Compound 25 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38(t,J=7.2Hz,2H),5.09(s,4H),4.67(d,J=7.2Hz,4H),4.31(dd,J=12.9,5.7Hz,8H),2.79(t,J=7.0Hz,4H),2.6 4(s,2H),2.49(t,J=7.0Hz,6H),2.35(s,6H),2.08(dt,J=16.2,6.9Hz,12H),1.99–1.94(m,4H),1.72(s,6H),1.68(s,6H),1.60(s,12H).

[0562] Example 1.26 Synthesis of Compound 26

[0563] Compound 26 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.42–5.28(m,2H),5.08(s,4H),4.74–4.51(m,4H),4.30(dd,J=15.2,5.7Hz,6H),2.71(d,J=6.5Hz,4H ),2.65–2.37(m,12H),2.31(s,4H),2.12–2.01(m,12H),1.99–1.90(m,4H),1.73–1.65(m,12H),1.59(s,12H),1.28(m,2H).

[0564] Example 1.27 Synthesis of Compound 27

[0565] Compound 27 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.38(t,J=7.2Hz,4H),5.08(s,8H),4.66(d,J=7.2Hz,8H),4.30(dd,J=13.3,5.7Hz,16H),2.78(t,J=7.1Hz,8 H),2.62–2.33(m,16H),2.22(s,3H),2.07(dt,J=22.4,7.8Hz,24H),1.99–1.90(m,8H),1.72(s,12H),1.67(s,12H),1.59(s,24H).

[0566] Example 1.28 Synthesis of Compound 28

[0567] Compound 28 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38(t,J=7.0Hz,4H),5.09(s,8H),4.67(d,J=7.2Hz,8H),4.31(dd,J=13.8,5.6Hz,16H), 2.76(s,8H),2.46(t,J=7.0Hz,11H),2.27(s,3H),2.19–1.87(m,37H),1.78–1.66(m,24H),1.65–1.50(m,28H).

[0568] Example 1.29 Synthesis of Compound 29

[0569] Compound 29 was prepared by the method described in Example 1.1.

[0570] Example 1.30 Synthesis of Compound 30

[0571] Compound 30 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38(s,2H),5.09(s,4H),4.66(d,J=7.0Hz,4H),4.30(d,J=11.8Hz,8H),2.72(dd,J=41.3,32 .6Hz,12H),2.43(d,J=6.6Hz,4H),2.19–1.97(m,18H),1.70(d,J=17.8Hz,12H),1.59(s,12H),1.43–0.89(m,10H).

[0572] Example 1.31 Synthesis of Compound 31

[0573] Compound 31 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.38(t,J=6.8Hz,4H),5.09(s,8H),4.67(d,J=7.2Hz,8H),4.34–4.26(m,16H),2.75(t,J=7.0Hz,8H),2 .46(t,J=7.0Hz,16H),2.31(s,4H),2.15–2.01(m,26H),1.99–1.90(m,8H),1.70(d,J=18.5Hz,27H),1.58(d,J=11.1Hz,27H).

[0574] Example 1.32 Synthesis of Compound 32

[0575] Compound 32 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.38 (dd, J=7.2, 6.1Hz, 2H), 5.10 (dd, J=7.2, 2.5Hz, 4H), 4.67 (d, J=7.2Hz, 4H), 4.36–4. 27(m,8H),2.89–2.60(m,4H),2.49–2.40(m,8H),2.32–1.79(m,24H),1.73–1.67(m,12H),1.61–1.47(m,14H).

[0576] Example 1.33 Synthesis of Compound 33

[0577] The synthetic route is as follows:

[0578] 33.1 Preparation of Intermediate 33-1

[0579] The raw material farnesol (10 g, 45.25 mmol, 1 eq) was dissolved in 50 mL of dichloromethane, and acryloyl chloride (54.30 mmol, 1.2 eq) and triethylamine (67.88 mmol, 1.5 eq) were added dropwise. The reaction was allowed to proceed overnight, and the mixture was purified by column chromatography (PE / EA = 10:1) to obtain intermediate 33-1. 1 H NMR (400MHz, CDCl3) δ6.46–6.34(m,1H),6.12(dd,J=17.3,10.4Hz,1H),5.86–5.76(m,1H),5.40(t,J=7.0Hz,1H),5. 17–5.03(m,2H),4.66(d,J=7.3Hz,2H),2.16–2.03(m,6H),2.00–1.95(m,2H),1.78(s,3H),1.68(s,3H),1.60(s,6H).

[0580] 33.2 Preparation of Compound 33

[0581] N,N-dimethylethylenediamine (32 μL, 0.36 mmol, 1 eq) and compound 33-1 (300 μL, 1.09 mmol, 3 eq) were mixed and stirred at 70°C for 48 h. The mixture was purified by column chromatography (silica gel column, eluent: dichloromethane solution containing 0-10% methanol (volume percentage)) to give compound 33 (380 mg, 60%) as a slightly yellow oil. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.2Hz,2H),5.14–5.04(m,4H),4.56(d,J=7.2Hz,4H),2.79(t,J=7.2Hz,4H),2.60(t,J=7.1 Hz,2H),2.45(t,J=7.2Hz,6H),2.30(s,6H),2.13–2.04(m,12H),1.99–1.95(m,4H),1.76(s,6H),1.68(s,6H),1.60(s,12H).

[0582] Example 1.34 Synthesis of Compound 34

[0583] Compound 34 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.2Hz,2H),5.15–5.04(m,4H),4.56(d,J=7.2Hz,4H),2.75(t,J=7.2Hz,4H),2.48 –2.35(m,8H),2.31(s,6H),2.17–2.04(m,12H),2.00–1.95(m,4H),1.76(s,6H),1.70–1.64(m,8H),1.60(s,12H).

[0584] Example 1.35 Synthesis of Compound 35

[0585] Compound 35 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.33(t,J=6.9Hz,4H),5.09(q,J=6.6Hz,8H),4.56(d,J=7.2Hz,8H),2.78(t,J=7.2H z,8H),2.44(t,J=7.2Hz,15H),2.28–1.91(m,36H),1.76(s,12H),1.68(s,12H),1.58(d,J=12.7Hz,24H).

[0586] Example 1.36 Synthesis of Compound 36

[0587] Compound 36 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.1Hz,4H),5.16–5.04(m,8H),4.56(d,J=7.2Hz,8H),2.75(t,J=7.2Hz,8H) ,2.42(t,J=7.2Hz,12H),2.33–1.93(m,39H),1.76(s,12H),1.69(d,J=9.1Hz,12H),1.58(d,J=12.6Hz,28H).

[0588] Example 1.37 Synthesis of Compound 37

[0589] Compound 37 was prepared by the method described in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.2Hz,3H),5.15–5.03(m,6H),4.56(d,J=7.2Hz,6H),2.75(t,J=7.4Hz,6H),2.45–2.32(m, 14H),2.28(s,6H),2.08(dt,J=15.6,5.8Hz,18H),2.01–1.95(m,6H),1.76(s,9H),1.70–1.64(m,11H),1.63–1.52(m,20H).

[0590] Example 1.38 Synthesis of Compound 38

[0591] Compound 38 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.1Hz,2H),5.15–5.04(m,4H),4.56(d,J=7.2Hz,4H),2.84–2.50(m,10H),2.50–2.15(m,6H),2.13–1.92(m,1 7H), 1.76 (s, 6H), 1.69 (d, J = 9.3Hz, 7H), 1.58 (d, J = 12.8Hz, 14H), 1.43 (d, J = 7.6Hz, 2H), 1.13 (dd, J = 40.4, 33.4Hz, 4H), 0.92 (d, J = 6.5Hz, 2H).

[0592] Example 1.39 Synthesis of Compound 39

[0593] Compound 39 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.2Hz,4H),5.16–5.03(m,8H),4.56(d,J=7.3Hz,8H),2.75(t,J=7.2Hz,8H),2 .40(dd,J=30.4,23.2Hz,20H),2.14–1.91(m,34H),1.77(s,12H),1.69(d,J=9.1Hz,14H),1.64–1.54(m,28H).

[0594] Example 1.40 Synthesis of Compound 40

[0595] Compound 40 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.34(t,J=7.0Hz,2H),5.15–5.04(m,4H),4.56(d,J=7.3Hz,4H),2.76(ddd,J=20.3,13.2,6.3Hz,4H),2.44(d,J=7 .4Hz,8H),2.26(d,J=8.9Hz,3H),2.15–1.86(m,20H),1.77(s,6H),1.69(d,J=9.2Hz,7H),1.60(s,12H),1.48(dd,J=54.9,23.8Hz,2H).

[0596] Example 1.41 Synthesis of Compound 41

[0597] Compound 41 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.33(t,J=7.1Hz,2H),4.59(d,J=7.1Hz,4H),2.80(t,J=7.2Hz,4H),2.61(t,J=7.0Hz,2H),2.46(t,J=7.2Hz,6H),2 .31(s,6H),2.00(t,J=6.5Hz,4H),1.69(s,6H),1.52(dd,J=13.3,6.6Hz,2H),1.42–1.32(m,8H),1.31–1.03(m,28H),0.93–0.77(m,24H).

[0598] Example 1.42 Synthesis of Compound 42

[0599] Compound 42 was prepared by the same method as in Example 1.33. 1H NMR (400MHz, CDCl3) δ5.32(d,J=7.1Hz,2H),4.59(d,J=7.1Hz,4H),2.76(t,J=7.0Hz,4H),2.48–2.33(m,8H),2.30(s,6H),2.0 0(s,4H),1.67(d,J=14.0Hz,8H),1.52(dd,J=13.2,6.6Hz,2H),1.22(ddd,J=34.9,33.1,22.4Hz,36H),0.86(t,J=6.4Hz,24H).

[0600] Example 1.43 Synthesis of Compound 43

[0601] Compound 43 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.32(t,J=7.2Hz,4H),4.60(dd,J=11.5,7.1Hz,8H),2.79(t,J=7.1Hz,8H),2.48(dd,J=34.0,27.0Hz,1 6H),2.28(s,3H),1.99(d,J=6.5Hz,8H),1.69(s,12H),1.52(dt,J=13.2,6.6Hz,4H),1.41–1.03(m,72H),0.97–0.79(m,48H).

[0602] Example 1.44 Synthesis of Compound 44

[0603] Compound 44 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.33(t,J=7.1Hz,4H),4.58(d,J=7.1Hz,8H),2.75(d,J=6.8Hz,8H),2.43(t,J=7.0Hz,12H ),1.99(d,J=6.1Hz,10H),1.69(s,14H),1.53(dt,J=13.2,6.6Hz,6H),1.43–0.96(m,77H),0.92–0.81(m,48H).

[0604] Example 1.45 Synthesis of Compound 45

[0605] Compound 45 was prepared by the same method as in Example 1.33. 1H NMR (400MHz, CDCl3) δ5.32(t,J=7.0Hz,3H),4.58(d,J=7.1Hz,6H),2.76(t,J=7.3Hz,6H),2.40(dd,J=16. 7,7.5Hz,12H),2.30(s,6H),2.00(t,J=6.3Hz,6H),1.69(s,9H),1.59–0.99(m,63H),0.99–0.75(m,36H),

[0606] Example 1.46 Synthesis of Compound 46

[0607] Compound 46 was prepared by the same method as in Example 1.33. 1 H NMR(400MHz, CDCl3) δ5.32(t,J=7.0Hz,2H),4.57(d,J=7.1Hz,4H),4.21–4.15(m,6H),3.62 (t,J=5.2Hz,2H),2.84–2.78(m,2H),2.72–2.58(m,8H),2.44–2.39(m,6H),2.21(td,J=5.2 ,2.5Hz,2H),2.00–1.94(m,6H),1.74(dd,J=7.6,4.5Hz,6H),1.68(s,6H),1.54–1.49(m,2H ),1.41–1.35(m,6H),1.24(dd,J=8.3,4.5Hz,8H),1.15–1.00(m,16H),0.87–0.80(m,24H).

[0608] Example 1.47 Synthesis of Compound 47

[0609] Compound 47 was prepared by the same method as in Example 1.33. 1 H NMR (400MHz, CDCl3) δ5.32(t,J=6.7Hz,4H),4.58(d,J=7.1Hz,8H),2.75(t,J=7.2Hz,8H),2.43( t,J=7.1Hz,20H),2.00(t,J=6.2Hz,8H),1.69(s,12H),1.63–0.98(m,84H),0.92–0.79(m,48H).

[0610] Example 1.48 Synthesis of Compound 48

[0611] Compound 48 was prepared by the same method as in Example 1.33. 1H NMR (400MHz, CDCl3) δ5.32(t,J=7.0Hz,2H),4.58(d,J=7.1Hz,4H),2.82(dd,J=13.9,6.7Hz,2H),2.75–2.6 2(m,2H),2.49–2.29(m,10H),2.00(t,J=6.5Hz,8H),1.69(s,6H),1.56–0.99(m,42H),0.93–0.76(m,24H).

[0612] Example 1.49 Synthesis of Compound 49

[0613] Compound 49 was prepared by the same method as in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(s,2H),4.67(d,J=6.8Hz,4H),4.31(d,J=10.0Hz,8H),2.78(d,J=6.5Hz,4H),2.72(s,2H),2.49(d,J=6.0Hz,8H),1.95 (d,J=45.4Hz,6H),1.71(s,6H),1.52(dd,J=12.4,5.9Hz,2H),1.37(s,10 H),1.27(d,J=11.5Hz,16H),1.16–1.03(m,12H),0.86(t,J=7.1Hz,24H).

[0614] Example 1.50 Synthesis of Compound 50

[0615] Compound H2T750 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.0Hz,2H),4.67(d,J=7.2Hz,4H),4.31(qd,J=6.3 ,2.6Hz,8H),2.74(t,J=6.8Hz,4H),2.49–2.35(m,12H),2.00(t,J=6.6Hz,6H),1.7 1(s,6H),1.53(dd,J=13.3,6.7Hz,2H),1.35(dd,J=14.5,6.1Hz,8H),1.31–1.19(m ,16H),1.09(dddd,J=14.8,12.4,10.5,7.1Hz,14H),0.85(dd,J=8.7,6.7Hz,24H).

[0616] Example 1.51 Synthesis of Compound 51

[0617] Compound 51 was prepared by the method described in Example 1.1.1 H NMR (400MHz, CDCl3) δ5.37(t,J=7.2Hz,4H),4.67(d,J=7.2Hz,8H),4.31(dd, J=13.2,5.7Hz,16H),2.79(t,J=6.9Hz,8H),2.48(s,17H),2.00(t,J=6.2Hz,8 H),1.71(s,12H),1.52(dt,J=13.2,6.6Hz,4H),1.46–1.32(m,18H),1.32–1. 18(m,32H),1.09(dddd,J=14.6,12.1,10.3,7.1Hz,26H),0.90–0.81(m,48H).

[0618] Example 1.52 Synthesis of Compound 52

[0619] Compound 52 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.37 (t, J = 7.2Hz, 4H), 4.67 (d, J = 7.2Hz, 8H), 4.31 (dd, J = 13.9, 5. 6Hz,16H),2.74(s,8H),2.46(t,J=6.7Hz,12H),2.00(d,J=6.4Hz,10H),1.71(s,12H),1 .65(s,6H),1.52(dd,J=13.2,6.7Hz,4H),1.38(dd,J=18.1,13.7Hz,18H),1.32–1.20(m ,32H),1.14(dd,J=11.4,4.5Hz,9H),1.11–1.01(m,16H),0.86(dd,J=8.3,6.8Hz,48H).

[0620] Example 1.53 Synthesis of Compound 53

[0621] Compound 53 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.36 (d, J = 7.4Hz, 3H), 4.67 (d, J = 7.2Hz, 3H), 4.29 (dd, J = 15.6, 6.4Hz, 9H),2.74(d,J=3.4Hz,6H),2.60(s,6H),2.52–2.35(m,12H),2.00(d,J=6.0Hz,6H),1.70(d, J=9.2Hz,10H),1.51(dt,J=19.8,6.6Hz,6H),1.37(ddd,J=15.7,11.6,4.4Hz,16H),1.30–1. 20(m,26H),1.18–1.11(m,8H),1.07(ddd,J=14.9,11.5,5.9Hz,12H),0.86(t,J=7.6Hz,36H).

[0622] Example 1.54 Synthesis of Compound 54

[0623] Compound 54 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.36 (s, 2H), 4.81 (d, J = 7.4Hz, 2H), 4.66 (t, J = 6.1Hz, 4H), 4.35–4.24 (m, 6H), 2. 77(dd,J=13.7,7.4Hz,3H),2.72–2.51(m,3H),2.43(t,J=6.7Hz,3H),2.14–1.96(m,10H),1.77(s,3H) ,1.70(d,J=7.4Hz,12H),1.64–1.57(m,6H),1.57–1.46(m,4H),1.45–1.32(m,8H),1.31–1.17(m,18H) ,1.13(dd,J=11.6,4.5Hz,4H),1.09–1.00(m,6H),0.92(d,J=6.4Hz,2H),0.85(dd,J=8.5,6.6Hz,18H).

[0624] Example 1.55 Synthesis of Compound 55

[0625] Compound 55 was prepared by the method described in Example 1.1. 1H NMR (400MHz, CDCl3) δ5.37(t,J=7.1Hz,4H),4.67(d,J=7.2Hz,8H),4.31(dd,J=13.5,5.1Hz,16H),2.75(t,J=6.9Hz,8H),2.59–2.21 (m,22H),2.00(t,J=6.5Hz,8H),1.71(s,16H),1.63–1.48(m,8H),1.22(dddd,J=38.6,30.2,19.0,12.2Hz,80H),0.90–0.82(m,48H).

[0626] Example 1.56 Synthesis of Compound 56

[0627] Compound 56 was prepared by the method described in Example 1.1. 1 H NMR (400MHz, CDCl3) δ5.36(t,J=6.8Hz,2H),4.67(d,J=7.2Hz,3H),4.34–4.27(m,6H),2.83(dd,J=13.6,6.9Hz,2H),2.63(dd,J= 13.8,7.4Hz,6H),2.52–2.41(m,6H),2.22–1.78(m,9H),1.70(d,J=8.4Hz,8H),1.60–0.97(m,42H),0.85(dd,J=8.5,6.7Hz,24H).

[0628] Example 1.57

[0629] Preparation of nanoparticle compositions

[0630] The 56 cationic lipid compounds prepared in Example 1.1-56 were dissolved in anhydrous ethanol with a molar ratio of 66.67:25.67:6.67:1.00 with cholesterol (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.), DSPC alcohol (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.) and DMG-PEG2000 (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.). Lipid nanoparticles (LNPs) were prepared with a weight ratio of about 10:1 cationic lipid to firefly luciferase (Fluc) mRNA. In short, mRNA was diluted in 25mM sodium acetate solution (pH 5.2), and the ethanolic solution of lipids was mixed with the mRNA aqueous solution at a ratio of about 1:3 (volume / volume) using a syringe pump, with a total flow rate of 12mL / min. The LNP was replaced into ddH2O by removing ethanol by dialysis. Finally, the lipid nanoparticles were filtered through a sterile filter with a 0.2μm pore to obtain an LNP preparation (LNP-mFluc) encapsulating firefly luciferase mRNA.

[0631] Example 1.58

[0632] In vivo evaluation of luciferase mRNA using lipid nanoparticle compositions

[0633] The lipid nanoparticle composition (LNP-mFluc) prepared in Example 1.57 was separately evaluated in vivo for luciferase mRNA. FLuc mRNA from Shanghai Hexincheng Biotechnology expresses the luciferase protein, originally isolated from fireflies. Fluc is commonly used in mammalian cell culture to measure gene expression and cell viability. It emits bioluminescence in the presence of the substrate luciferin. Studies were conducted in 5-6 week old female Balb / c mice (Shanghai Slake Laboratory Animal Co., Ltd.) according to the guidelines established by the Committee on Animal Care (ACC) and the Canadian Council on Animal Care (CCAC). A mixture containing 5 μg of luciferase mRNA and 50 μg of cationic lipid nanoparticles was injected via the tail vein. Six hours after administration, 100 μL of 30 mg / mL D-luciferin potassium salt (Adamas Reagents Co., Ltd.) was intraperitoneally injected into the mice. Ten minutes later, the mice were imaged using an in vivo imaging system (PerkinElmer). Compounds with strong fluorescence intensity in the liver and their specific fluorescence values ​​are shown in Table 2. Compound 9, compound 32, compound 21, compound 8, compound 10, compound 33, compound 16, compound 30, compound 15, compound 2, compound 51, compound 56, compound 26, compound 25, compound 29, compound 5, compound 42, compound 53, compound 52, compound 13, and compound 50 have strong fluorescence signals in the spleen, and the fluorescence intensity is basically above about 1.17E+07, especially compound 50, the fluorescence intensity of which can reach as high as 1.03E+08. Compound 17, which has a strong signal in the lungs, has a fluorescence signal intensity of approximately 6.95E+05.

[0634] Table 2 Fluorescence intensity in the liver

[0635] Example 2

[0636] Example 2.1: In vitro screening of LNPs for macrophage transfection (method establishment)

[0637] In order to obtain LNPs for in vitro transfection of macrophages, an in vitro screening method was first established (Figure 1). The specific steps are as follows: Step 1: LNPs from the LNP library were encapsulated with luc-mRNA and transfected into the RAW264.7 macrophage cell line for preliminary screening. The cells were lysed and detected by a microplate reader, and the Luc fluorescence intensity represented the transfection efficiency. Step 2: LNPs with higher transfection efficiency in the cell line were selected, and LNPs were encapsulated with EGFP-mRNA and transfected into primary macrophages derived from mouse bone marrow (BMDM) for further fine screening. The proportion of EGFP-positive cells was detected by flow cytometry to represent the transfection efficiency. Finally, the target LNPs for in vitro transfection of primary macrophages were obtained.

[0638] Example 2.2: Preparation of LNP

[0639] 1. Prepare 2.5μl, 20μl, 200μl, and 1000μl pipettes, 10, 200, and 1000μl sterile nuclease-free pipette tips, 1.5ml centrifuge tubes, 15ml centrifuge tubes, DEPC water, sodium acetate buffer (pH = 5.2), 75% alcohol, anhydrous ethanol, 1.5ml centrifuge tube rack, and 15 / 50ml centrifuge tube rack (all the liquids and tubes mentioned above are sterile and nuclease-free).

[0640] 2. Prepare the working solutions of cholesterol (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.), DSPC alcohol (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.), cationic lipids, and DMG-PEG2000 (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.) in advance with anhydrous ethanol. The concentration of the working solutions is 10 mg / ml. Seal and store in the refrigerator to prevent ethanol volatilization from affecting the concentration.

[0641] 3. According to the mass ratio of cationic lipids (No. 1-42, No. 44-56), cholesterol, DSPC, and DMG-PEG 2000 of 50:19.25:5:0.75; the mass ratio of cationic lipid (No. 43), cholesterol, DSPC, and DMG-PEG 2000 of 50:35.77:9.29:1.39, take the cationic lipids, cholesterol, DSPC, and DMG-PEG and mix them in a 1.5 ml centrifuge tube, add a certain volume of anhydrous ethanol to prepare a final concentration of 5 mg / ml mix, vortex for 1 min to mix, sonicate for 1 min, and continue vortexing for 1 min; separately, take 3 times the volume of 25 mM sodium acetate solution (pH 5.2) and uniformly drip the mix into the vortexed sodium acetate buffer to obtain LNP.

[0642] Example 2.3: Preparation of LNP-mRNA Complex 1

[0643] The LNP prepared in Example 2.2 was placed in a dialysis bag (3.5K, Thermo Scientific) and dialyzed with ultrapure water at room temperature for more than 3 hours. The dialyzed LNP concentration was between 0.8 and 1 μg / μl. The LNP:RNA (w / w) ratio was 10:1 and incubated for 15 minutes. The mixture was concentrated in a 15 ml 50 kDa ultrafiltration centrifuge tube at 5000 g, and the complex 1 was injected intratumorally at a volume of 30-50 μl / mouse.

[0644] Example 2.4: Preparation of LNP-mRNA Complex 2

[0645] The LNP prepared in Example 2.2 was placed in a dialysis bag (3.5K, Thermo Scientific) and dialyzed with ultrapure water at room temperature for more than 3 h. The LNP concentration after dialysis was between 0.8 and 1 μg / ul. The LNP:RNA (w / w) ratio was 10:1 and incubated for 15 min to obtain complex 2 for tail vein injection.

[0646] Example 2.5: Preparation of LNP-mRNA Complex 3

[0647] The LNP prepared in Example 2.2 was mixed with LNP:RNA (w / w) = 10:1 and incubated for 15 min to obtain complex 3 used for cell transfection.

[0648] Example 2.6: Delivery of Luc-mRNA to RAW264.7 cells by LNP-mRNA complexes

[0649] Raw264.7 cells were seeded and cultured in 96-well plates in DMEM high-glucose medium supplemented with 10% FBS, with 2x104 cells per well. Penicillin (100 U / ml) and streptomycin (100 μg / ml) were added to the culture medium. LNP-luc-RNA complex 3 prepared in Example 2.5 was diluted with DMEM medium to an RNA concentration of 0.02 μg / μl. 10 μl (i.e., 0.2 μg RNA) was added to each well and cultured for 20 hours. Cells were lysed using a firefly luciferase reporter gene assay kit (Yeasen, 11404ES60), and fluorescence analysis of the cells was performed on a microplate reader to determine the transfection efficiency of the LNP-RNA complex. The results are shown in Figure 2 (LNPs 1-56 from left to right). Most of the LNPs from LNPs 1-56 were able to transfect RAW264.7 cells. For example, compounds No. 43, No. 38, No. 37, No. 28, No. 27, No. 50, No. 53, No. 23, No. 48, No. 34, No. 29, No. 10, No. 19, No. 52, No. 40, No. 7, No. 42, No. 45, No. 41, No. 25, No. 13, No. 21, No. 56, No. 3, No. 15, No. 4, No. 16, and No. 20 all have good transfection effects.

[0650] Example 2.7: Delivery of EGFP-mRNA to BMDM cells by LNP-mRNA complex

[0651] Prepare forceps, scissors, a 2ml syringe, a 1ml syringe, a 70um cell strainer, a 6cm dish, pre-chilled PBS, red blood cell lysis buffer, and BMM culture medium: DMEM complete medium with 10ng / ml M-CSF; 75% ethanol; and a 6-well plate. Add 75% ethanol to the first well (to disinfect the bones); add approximately 1ml of culture medium to the second and third wells (to rinse the bones); and add 3ml of culture medium to the fourth well (to rinse the bones).

[0652] 2. Kill C57 mice by cervical dislocation and soak in 75% ethanol for 2 minutes to sterilize.

[0653] 2. Cut the skin along the midline of the abdomen to expose the field of vision

[0654] 3. Cut the skin down along the femur, remove the hair, separate the femur and tibia, remove the foot, and gently rub the tissue with a paper towel. This is the best way to remove excess tissue (i.e. muscle and fat) on the bone.

[0655] 4. Transfer the separated femur and tibia to the first well of a six-well plate and soak the bones in 75% (well / volume) ethanol for 1 minute. (Do not place broken bones in ethanol)

[0656] 5. Place them into the second well filled with 1 mL of BMM medium.

[0657] 6. Move them to the third well filled with 1 mL of BMM medium.

[0658] 7. Use a 1ml syringe needle inserted into a 2ml syringe to collect 2ml of fresh BMM medium.

[0659] 8. Remove the tibia from the culture dish and cut it at an angle at the ankle joint.

[0660] 9. Collect bone marrow. a. Hold the tibia over a 6-cm dish with the narrow end of the tibia pointing downward. b. Insert the needle into the top of the bone marrow and eject the culture medium. c. Collect 2 mL of BMM culture medium in the 6-cm dish and insert it again. Continue flushing several times. When the bone is white, discard it.

[0661] 10. Add 12 ml of culture medium to the 6 cm dish and blow gently to mix well.

[0662] 11. Plate 2 ml of the cell suspension per well in a 6-well plate and record it as Day 0.

[0663] 12. Obtain mature BMDM on Day 7.

[0664] 13. Aspirate the supernatant of the BMM culture medium in the six-well plate, wash twice with PBS, and replace with DMEM complete culture medium.

[0665] 14. Select LNP No. 27, 28, 37, 38, 43, and 50 and prepare LNP-EGFP-RNA complexes according to the method of Example 2.5. Dilute the RNA to a concentration of 0.02 μg / μl using DMEM medium, add 100 μl (i.e., 2 μg RNA) to each well, and culture for 20 hours. Detect F480 by flow cytometry (FACS). + CD11b + EGFP + The percentage of cells is the transfection efficiency of the LNP-RNA complex, and the results are shown in Figures 3-1 and 3-2. LNP No. 43 had the highest transfection efficiency.

[0666] Example 2.8: LNP-mRNA complex delivery of CAR-CD19 / HER2-mRNA to BMDM cells

[0667] 1. Obtain mature BMDM cells according to the method of Example 2.7 (steps 1-13).

[0668] 2. Select LNP No. 43 to prepare LNP-CAR-CD19 / HER2-RNA complex according to the method of Example 2.5, dilute with DMEM medium to an RNA concentration of 0.02ug / ul, add 100ul (i.e. 2ug RNA) to each well, and culture for 20 hours. Detect F480 by flow cytometry (FACS). + CD11b + CAR-HER2 + The cell percentage, i.e., the transfection efficiency of the LNP-mRNA complex, was generated by FlowJo analysis software, and the results are shown in Figure 4. The transfection efficiency of LNP No. 43 in BMDM cells was approximately 14%, which directly demonstrated the successful expression of CAR mRNA and the successful construction of CAR-BMDM cells.

[0669] Example 2.9: LNP polarizes M0-Raw264.7 cells to M1

[0670] Raw264.7 cells were seeded and cultured in 6-well plates in DMEM high-glucose medium (HyClone, SH30022.01B) supplemented with 10% FBS, containing penicillin (100 U / ml) and streptomycin (100 μg / ml), with 1×10 6 cells per well. The LNP No. 43 with higher transfection efficiency in Example 2.6 (the ratio of cationic lipid No. 43, cholesterol, DSPC, and DMG-PEG 2000 is 50:35.77:9.29:1.39) and the LNP with lower transfection efficiency (called 43-1, the ratio of cationic lipid No. 43, cholesterol, DSPC, and DMG-PEG 2000 is 50:38.5:10:1.5) were prepared according to the method of Example 2.5. The LNP-EGFP-RNA complex was diluted with DMEM culture medium to an RNA concentration of 0.02 μg / ul and 0.03 μg / ul, and 100 μl (i.e., 2 μg RNA, 20 μg LNP and 3 μg RNA, 30 μg LNP) was added to each well. LNP without RNA encapsulation was added as a control, and cultured for 20 hours; the supernatant was discarded, the cells were washed twice with PBS, the cells were scraped with a cell scraper, and F480 was detected by flow cytometry (FACS). + CD11b +The MFI of cellular iNOS-APC, as shown in Figure 5-1 (EGFP-Count flow cytometry histogram) and Figure 5-2 (iNOS-Count flow cytometry histogram, generated by FlowJo analysis software), demonstrate that LNPs not only deliver mRNA but also promote macrophage polarization from M0 to M1. The fact that empty LNPs can also induce polarization suggests that M1 polarization is primarily driven by LNPs, not RNA. The fact that LNP #43 of the same mass can induce polarization, while LNP #43-1 (Figure 5-1), with a lower transfection efficiency, does not (Figure 5-1), suggests that M1 polarization requires LNPs with a high transfection efficiency. Furthermore, LNP #43 only induces polarization at a certain dose, indicating that a certain dose of LNP is required for M1 polarization.

[0671] Example 2.10: LNP polarizes M0-BMDM cells to M1

[0672] 1. Obtain mature BMDM cells according to the method of Example 2.7 (steps 1-13).

[0673] 2. Select LNP No. 27, 28, 37, 38, 43, and 50 to prepare LNP-EGFP-RNA complexes according to the method of Example 2.5, dilute with DMEM medium to an RNA concentration of 0.02 μg / μl, add 100 μl (i.e., 2 μg RNA) to each well, and culture for 20 hours. Detect F480 by flow cytometry (FACS). + CD11b + The MFI of cellular iNOS-APC is the polarization effect of different LNPs. The results are shown in Figure 6-1 (flow cytometry scatter plot, generated by Flowjo analysis software) and Figure 6-2. The polarization effect is better in BMDM, among which LNPs 37 and 38 are the best.

[0674] Example 2.11: LNP polarizes M2-BMDM cells to M0 type

[0675] 1. Obtain mature BMDM cells according to the method of Example 2.7 (steps 1-13).

[0676] 2. Add 20 ng / mL IL-4 to DMEM complete medium to prepare M2 macrophage culture medium.

[0677] 3. Cultivate mature BMDM cells in M2 culture medium for 48 hours to obtain M2 BMDM

[0678] 4. Select LNP No. 43 and LNP No. 37 to prepare LNP-EGFP-mRNA complexes according to the method of Example 2.5, dilute the RNA concentration to 0.02 μg / μl with DMEM medium, add 100 μl (i.e., 2 μg RNA) to each well of mature BMDM in a 6-well plate, and culture for 20 hours to obtain EGFP-BMDM.

[0679] 5. Scrape the EGFP-BMDM from one well of the six-well plate with a scraper and add them to the M2 BMDM in one well of the six-well plate and culture them for 48 hours.

[0680] 6. Detect F480 by flow cytometry (FACS) + CD11b + The proportion of M2 type in cells is shown in Figure 7 (flow cytometry, produced by flowjo flow cytometry analysis software). Both LNP No. 43 and No. 37 converted M2 type macrophages into M0 type.

[0681] Example 2.12: Raji cell killing experiment

[0682] 1. Obtain mature BMDM cells according to the method of Example 2.7 (steps 1-13).

[0683] 2. The LNP No. 43 obtained in Example 2.7 was used to prepare the LNP-CAR CD19-mRNA complex according to the method of Example 2.5, diluted to an RNA concentration of 0.02ug / ul with DMEM medium, 100ul (i.e., 2ug RNA) was added to each well, and cultured for 20 hours to obtain CAR CD19-BMDM.

[0684] 3. Add luc to the six-well plate according to the E / T ratio of 20:1, 10:1, 1:1, 1:10, and 1:20. + Raji cells, the final volume of each well was 1 ml. The positive control consisted of Raji cells alone without CAR-BMDM cells, and the volume was made up to 1 ml with culture medium. The negative control was BMDM cells co-incubated with Raji cells. After 24 hours, the supernatant was taken and the cells were lysed using a firefly luciferase reporter gene assay kit (yeasen, 11404ES60). The fluorescence analysis of Raji cells was performed using a microplate reader. The killing ratio was calculated as follows: (positive control fluorescence intensity - experimental group fluorescence intensity) / (positive control fluorescence intensity - background fluorescence intensity) × 100%. The results are shown in Figure 8-1 and Figure 8-2 of the in vivo model. CAR CD19-BMDM can kill Raji cells.

[0685] Example 2.13: HER2 + MC38 cell killing experiment

[0686] 1. Obtain mature BMDM cells according to the method of Example 2.7 (steps 1-13).

[0687] 2. The LNP No. 43 obtained in Example 2.7 was used to prepare LNP-CAR HER2-mRNA complex according to the method of Example 2.5. The RNA concentration was diluted to 0.02 μg / μl with DMEM medium. 100 μl (i.e., 2 μg RNA) was added to each well and cultured for 20 hours to obtain CAR HER2-BMDM. The BMDM was scraped with a scraper and plated in a 96-well plate with 3*10 cells per well. 4 cells (i.e. 3*10 3 CAR-BMDM), plated overnight;

[0688] 3. Add luc to the 96-well plate according to the E / T ratio of 20:1, 10:1, 5:1, 2.5:1, 1:2, 1:10, and 1:20. + HER2 + MC38 cells, the final volume per well is 100ul, the positive control is luc only + HER2 + MC38 cells were cultured without CAR-BMDM cells, and the volume was made up to 100ul with culture medium. The negative control was BMDM cells co-incubated with Raji cells. After 24 hours, all cells in the 96-well plate were lysed using a firefly luciferase reporter gene assay kit (yeasen, 11404ES60). The fluorescence analysis of the cells was performed on a microplate reader. The killing ratio was calculated as follows: (negative control fluorescence intensity - experimental group fluorescence intensity) / (negative control fluorescence intensity - background fluorescence intensity) × 100%. The results are shown in Figure 9. CAR HER2-BMDM can kill HER2 + MC38 cells.

[0689] Example 2.14: CAR-BMDM phagocytosis experiment

[0690] 1. Obtain mature BMDM cells according to the method of Example 2.7 (steps 1-13).

[0691] 2. LNP No. 43 obtained in Example 2.7 was used to prepare LNP-CAR HER2-mRNA and LNP-CAR CD19-mRNA complexes according to the method of Example 2.5. The RNA concentration was diluted to 0.02 μg / μl with DMEM medium, 100 μl (i.e., 2 μg RNA) was added to each well, and cultured for 20 hours to obtain CAR HER2-BMDM and CAR CD19-BMDM;

[0692] 3. Add EGFP to the 6-well plate at an E / T ratio of 1:3. +HER2 + MC38 cells, EGFP + HER2 + CT26 cells, the final volume of each well was 1 ml, negative controls were CAR CD19-BMDM cells and BMDM cells with luc + HER2 + MC38 cells, luc + HER2 + CT26 cells were co-incubated and F480 was detected by flow cytometry (FACS) 4 hours later. + CD11b + Cell EGFP + The ratio is the specific phagocytic ratio of CAR HER2-BMDM, and the results are shown in Figure 10. The proportion of cells undergoing phagocytosis in BMDM is about 10%.

[0693] Example 2.15: In vivo targeting of LNP in wild-type Balb / C mice

[0694] LNPs No. 27, 28, 37, 43, and 50 were selected to prepare LNP-CAR HER2-luc-mRNA complexes according to the method of Example 2.4. 20ug mRNA / mouse was injected into the tail vein. After 6 hours, the bioluminescence intensity distribution in the mouse body was measured by the IVIS small animal in vivo imaging system, as well as the bioluminescence intensity distribution of the heart, liver, spleen, lung, kidney, and bone marrow after dissection. Before imaging, the mouse was intraperitoneally injected with 100 μL of D-luciferin potassium salt (30 mg / mL, dissolved in PBS). As shown in Figures 11-1, 11-2, and 11-3, LNP No. 37 was mainly distributed in the spleen and liver, and there was also a signal in the bone marrow. The fluorescence signal intensity of the remaining LNPs was lower than that of No. 37.

[0695] Example 2.16: LNP targeting in C57 mice bearing wild-type MC38 tumor cells

[0696] LNPs 27, 28, 37, 38, and 43 were selected to prepare LNP-CAR HER2-luc-mRNA complexes according to the method of Example 2.3. 5 μg mRNA / mouse was injected intratumorally, and the bioluminescence intensity distribution in mice was measured using an IVIS small animal in vivo imaging system at 6 h, 24 h, and 48 h, respectively. Before imaging, mice were intraperitoneally injected with 100 μL of D-luciferin potassium salt (30 mg / mL, dissolved in PBS). As shown in Figures 12-1 and 12-2, LNP 37 had the highest expression and best stability in the tumor.

[0697] Example 2.17: Targeting of LNP in Cre transgenic reporter mice

[0698] LNP No. 37 was selected to prepare LNP-Cre-mRNA complex according to the method of Example 2.4. 10 μg and 20 μg mRNA / mouse were injected into the tail vein respectively. After 48 h, Td tomato expression in spleen and bone marrow cells was detected by flow cytometry (FACS). + The cell ratio refers to the type of immune cells in the body that LNP No. 37 is delivered to. As shown in Figures 13-1 and 13-2, LNP No. 37 can transfect a variety of immune cells in the spleen and bone marrow.

[0699] Example 2.18: In vivo construction and validation of in situ CAR-myeloid by LNP-mRNA delivery system

[0700] LNP No. 37 was selected and LNP-HER2-mRNA complex was prepared according to the method of Example 2.4. 20 μg mRNA / mouse was injected into the tail vein. After 24 hours, orbital blood, bone marrow and spleen were collected and CAR-HER2 was detected by flow cytometry (FACS). + Immune cell distribution. The results are shown in Figure 14. LNP No. 37 can generate CAR-immune cells in situ and circulate through the blood to reach various parts of the body.

[0701] Example 2.19: Orthotopic CAR-immune cell therapy for lung metastasis model

[0702] 1. Inject luc cells that overexpress HER2 antigen through the tail vein + CT26 tumor cells were used to establish a lung metastasis model to evaluate the in vivo anti-tumor effect of orthotopic CAR-immune cells. Model mice were randomly divided into two groups of five mice in each group. The bioluminescence intensity of the mouse lungs was measured using the IVIS Small Animal In vivo Imaging System, which indirectly indicates the severity of the tumor. Before imaging, the mice were injected intraperitoneally with 100 μL of D-luciferin potassium salt (30 mg / mL, dissolved in PBS).

[0703] 2. The weight of the mice was measured every two days, and the weight change curves of the two groups of mice were drawn as shown in Figure 15. The weight of the mice in the treatment group was significantly higher than that in the control group. LNP No. 37 was selected to prepare the LNP-HER2-mRNA complex according to the method of Example 2.4, and 20ug mRNA / mouse was injected into the tail vein. The drug was administered once every 4 days for a total of 6 times. The growth of the tumor was monitored by bioluminescence imaging of the tumor, as shown in Figure 16. The results of semi-quantitative fluorescence analysis of mouse lung tumors showed that on the 17th day of treatment, the fluorescence intensity of the lungs of mice treated with LNP-CAR mRNA was significantly weaker than that of the control group, as shown in Figure 17, demonstrating its good tumor inhibitory effect. There were also significant differences in the survival curves of the mice in the treatment group and the control group, as shown in Figure 18, which also proves that the therapy has a good therapeutic effect.

[0704] Example 2.20: In situ CAR-immune cell therapy for solid tumors

[0705] 1. A solid tumor model was constructed by subcutaneously inoculating CT26 tumor cells overexpressing the HER2 antigen to evaluate the anti-solid tumor efficacy of in situ CAR-immune cells. Model mice were randomly divided into an experimental group and a control group, with 9 mice in each group.

[0706] 2. The weight and tumor size of mice were measured every two days, and the weight change curves (as shown in Figure 19) and tumor size change curves (as shown in Figure 20) of the two groups of mice were plotted. The length (L) and width (W) of the tumor were measured using a vernier caliper. The tumor size was calculated using the formula: 1 / 2 × L × W 2 .

[0707] 3. LNP No. 37 was selected and LNP-HER2-mRNA complexes were prepared according to the method of Example 2.4. 20 μg mRNA / mouse was injected into the tail vein, and the drug was administered once every 4 days for a total of 5 doses. On the 10th day of treatment, two mice treated with LNP-CAR mRNA had tumor regression. On the 13th day of treatment, the weight difference between the two groups was significant (as shown in Figure 20), demonstrating the good therapeutic effect of this therapy.

[0708] 4. From the perspective of mouse body weight, long-term administration did not cause weight loss; AST detection also proved that LNP did not cause liver damage (as shown in Figure 21).

[0709] 5. Immunohistochemistry results showed that the Ki67 expression in the experimental group was significantly lower than that in the control group, indicating that the proliferation ability of tumor cells decreased, while the proportion of CD3 and macrophages (F480) increased significantly, indicating that CAR-immune cell immunotherapy was effective (as shown in Figure 22).

[0710] Example 2.21: Immune cell typing for in situ CAR-immune cell therapy in solid tumors

[0711] 1. Randomly select 4 mice from each of the experimental and control groups in Example 2.20, and remove the tumors;

[0712] 2. Place the tumor to be minced in a 1.5ml EP tube, add 200ul tissue lysis buffer (Rayward), and mince with scissors until there is almost no obstruction when using a 1ml pipette;

[0713] 3. After chopping, add 2ml, transfer to the grinding machine tube with a Pasteur tube, add 1ml tissue lysis buffer, and grind using a tissue grinding machine.

[0714] 4. After grinding, filter through a 0.45 μm filter membrane, transfer to a 15 ml centrifuge tube, and centrifuge at 400 g for 5 minutes; discard the supernatant, add 6 ml of lysis buffer, and lyse on ice for 5 minutes; then centrifuge at 400 g for 5 minutes and discard the supernatant;

[0715] 6. Add 6 ml of DMEM to resuspend, centrifuge at 400 g for 5 min, discard the supernatant, and resuspend in DMEM to obtain a single cell suspension;

[0716] 7. The effect of LNP 37 treatment on the reprogramming of the tumor immune microenvironment was detected by flow cytometry. According to the results of flow cytometry analysis, the infiltration of M2 macrophages (CD206+) in the treatment group was reduced (Figure 23). This result proves that the pro-tumor macrophages in the tumor microenvironment have undergone phenotypic shift. In the CD4+T cell flow cytometry analysis, we found that the infiltration of Tfh cells and Th1 in the tumor microenvironment of the treatment group increased (Figure 24). In the CD8+T cell flow cytometry analysis, the percentage of proliferating CD8+T cells (Ki67+) and perforin T cells also increased significantly (Figure 25). In summary, the therapeutic strategy of delivering CAR mRNA in situ to generate CAR-immune cells by LNP 37 increased and enhanced the activity of cytotoxic T cells and changed the tumor immune microenvironment.

[0717] Example 2.22: LNP delivery of circular RNA in vivo

[0718] 1. Place LNP No. 43 prepared according to Example 2.2 in a dialysis bag (3.5K, Thermo Scientific) and dialyze against ultrapure water at room temperature for at least 3 hours; the post-dialysis LNP concentration is between 0.8 and 1 μg / μl. Mix the LNP with circular luc RNA LNP at a mass ratio of 10:1 and incubate for 15 minutes. Concentrate the mixture at 5000g in a 15ml 50kDa ultrafiltration centrifuge tube to obtain the complex for intratumoral injection at a volume of 30-50 μl / mouse.

[0719] 2. 5 μg of the complex mRNA / mouse was injected intratumorally. The bioluminescence intensity distribution in the mice was measured using an IVIS small animal in vivo imaging system at 24, 48, and 72 hours. Prior to imaging, the mice were intraperitoneally injected with 100 μL of D-luciferin potassium salt (30 mg / mL, dissolved in PBS). The results, as shown in Figure 26, demonstrate that LNP No. 43 can also deliver circular RNA.

[0720] Although the embodiments of the present application are described above, the present application is not limited to the above-mentioned specific embodiments and application fields. The above-mentioned specific embodiments are merely illustrative and instructive, and not restrictive. A person of ordinary skill in the art, under the guidance of this specification and without departing from the scope of protection of the claims of this application, can also make many forms, all of which fall within the scope of protection of this application.

Claims

1. A compound of formula (I): or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein: The G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group; The L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) x -, -SS-, -C(=O)S-, -SC(=O)-, -NR a C(=O)-, -C(=O)NR b -、-NR a C(=O)NR b -、-OC(=O)NR b -、-NR a C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R a and R b are each independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl; x is 0, 1, or 2; G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene group; The L3 and L4 are each independently a bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -、-NR c C(=O)NR d -、-OC(=O)NR c -、-NR c C(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR c )O-, -(C6-C10 arylene)-, or -(6- to 10-membered heteroarylene)-; R c and R d are each independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl; i is 0, 1, or 2; Said G5 and G6 are each independently an optionally substituted C2-C24 straight chain alkyl group or an optionally substituted C2-C24 straight chain alkenyl group; The Z is an optionally substituted C1-C12 alkylene, an optionally substituted -R e G7R f -; Among them, R e and R f is an optionally substituted C1-C12 alkylene group; G7-NR g -, -(3-7 membered saturated cycloalkane)-, -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-; R g is an optionally substituted C1-C12 alkylene group; Said X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G1L1G3L3G5, or X and Z together with the nitrogen to which they are attached form a ring.

2. The compound according to claim 1, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that The compound has the structure shown in formula (IA): wherein G1, G2, G3, G4, G5, G6, L1, L2, L3, L4, X and Y are as defined in claim 1; G8 is an optionally substituted C1-C12 alkylene group.

3. The compound according to claim 1, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that The compound has the structure shown in formula (IB): Among them, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e 、R f , X and Y are as defined in claim 1.

4. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that wherein G1 and G2 are unsubstituted C2-C4 alkylene.

5. The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that wherein L1 and L2 are -C(=O)O-.

6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that Among them, G3 and G4 are bonds.

7. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that wherein G3 and G4 are unsubstituted C2-C4 alkylene groups.

8. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that Wherein L3 and L4 are bonds.

9. The compound according to any one of claims 1 to 5 and 7, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: wherein L3 and L4 are -OC(=O)O-.

10. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.

11. The compound according to any one of claims 2, 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IA-1): Wherein, m is 1 or 3, n is 0 or 1, G5 and G6 are defined as defined in claim 10, G8 is defined in claim 2, G9 and G 10 is an optionally substituted C1-C5 straight-chain alkane.

12. The compound according to any one of claims 2, 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IA-2): wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are as defined in claim 10.

13. The compound according to any one of claims 2, 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IA-3): wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are as defined in claim 10.

14. The compound according to any one of claims 2, 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IA-4): wherein G1, G2, G3, G4, G5, G6, L1, L2, L3, L4 and Y are as defined in claim 1; and G8 is an optionally substituted C1-C12 alkylene group.

15. The compound according to any one of claims 2, 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein the compound has the structure represented by formula (IA-5): in, m is 1 or 3, n is 0 or 1, Y, G5 and G6 are as defined in claim 1; and G8 is an optionally substituted C1-C12 alkylene group.

16. The use according to any one of claims 2, 4-10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein the compound has the structure represented by formula (IA-6): in, m is 1 or 3, n is 0 or 1, and Y, G5 and G6 are as defined in claim 1.

17. The compound according to any one of claims 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IB-1): wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are as defined in claim 10.

18. The compound according to any one of claims 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IB-2): wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are as defined in claim 10.

19. The compound according to any one of claims 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: The compound has a structure shown in formula (IB-3): wherein m is 1 or 3, n is 0 or 1, and G5 and G6 are as defined in claim 10.

20. The use according to any one of claims 3 to 10, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein the compound has a structure represented by formula (IB-4): in, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e and R f As defined in claim 1.

21. The compound according to any one of claims 2, 4-11, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: wherein G8 is an optionally substituted C2-C4 alkylene group.

22. The compound according to any one of claims 2, 4-11, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, characterized in that: Among them G9 or G 10 Or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl.

23. A compound according to any one of claims 1 to 22, wherein G5 or G6 or both have one of the following structures:

24. The compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, which is:

25. A composition comprising: a therapeutic agent or a prophylactic agent; and a carrier for delivering the therapeutic agent or the prophylactic agent, wherein The carrier comprises a cationic lipid, and the cationic lipid comprises one or more of the compound represented by formula (I) according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof.

26. The composition of claim 25, wherein the therapeutic agent or preventive agent is selected from one or more of a nucleic acid molecule, a small molecule compound, a polypeptide or a protein, preferably, wherein the nucleic acid molecule is selected from one or more of single-stranded DNA, double-stranded DNA, a short isomer, agomir, antagomir, antisense molecule, small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicersubstrate RNA (dsRNA), small hairpin RNA (shRNA), transfer RNA (tRNA), messenger RNA (mRNA), locked nucleic acid (LNA), peptide nucleic acid (PNA) or morpholino oligonucleotide.

27. The composition of claim 26, wherein the therapeutic or prophylactic agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof. Preferably, the mRNA is a monocistronic mRNA or a polycistronic mRNA.

28. The composition according to claim 27, wherein the antigen is a pathogenic antigen.

29. The composition of claim 26, wherein the mRNA comprises one or more functional nucleotide analogs selected from one or more of pseudouridine, 1-methyl-pseudouridine, or 5-methylcytosine.

30. According to claim 25, the small molecule compound is selected from one or more of antitumor drugs, anti-infective drugs, local anesthetics, antidepressants, anticonvulsants, antibiotics / antibacterial agents, antifungals, antiparasitic drugs, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, anti-glaucoma agents, anesthetics or imaging agents. The composition according to claim 25 , wherein the mass ratio of the carrier to the therapeutic or preventive agent is 5:1 to 50:

1.

32. The composition according to claim 25, wherein the composition is a nanoparticle preparation, wherein the average size of the nanoparticle preparation is 10 to 500 nm; or wherein the pKa of the nanoparticles is 4.5 to 8.

5.

33. A composition according to any one of claims 25 to 32, wherein The carrier further comprises one or more neutral lipids.

34. The composition according to claim 33, wherein the neutral lipid is one or more selected from phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, ceramide, sterol and derivatives thereof.

35. The composition according to any one of claims 25 to 34, wherein the molar ratio of cationic lipid to neutral lipid is 100:1 to 5:

1.

36. according to the composition described in any one of claim 25 to 32, it further comprises steroid, preferably, described steroid is selected from cholesterol, non-sterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatine, tomatine, ursolic acid, alpha-tocopherol, one or more in corticosteroid.

37. The composition of any one of claims 25 to 36, wherein the molar ratio of cationic lipid to steroid is 2:1 to 4:

1.

38. The composition according to any one of claims 25 to 36, wherein the composition further comprises one or more lipids capable of binding to a polymer, preferably, the lipid capable of binding to a polymer is one or more selected from PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol or PEG-modified dialkylglycerol, further preferably, the molar ratio of the cationic lipid to the lipid capable of binding to a polymer is 100:1 to 20:

1.

39. The composition according to any one of claims 25 to 36, wherein the carrier further comprises a neutral lipid, a structural lipid and a polymer-conjugated lipid, and the molar ratio of the cationic lipid, the neutral lipid, the steroid lipid and the polymer-conjugated lipid is (15-70):(1-15):(15-55):(0-3).

40. The composition according to claim 25, characterized in that The composition further comprises a pharmaceutically acceptable excipient. Preferably, the excipient comprises a pharmaceutically acceptable diluent.

41. Use of a compound of formula (I) as described in any one of claims 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition as described in any one of claims 25 to 40 in the preparation of a drug, wherein the drug is preferably any one selected from a gene drug, a nucleic acid vaccine, a small molecule drug, a polypeptide or a protein drug.

42. Use of a compound of formula (I) according to any one of claims 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition according to any one of claims 25 to 40 in targeting immune cells.

43. Use of a compound of formula (I) according to any one of claims 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition according to any one of claims 25 to 40 in the preparation of a drug targeting immune cells.

44. The use according to claim 42 or 43, wherein The immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.

45. Use of a compound of formula (I) according to any one of claims 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition according to any one of claims 25 to 40 in promoting cell polarization.

46. Use of a compound of formula (I) according to any one of claims 1 to 24, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, or a composition according to any one of claims 25 to 40 in the preparation of a medicament for promoting immune cell polarization.

47. The use according to claim 45 or 46, wherein The cell polarization is from M0 type to M1 type polarization.

48. The use according to claim 45 or 46, wherein The cell polarization is from M2 type to M0 type.

49. The use according to claim 45 or 46, wherein The cells are macrophages.

50. A method for screening lipid nanoparticles in vitro, comprising: The first screening was conducted in macrophage cell lines to obtain lipid nanoparticles that can transfect macrophage cell lines; Among the obtained lipid nanoparticles, those with a FLuc fluorescence signal intensity higher than 10,000 RLUs were selected for a second screening in bone marrow-derived primary macrophages; The target lipid nanoparticles were obtained after the second screening.

51. The method of claim 50, wherein: The macrophage cell line is the Raw264.7 cell line.

52. A method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising: Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene are injected into wild-type mice via the tail vein, and the first lipid nanoparticles expressing CAR-mRNA in a given organ are screened and obtained with an expression ratio higher than 80%. Optionally, the first lipid nanoparticles obtained by screening are encapsulated with CAR-mRNA carrying a reporter gene and injected intratumorally into tumor-bearing mice to screen for a second lipid nanoparticle that is expressed only in the tumor site and not in other organs and is stably expressed for 24 to 48 hours; The first or second lipid nanoparticles obtained by screening were injected into Cre reporter gene mice through the tail vein to screen for Td tomato in immune cells. + Cell-targeted lipid nanoparticles.

53. The method of claim 50, wherein: The given organ is selected from the spleen or bone marrow.

54. The method of claim 50, wherein: The immune cells are selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes and mast cells.

55. The method according to any one of claims 50 to 54, wherein The target lipid nanoparticles are prepared from the compound of formula (I) involved in claims 1-24 or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof.

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