Immune cell targeted lipid nanoparticles as well as screening method and application thereof
By screening lipid nanoparticles in vitro and in vivo using the LNP-mRNA delivery system, the problem of tumor microenvironment isolation in the treatment of solid tumors with immunocellular therapy was solved, achieving efficient construction and stable expression of CAR-immune cells and enhancing tumor killing ability.
Patent Information
- Application Number
- CN202410757306.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-06-12
- Publication Date
- 2025-12-12
AI Technical Summary
Existing immunotherapy methods for treating solid tumors suffer from problems such as tumor microenvironment isolation and immunosuppression, making it difficult for immune cells to infiltrate and kill. Traditional methods for editing cells are inefficient and time-consuming.
Through in vitro macrophage screening and in vivo screening of LNP-mRNA delivery systems, lipid nanoparticles capable of constructing various CAR-immune cells in situ at tumor sites were screened, achieving targeted delivery and polarization of immune cells.
It simplifies the cell editing process, improves the anti-tumor effect of immune cells at the tumor site, achieves efficient CAR-immune cell construction and stable expression, promotes the polarization of M1 and M2 macrophages, and enhances tumor killing ability.
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Figure CN121108003A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of biomedical technology, and more specifically, to LNP-mRNA delivery systems, mRNA, and their uses. Background Technology
[0002] Immunotherapy includes CAR-T, CAR-NK, CAR-DC, and CAR-Macrophage, among others. Many immunotherapy methods, especially CAR-T therapy, have achieved great success in the treatment of hematological malignancies. However, single-cell immunotherapy still has limitations in the treatment of solid tumors. This is because the tumor microenvironment is often isolated within dense fibrous masses, making it difficult for immune cells to infiltrate and exert their killing effect. Simultaneously, the immunosuppressive microenvironment easily leads to cell depletion. Traditional methods of in vitro formation of CAR-immune cells followed by reinfusion often suffer from low cell editing efficiency and long construction times. The current challenge lies in how to form multiple CAR-immune cells in vivo, stimulate an immune response at the tumor site, and enhance the anti-tumor effect produced by a single CAR-immune cell. Summary of the Invention
[0003] 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 for LNPs (lipid nanoparticles) that can form a variety of CAR-immune cells in vivo, this application first screens macrophages in vitro and then further screens them in vivo to obtain LNPs that can be constructed in situ to form a variety of CAR-immune cells.
[0004] Specifically, this application adopts the following technical solution:
[0005] 1. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in targeting immune cells,
[0006]
[0007] in:
[0008] G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups;
[0009] 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 arylene)-;
[0010] R a and R b Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0011] x is 0, 1, or 2;
[0012] G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups;
[0013] 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 heteroarylene)-;
[0014] R c and R d Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0015] i is 0, 1, or 2;
[0016] G5 and G6 are each independently a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group;
[0017] Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -;
[0018] Among them, R e and Rf Optionally substituted C1-C12 alkylene groups;
[0019] G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-;
[0020] R g Optionally substituted C1-C12 alkylene groups;
[0021] X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
[0022] 2. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in the preparation of a medicament targeting immune cells.
[0023]
[0024] in:
[0025] G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups;
[0026] 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 heteroarylene)-;
[0027] R a and R b Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0028] x is 0, 1, or 2;
[0029] G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups;
[0030] 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 heteroarylene)-;
[0031] R c and R d Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0032] i is 0, 1, or 2;
[0033] G5 and G6 are each independently a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group;
[0034] Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -;
[0035] Among them, R e and R f Optionally substituted C1-C12 alkylene groups;
[0036] G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-;
[0037] R g Optionally substituted C1-C12 alkylene groups;
[0038] X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
[0039] 3. The use according to item 1 or 2, wherein the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
[0040] 4. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in promoting cell polarization.
[0041]
[0042] in:
[0043] G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups;
[0044] 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 heteroarylene)-;
[0045] R a and R b Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0046] x is 0, 1, or 2;
[0047] G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups;
[0048] 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 heteroarylene)-;
[0049] R c and R d Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0050] i is 0, 1, or 2;
[0051] G5 and G6 are each independently a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group;
[0052] Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -;
[0053] Among them, R e and R f Optionally substituted C1-C12 alkylene groups;
[0054] G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-;
[0055] R g Optionally substituted C1-C12 alkylene groups;
[0056] X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
[0057] 5. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in the preparation of a drug that promotes immune cell polarization.
[0058]
[0059] in:
[0060] G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups;
[0061] 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 heteroarylene)-;
[0062] R a and R b Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0063] x is 0, 1, or 2;
[0064] G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups;
[0065] 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 heteroarylene)-;
[0066] R c and R d Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0067] i is 0, 1, or 2;
[0068] G5 and G6 are each independently a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group;
[0069] Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -;
[0070] Among them, R e and R f Optionally substituted C1-C12 alkylene groups;
[0071] G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-;
[0072] R g Optionally substituted C1-C12 alkylene groups;
[0073] X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
[0074] 6. The use according to item 4 or 5, wherein the cell polarization is from M0 type to M1 type polarization.
[0075] 7. The use according to item 4 or 5, wherein the cell polarization is from M2 type to M0 type polarization.
[0076] 8. The use according to item 4 or 5, wherein the cell is a macrophage.
[0077] 9. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA):
[0078]
[0079] Among them, G1, G2, G3, G4, G5, G6, L1, L2, L3, L4, X and Y are as defined in item 1;
[0080] G8 is an optionally substituted C1-C12 alkylene group.
[0081] 10. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB):
[0082]
[0083] Among them, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e Rf X and Y are as defined in item 1.
[0084] 11. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G1 and G2 are unsubstituted C2-C4 alkylene groups.
[0085] 12. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein L1 and L2 are -C(=O)O-.
[0086] 13. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G3 and G4 are bonds.
[0087] 14. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G3 and G4 are unsubstituted C2-C4 alkylene groups.
[0088] 15. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein L3 and L4 are bonds.
[0089] 16. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein L3 and L4 are -OC(=O)O-.
[0090] 17. For the use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
[0091] 18. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-1):
[0092]
[0093] Where m is 1 or 3, n is 0 or 1, G5 and G6 are defined as in items 1-8, G8 is defined as in item 2, and G9 and G... 10 It is a C1-C5 straight-chain alkane that is optionally substituted.
[0094] 19. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-2):
[0095]
[0096] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in items 1-8.
[0097] 20. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-3):
[0098]
[0099] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in items 1-8.
[0100] 21. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-4):
[0101]
[0102] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in items 1-8.
[0103] 22. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB-1):
[0104]
[0105] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in item 10.
[0106] 23. The compound having the structure shown in formula (IB-2) according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof:
[0107]
[0108] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in items 1-8.
[0109] 24. The use according to any one of items 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB-3):
[0110]
[0111] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in items 1-8.
[0112] 25. The use according to item 18, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G8 is optionally a substituted C2-C4 alkylene group.
[0113] 26. The use as described in item 18, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G9 or G 10 Or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl.
[0114] 27. The use according to any one of items 18-24, wherein G5 or G6 or both have one of the following structures:
[0115]
[0116] 28. The use according to any one of items 1-27, wherein the compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof is prepared as a composition for use, preferably,
[0117] The composition further comprises a therapeutic or preventative agent and a carrier for delivering the therapeutic or preventative agent, the carrier comprising a cationic lipid comprising one or more of the compounds represented by formula (I) or pharmaceutically available salts thereof.
[0118] 29. A method for in vitro screening of lipid nanoparticles, comprising:
[0119] The first screening was conducted in macrophage cell lines to obtain lipid nanoparticles that can be transfected into macrophage cell lines;
[0120] Lipid nanoparticles with FLuc fluorescence signal intensity higher than 10,000 RLUs were selected from the obtained lipid nanoparticles and subjected to a second screening in primary macrophages derived from bone marrow.
[0121] The target lipid nanoparticles were obtained after the second screening.
[0122] 30. The method according to item 29, wherein the macrophage cell line is the Raw264.7 cell line.
[0123] 31. A method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising:
[0124] Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene were injected into wild-type mice via the tail vein, and the first lipid nanoparticles that were expressed in a given organ and had an expression rate of more than 80% were screened.
[0125] Optionally, the first lipid nanoparticles encapsulating CAR-mRNA carrying the reporter gene were screened and injected intratumorally into tumor-bearing mice. The second lipid nanoparticles were screened and expressed only at the tumor site, not in other organs, and stably expressed for 24–48 h.
[0126] The first or second lipid nanoparticles obtained through screening were injected via the tail vein into Cre reporter mice, and mice with Td tomato-like immune cells were screened for. + Target lipid nanoparticles for cells.
[0127] 32. The method according to item 29, wherein the given organ is selected from the spleen or bone marrow.
[0128] 33. The method according to item 29, wherein the immune cells are selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
[0129] 34. The method according to any one of items 29-33, wherein the target lipid nanoparticles are prepared from a compound of formula (I) involved in items 1-28 or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof.
[0130] Invention Effects
[0131] The beneficial effects of this invention are:
[0132] 1. The LNP screening method for in vitro macrophage mRNA delivery provided in this application solves the problems of high primary cell usage and long primary cell extraction time caused by direct screening in primary macrophages.
[0133] 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-immunotherapy.
[0134] 3. The LNP-mRNA complex provided in this application can deliver mRNA to macrophages with short transfection time, simple transfection method, and a transfection rate of 30.2%, providing a reference for cell editing methods in adoptive immunotherapy.
[0135] 4. The LNP-mRNA complex provided in this application can deliver circular mRNA and can be stably expressed for 72 hours.
[0136] 5. Some LNPs provided in this application can polarize unpolarized M0 macrophages into M1 pro-inflammatory phenotypes.
[0137] 6. Some LNPs provided in this application can polarize anti-inflammatory and pro-tumor M2 macrophages into M0 type.
[0138] 7. Some LNPs provided in this application can deliver mRNA to the spleen and bone marrow to generate various CAR-immune cells, including T cells, macrophages, DC cells, and NK cells.
[0139] 8. The in vivo in situ CAR-cells provided in this application have shown good therapeutic effects in lung metastasis and solid tumor models.
[0140] 9. The LNP preparation method provided in this application is simple, reproducible, and the delivered mRNA can be stably expressed in vivo for 48 hours, showing good application prospects. Attached Figure Description
[0141] The accompanying drawings are provided to better understand this application and do not constitute an undue limitation thereof. Wherein:
[0142] Figure 1 This is the screening flowchart in Example 1;
[0143] Figure 2 This is a graph showing the screening results of LNPs on Raw264.7 cells in Example 6;
[0144] Figure 3-1 This is a graph showing the screening results of LNPs by flow cytometry on BMDM cells in Example 7.
[0145] Figure 3-2 This is a graph showing the screening and transfection efficiency results of LNPs on BMDM cells in Example 7;
[0146] Figure 4 This is a diagram showing the results of transfecting CAR-HER2 mRNA onto LNP 43 in BMDM cells in Example 8;
[0147] Figure 5-1 The results show the effects of different transfection efficiencies of LNPs (43, 43-1) on macrophage polarization in Raw264.7 cells in Example 9, as well as the effects of RNA with different mass encapsulation on macrophage polarization (represented by fluorescence).
[0148] Figure 5-2 The results are LNPs (43, 43-1) with different transfection efficiencies on Raw264.7 cells in Example 9, and the effect of RNA with different mass encapsulation on macrophage polarization (represented by iNOS).
[0149] Figure 6-1 This refers to the polarization effect of different LNPs on BMDM cells in Example 10;
[0150] Figure 6-2 This is the polarization effect of different LNPs on BMDM cells in Example 10 (statistical results);
[0151] Figure 7In Example 11, LNPs 37 and 43 polarized M2-BMDM cells into the M0 type;
[0152] Figure 8-1 This is a graph showing the killing effect (killing ratio) of CAR CD19-BMDM cells on Raji cells in Example 12;
[0153] Figure 8-2 This is a graph showing the results of CAR CD19-BMDM cells killing Raji cells in Example 12 (detected by fluorescence analysis);
[0154] Figure 9 The CAR HER2-BMDM cells in Example 13 kill HER2 + Results image of MC38 cells;
[0155] Figure 10 This refers to the CAR HER2-BMDM cells phagocytosis of HER2 in Example 14. + MC38 cells and HER2 + CT26 cell results image;
[0156] Figure 11-1 This describes the biodistribution of several LNPs in wild-type B / C mice (in vivo) as shown in Example 15.
[0157] Figure 11-2 This shows the biodistribution of several LNPs in wild-type B / C mice in Example 15 (after dissection);
[0158] Figure 11-3 This is a statistical chart showing the biodistribution of several LNPs in wild-type B / C mice in Example 15.
[0159] Figure 12-1 The changes in signal intensity over time of various LNPs in wild-type MC38 tumor cell-bearing C57 mice (in vivo) as described in Example 16;
[0160] Figure 12-2 The changes in signal intensity over time of various LNPs in wild-type MC38 tumor cell-bearing C57 mice, as shown in Example 16.
[0161] Figure 13-1 This refers to the specific detection results of bone marrow immune cells in Cre transgenic reporter mice in Example 17;
[0162] Figure 13-2 This refers to the specific detection results of spleen immune cells in Cre transgenic reporter mice in Example 17;
[0163] Figure 14 HER2 in peripheral blood in Example 18 + Cell distribution;
[0164] Figure 15 These are the body weight change curves of mice in the control group (UT) and the treatment group (Treated) in Example 19;
[0165] Figure 16 These are IVIS imaging results of mice in the control group (UT) and treatment group (Treated) in Example 19;
[0166] Figure 17 This is a quantitative graph of the lung fluorescence signal detected by IVIS in mice of the control group (UT) and the treatment group (Treated) in Example 19;
[0167] Figure 18 This is a survival curve graph of mice in the control group (UT) and the treatment group (Treated) in Example 19;
[0168] Figure 19 These are the body weight change curves of mice in the control group (UT) and the treatment group (Treated) in Example 20;
[0169] Figure 20 These are the tumor size change curves of mice in the control group (UT) and treatment group (Treated) in Example 20;
[0170] Figure 21 This is a graph showing the AST and ALT test results of mice in the control group (UT) and treatment group (Treated) in Example 20;
[0171] Figure 22 This is the immunohistochemical analysis of tumors in the control group (UT) and treatment group (Treated) mice in Example 21.
[0172] Figure 23 This is a flow cytometry analysis of M2 macrophages in tumor sites of mice in the control group (UT) and treatment group (Treated) in Example 21.
[0173] Figure 24 This is a flow cytometry analysis of CD4+ cells in the tumor sites of mice in the control group (UT) and treatment group (Treated) in Example 21.
[0174] Figure 25 This is a flow cytometry analysis of CD8+ cells in the tumor sites of mice in the control group (UT) and treatment group (Treated) in Example 21.
[0175] Figure 26 These are IVIS imaging results of tumor sites at 24h, 48h, and 72h after LNP delivery of circular Luc mRNA in Example 22. Detailed Implementation
[0176] The following description provides exemplary embodiments of this application, including various details to aid understanding, and should be considered merely exemplary. Therefore, those skilled in the art will recognize that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of this application. Similarly, for clarity and brevity, descriptions of well-known functions and structures are omitted in the following description.
[0177] This application provides for the use of compounds of formula (I) or pharmaceutically acceptable salts, prodrugs, or stereoisomers thereof in targeted immune cells.
[0178]
[0179] in:
[0180] G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups;
[0181] 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 heteroarylene)-;
[0182] R a and R b Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0183] x is 0, 1, or 2;
[0184] G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups;
[0185] 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)-, -NRc 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 heteroarylene)-;
[0186] R c and R d Each is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl;
[0187] i is 0, 1, or 2;
[0188] G5 and G6 are each independently a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group;
[0189] Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -;
[0190] Among them, R e and R f Optionally substituted C1-C12 alkylene groups;
[0191] G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-;
[0192] R g Optionally substituted C1-C12 alkylene groups;
[0193] X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
[0194] This application further provides the use of compounds of formula (I) above, or pharmaceutically acceptable salts, prodrugs or stereoisomers thereof, in the preparation of medicaments targeting immune cells.
[0195] In one specific embodiment of the above-described uses, the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
[0196] This application further provides the use of compounds of formula (I) above, or pharmaceutically acceptable salts, prodrugs or stereoisomers thereof, in promoting cell polarization.
[0197] This application further provides the use of the compound of formula (I) above, or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, in the preparation of a medicament that promotes immune cell polarization.
[0198] In one specific embodiment of the use in promoting cell polarization or in the preparation of a drug that promotes the polarization of immune cells, the cell polarization is a polarization from M0 type to M1 type.
[0199] In one specific embodiment of the use in promoting cell polarization or in the preparation of a drug that promotes the polarization of immune cells, the cell polarization is a polarization from M2 type to M0 type.
[0200] In one specific embodiment of the use in promoting cell polarization or in the preparation of drugs that promote immune cell polarization, the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells. Macrophages are preferred.
[0201] In any of the uses described above, the structure of the compound of formula (I) is as follows:
[0202] Preferably, G1 and G2 are unsubstituted C2-C4 alkylene groups, 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g The C1-C12 alkylene groups are optionally substituted; the C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X and Z are cyclic with the nitrogen to which they are attached, and each of X and Y is independently and optionally substituted.
[0203] Preferably, L1 and L2 are -C(=O)O-, and G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups. 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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g X and Y are optionally substituted C1-C12 alkylene groups; each of X and Y is independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z cyclic with the nitrogen to which they are attached.
[0204] Preferably, G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups, and G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R bEach of the following is independently H, optionally substituted C1-C12 alkyl, or optionally substituted C1-C12 alkenyl; x is 0, 1, or 2; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g X and Y are optionally substituted C1-C12 alkylene groups; each of X and Y is independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z cyclic with the nitrogen to which they are attached.
[0205] Preferably, L3 and L4 are bonds or -OC(=O)O-, and G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each of the following 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 bonded, optionally substituted C2-C24 straight-chain alkylene; G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g X and Y are optionally substituted C1-C12 alkylene groups; each of X and Y is independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z cyclic with the nitrogen to which they are attached.
[0206] Preferably, L3 and L4 are bonds, and G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R bEach of the following 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 bonded, optionally substituted C2-C24 straight-chain alkylene; G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g X and Y are optionally substituted C1-C12 alkylene groups; each of X and Y is independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z cyclic with the nitrogen to which they are attached.
[0207] Preferably, G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups, and G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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; Z is optionally substituted C1-C12 alkylene, optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g X and Y are optionally substituted C1-C12 alkylene groups; each of X and Y is independently an optionally substituted C1-C12 straight-chain alkyl group, -G1L1G3L3G5, or X and Z cyclic with the nitrogen to which they are attached.
[0208] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group; G1 and G2 are each independently a 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 bO-, -(C6-C10 arylene)- or -(6 to 10 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g It is an optionally substituted C1-C12 alkylene group.
[0209] In one specific embodiment, X and Y are each independently -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 aC(=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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g It is an optionally substituted C1-C12 alkylene group.
[0210] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, and 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f-; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g It is an optionally substituted C1-C12 alkylene group.
[0211] In one specific embodiment, X is -G1L1G3L3G5, and Y is 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 cO-, -(C6-C10 arylene)- or -(6 to 10 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; Z is optionally substituted C1-C12 alkylene or optionally substituted -R e G7R f -; where R e and R f G7 is an optionally substituted C1-C12 alkylene group; G7 is -NR g - (3-7 membered saturated cycloalkane), - (3-7 membered heterocyclic alkane)-, - (3-7 membered cyclic arylene)- or - (3-7 membered cyclic heteroarylene)-; R g It is an optionally substituted C1-C12 alkylene group.
[0212] In one specific embodiment, Z is a C2-C4 alkylene group, and G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -S(O) i -, -SS-, -C(=O)S-, -SC(=O)-, -NR cC(=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 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 substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; X and Y are each independently substituted C1-C12 straight-chain alkyl, -G1L1G3L3G5, or X and Z cyclized with the nitrogen to which they are attached.
[0213] In one specific implementation, Z is optionally replaced by -R e G7R f -, R e and R f G7 is an optionally substituted C2-C4 alkylene group, and G1 and G2 are each optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R bEach 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl; X and Y are each independently substituted C1-C12 straight-chain alkyl, -G1L1G3L3G5, or X and Z cyclized with the nitrogen to which they are attached.
[0214] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; Ra and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0215] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently 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 heteroarylene)-; R a and R bEach 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0216] In one 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-, or -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 heteroarylene)-; R a and R bEach 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0217] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, or -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 heteroarylene)-; R a and R bEach 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0218] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is an optionally substituted C2-C4 alkylene group, and G1 and G2 are each optionally substituted C2-C24 straight-chain alkylene groups; 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 bO-, -(C6-C10 arylene)- or -(6 to 10 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0219] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is an optionally substituted C2-C4 alkylene group, and G1 and G2 are each optionally substituted C2-C24 straight-chain alkylene groups; 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 aC(=O)O-, -SC(=S)-, -C(=S)S-, -C(=S)-, -CH(OH)-, -P(=O)(OR b O-, -(C6-C10 arylene)- or -(6 to 10 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0220] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is an optionally substituted C2-C4 alkylene group, and G1 and G2 are each optionally substituted C2-C24 straight-chain alkylene groups; 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 -、-NRa 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0221] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is an optionally substituted C2-C4 alkylene group, and G1 and G2 are each optionally substituted C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0222] In one specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0223] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0224] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently -C(=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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0225] In one 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 bonded, optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0226] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded, optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0227] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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)NRd -、-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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0228] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0229] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0230] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0231] In one specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; 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 bonded, optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0232] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; 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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0233] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently -C(=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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0234] In one 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 bonded, optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0235] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded, optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0236] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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)NRd -、-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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0237] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0238] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0239] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0240] In one specific embodiment, X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; 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 bonded, optionally substituted C2-C24 straight-chain alkylene group; L3 and L4 are each independently a bonded, -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 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 optionally substituted C2-C24 straight-chain alkyl or optionally substituted C2-C24 straight-chain alkenyl.
[0241] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0242] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups, optionally substituted C2-C24 straight-chain alkenyl groups.
[0243] In one 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, 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, optionally substituted C2-C24 straight-chain alkenyl group.
[0244] In one specific embodiment, X is -G1L1G3L3G5, Y is 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, 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, optionally substituted C2-C24 straight-chain alkenyl group.
[0245] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and Rf G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0246] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0247] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0248] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0249] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkyl, optionally substituted C2-C24 straight-chain alkenyl.
[0250] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0251] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -C(=O)O-; G3 and G4 are each independently -C2-C24 straight-chain alkylene groups, optionally substituted; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently -C2-C24 straight-chain alkyl groups, optionally substituted C2-C24 straight-chain alkenyl groups.
[0252] In one 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0253] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0254] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0255] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0256] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0257] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0258] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently independently C2-C24 straight-chain alkylene with optional substituted structure; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently C2-C24 straight-chain alkyl and optionally substituted C2-C24 straight-chain alkenyl.
[0259] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0260] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -C(=O)O-; G3 and G4 are each independently -C2-C24 straight-chain alkylene groups, optionally substituted; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently -C2-C24 straight-chain alkyl groups, optionally substituted C2-C24 straight-chain alkenyl groups.
[0261] In one 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0262] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0263] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0264] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0265] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0266] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0267] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently independently C2-C24 straight-chain alkylene with optional substituted structure; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently C2-C24 straight-chain alkyl and optionally substituted C2-C24 straight-chain alkenyl.
[0268] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0269] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups, optionally substituted C2-C24 straight-chain alkenyl groups.
[0270] In one 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, 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, optionally substituted C2-C24 straight-chain alkenyl group.
[0271] In one specific embodiment, X is -G1L1G3L3G5, Y is 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, 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, optionally substituted C2-C24 straight-chain alkenyl group.
[0272] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0273] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0274] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0275] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0276] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkyl, optionally substituted C2-C24 straight-chain alkenyl.
[0277] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups and optionally substituted C2-C24 straight-chain alkenyl groups.
[0278] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently substituted C2-C24 straight-chain alkyl groups, optionally substituted C2-C24 straight-chain alkenyl groups.
[0279] In one 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, 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, optionally substituted C2-C24 straight-chain alkenyl group.
[0280] In one specific embodiment, X is -G1L1G3L3G5, Y is 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, 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, optionally substituted C2-C24 straight-chain alkenyl group.
[0281] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0282] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0283] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0284] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkylene and optionally substituted C2-C24 straight-chain alkenyl.
[0285] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C2-C24 straight-chain alkyl, optionally substituted C2-C24 straight-chain alkenyl.
[0286] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0287] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -C(=O)O-; G3 and G4 are each independently -C2-C24 straight-chain alkylene groups, optionally substituted; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently -C4-C16 straight-chain alkenyl groups, optionally substituted.
[0288] In one 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0289] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently C4-C16 straight-chain alkenyl groups.
[0290] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0291] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R.e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0292] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0293] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0294] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently optionally substituted C4-C16 straight-chain alkenyl.
[0295] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0296] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -C(=O)O-; G3 and G4 are each independently -C2-C24 straight-chain alkylene groups, optionally substituted; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently -C4-C16 straight-chain alkenyl groups, optionally substituted.
[0297] In one 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0298] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently C4-C16 straight-chain alkenyl groups.
[0299] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0300] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0301] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0302] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0303] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently optionally substituted C4-C16 straight-chain alkenyl.
[0304] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0305] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0306] In one 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0307] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0308] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0309] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, Re and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0310] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0311] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0312] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently independently optionally substituted C4-C16 straight-chain alkenyl.
[0313] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0314] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0315] In one 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0316] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded and optionally substituted C2-C24 straight-chain alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0317] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0318] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0319] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0320] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 straight-chain alkylene; G1 and G2 are each independently optional substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded and optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 straight-chain alkenyl.
[0321] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl, Z is C2-C4 alkylene, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded, optionally substituted C2-C24 straight-chain alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently independently optionally substituted C4-C16 straight-chain alkenyl.
[0322] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0323] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently -optionally substituted C4-C16 straight-chain alkenyl groups.
[0324] In one 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 bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0325] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0326] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0327] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R eand R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0328] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0329] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0330] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently independently C2-C24 straight-chain alkylene groups that are optionally substituted; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently C4-C16 straight-chain alkenyl groups that are optionally substituted.
[0331] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0332] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently -optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently -optionally substituted C4-C16 straight-chain alkenyl groups.
[0333] In one 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 bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0334] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0335] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0336] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0337] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0338] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0339] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently independently C2-C24 straight-chain alkylene groups that are optionally substituted; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently independently C4-C16 straight-chain alkenyl groups that are optionally substituted.
[0340] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0341] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0342] In one 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0343] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0344] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0345] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0346] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0347] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0348] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently independently C2-C24 straight-chain alkylene groups that are optionally substituted; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently C4-C16 straight-chain alkenyl groups that are optionally substituted.
[0349] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and optionally substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0350] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently independently substituted C2-C24 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently independently substituted C4-C16 straight-chain alkenyl groups.
[0351] In one 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0352] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0353] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; and G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0354] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R fG7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0355] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0356] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7-membered heterocyclic alkylene)-, which is optionally substituted C2-C24 linear alkylene; G1 and G2 are each independently optional substituted C2-C24 linear alkylene; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 linear alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optional substituted C4-C16 linear alkenyl.
[0357] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently independently C2-C24 straight-chain alkylene groups that are optionally substituted; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; G5 and G6 are each independently independently C4-C16 straight-chain alkenyl groups that are optionally substituted.
[0358] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently and -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently and -OC(=O)O-; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0359] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0360] In one 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 unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently optional substituted C4-C16 straight-chain alkenyl groups.
[0361] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0362] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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.
[0363] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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.
[0364] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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.
[0365] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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 one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0367] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently and -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently and -OC(=O)O-; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0368] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0369] In one 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 unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently independently optional substituted C4-C16 straight-chain alkenyl groups.
[0370] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0371] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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.
[0372] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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.
[0373] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R fG7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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.
[0374] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded 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 one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently -OC(=O)O-; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0376] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0377] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0378] In one 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 unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0379] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0380] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0381] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R fG7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0382] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0383] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0384] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0385] In one specific embodiment, X and Y are each independently and optionally substituted C1-C3 straight-chain alkyl groups, and Z is a C2-C4 alkylene group; G1 and G2 are each independently and unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently and optionally substituted C4-C16 straight-chain alkenyl groups.
[0386] In one specific embodiment, X and Y are each independently -G1L1G3L3G5, and Z is a C2-C4 alkylene group; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0387] In one 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 unsubstituted C2-C4 straight-chain alkylene group; L1 and L2 are each independently -C(=O)O-; G3 and G4 are bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0388] In one specific embodiment, X is -G1L1G3L3G5, Y is 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 bonds or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonds; and G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
[0389] In one specific embodiment, X and Y are each independently a optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0390] In one specific implementation, X and Y are each independently -G1L1G3L3G5, and Z is optionally replaced by -R. e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0391] In one specific embodiment, X is an optionally substituted C1-C3 straight-chain alkyl group, Y is -G1L1G3L3G5, and Z is an optionally substituted -R e G7R f -, R e and R f G7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0392] In one specific embodiment, X is -G1L1G3L3G5, Y is an optionally substituted C1-C3 straight-chain alkyl group, and Z is an optionally substituted -R group. e G7R f -, R e and R fG7 is a -(3-7 membered heterocyclic alkylene)-, which is optionally substituted 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 bonded or unsubstituted C2-C4 alkylene; L3 and L4 are each independently bonded; G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
[0393] In one specific embodiment, X and Y are each independently C1-C3 straight-chain alkyl groups, Z is a C2-C4 alkylene group, and X and Z are cyclic with the nitrogen they are attached to; G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are either bonded or unsubstituted C2-C4 alkylene groups; L3 and L4 are each independently bonded; and G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl groups.
[0394] In one specific embodiment, the compound has the structure shown in formula (IA):
[0395]
[0396] Wherein, G1, G2, G3, G4, G5, G6, L1, L2, L3, L4, X and Y are as defined in claim 1;
[0397] G8 is an optionally substituted C1-C12 alkylene group.
[0398] In one specific embodiment, the compound has the structure shown in formula (IB):
[0399]
[0400] 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.
[0401] In one embodiment of the structure shown in a specific formula (IB), G1 and G2 are unsubstituted C2-C4 alkylene groups.
[0402] In one embodiment of the structure shown in the specific formula (IB), L1 and L2 are -C(=O)O-.
[0403] In one embodiment of the structure shown in Formula (IB), G3 and G4 are bonds.
[0404] In one embodiment of the structure shown in a specific formula (IB), G3 and G4 are unsubstituted C2-C4 alkylene groups.
[0405] In one embodiment of the structure shown in Formula (IB), L3 and L4 are bonds.
[0406] In one embodiment of the structure shown in the specific formula (IB), L3 and L4 are -OC (=O)O-.
[0407] In one embodiment of the structure shown in a specific formula (IB), G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
[0408] In one specific embodiment, the compound has the structure shown in formula (IA-1):
[0409]
[0410] Where m is 1 or 3, n is 0 or 1, G5 and G6 are defined as in claims 1-8, G8 is defined as in claim 2, and G9 and G... 10 It is a C1-C5 straight-chain alkane that is optionally substituted.
[0411] In one specific embodiment, the compound has the structure shown in formula (IA-2):
[0412]
[0413] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
[0414] In one specific embodiment, the compound has the structure shown in formula (IA-3):
[0415]
[0416] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
[0417] In one specific embodiment, the compound has the structure shown in formula (IA-4):
[0418]
[0419] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
[0420] In one specific embodiment, the compound has the structure shown in formula (IB-1):
[0421]
[0422] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in claim 10.
[0423] In one specific embodiment, the compound has the structure shown in formula (IB-2):
[0424]
[0425] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
[0426] In one specific embodiment, the compound has the structure shown in formula (IB-3):
[0427]
[0428] Where m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
[0429] In one embodiment of the structure shown in formula (IB-3), G8 is an optionally substituted C2-C4 alkylene group.
[0430] In one specific embodiment of the structure shown in formula (IB-3), wherein G9 or G 10 Or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl.
[0431] In one embodiment of the structure shown in formula (IB-3), G5 or G6 or both have one of the following structures:
[0432]
[0433] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2-chain linear alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C4 linear alkylene groups; L3 and L4 are each independently and optionally -OC(=O)O-; G5 and G6 are each independently and optionally substituted C2-C24 linear alkenyl groups; Z is an optionally substituted C2-C4 alkylene group or optionally substituted -R e G7R f -; where R e and R fG1 is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocyclic alkylene)-; X and Y are each independently an optionally substituted C1-C12 straight-chain alkylene, -G1L1G3L3G5 or X, Z cyclic with the nitrogen to which they are attached.
[0434] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2-chain linear alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C4 linear alkylene groups; L3 and L4 are each independently and optionally -OC(=O)O-; G5 and G6 are each independently and optionally substituted C2-C24 linear alkenyl groups; Z is an optionally substituted C2-C4 alkylene group or optionally substituted -R e G7R f -; where R e and R f G1 is an optionally substituted C1-C4 alkylene; G7 is -(3-7-membered heterocyclic alkylene)-; X and Y are each independently an optionally substituted C1-C4 straight-chain alkylene or -G1L1G3L3G5.
[0435] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded or optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently bonded or -OC(=O)O-; G5 and G6 are each independently and optionally substituted C2-C24 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0436] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C2-C24 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0437] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C2-C24 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0438] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C2-C24 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently hydroxyl- or amino-substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0439] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C2-C24 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is a C1-C4 straight-chain alkyl group; and Y is a hydroxyl-substituted C1-C4 straight-chain alkyl group.
[0440] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C2-C24 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is G1L1G3L3G5; and Y is an amino-substituted C1-C4 straight-chain alkyl group.
[0441] In one specific embodiment, G1 and G2 are each independently a 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 an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C2-C4 alkylene group; and X and Y are each independently a C1-C4 straight-chain alkyl group.
[0442] In one specific embodiment, G1 and G2 are each independently a 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 an optionally substituted C2-C24 straight-chain alkenyl group; Z is an optionally substituted C2-C4 alkylene group; and X and Y are each independently G1L1G3L3G5.
[0443] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently and optionally -OC(=O)O-; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group or optionally substituted -R e G7R f -; where R e and R f G1 is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocyclic alkylene)-; X and Y are each independently an optionally substituted C1-C12 straight-chain alkylene, -G1L1G3L3G5 or X, Z cyclic with the nitrogen to which they are attached.
[0444] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently and optionally -OC(=O)O-; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group or optionally substituted -R e G7R f -; where R e and R fG1 is an optionally substituted C1-C4 alkylene; G7 is -(3-7-membered heterocyclic alkylene)-; X and Y are each independently an optionally substituted C1-C4 straight-chain alkylene or -G1L1G3L3G5.
[0445] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded or optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently bonded or -OC(=O)O-; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0446] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0447] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0448] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently hydroxyl- or amino-substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0449] In one specific embodiment, G1 and G2 are each independently a 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 an optionally substituted C12-C16 straight-chain alkenyl group; Z is an optionally substituted C2-C4 alkylene group; X is a C1-C4 straight-chain alkyl group; and Y is a hydroxyl-substituted C1-C4 straight-chain alkyl group.
[0450] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently and optionally substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is G1L1G3L3G5; and Y is an amino-substituted C1-C4 straight-chain alkyl group.
[0451] In one specific embodiment, G1 and G2 are each independently a 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 an optionally substituted C12-C16 straight-chain alkenyl group; Z is an optionally substituted C2-C4 alkylene group; and X and Y are each independently a C1-C4 straight-chain alkyl group.
[0452] In one specific embodiment, G1 and G2 are each independently a 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 an optionally substituted C12-C16 straight-chain alkenyl group; Z is an optionally substituted C2-C4 alkylene group; and X and Y are each independently G1L1G3L3G5.
[0453] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently and optionally -OC(=O)O-; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group or optionally substituted -R e G7R f -; where Re and R f G1 is an optionally substituted C1-C4 alkylene; G7 is -(3-7 membered heterocyclic alkylene)-; X and Y are each independently an optionally substituted C1-C12 straight-chain alkylene, -G1L1G3L3G5 or X, Z cyclic with the nitrogen to which they are attached.
[0454] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently and optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently and optionally -OC(=O)O-; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group or optionally substituted -R e G7R f -; where R e and R f G1 is an optionally substituted C1-C4 alkylene; G7 is -(3-7-membered heterocyclic alkylene)-; X and Y are each independently an optionally substituted C1-C4 straight-chain alkylene or -G1L1G3L3G5.
[0455] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded or optionally substituted C2-C4 straight-chain alkylene groups; L3 and L4 are each independently bonded or -OC(=O)O-; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently independently substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0456] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0457] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently and optionally substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0458] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently hydroxyl- or amino-substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0459] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is a C1-C4 straight-chain alkyl group; and Y is a hydroxyl-substituted C1-C4 straight-chain alkyl group.
[0460] In one specific embodiment, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is G1L1G3L3G5; and Y is an amino-substituted C1-C4 straight-chain alkyl group.
[0461] In one specific embodiment, G1 and G2 are each independently a C2 linear alkylene group that is optionally substituted; 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 C2-C4 alkyl-substituted C12-C16 linear alkenyl group; Z is an optionally substituted C2-C4 alkylene group; and X and Y are each independently a C1-C4 linear alkyl group.
[0462] In one specific embodiment, G1 and G2 are each independently a C2 linear alkylene group that is optionally substituted; 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 C2-C4 alkyl-substituted C12-C16 linear alkenyl group; Z is an optionally substituted C2-C4 alkylene group; and X and Y are each independently G1L1G3L3G5.
[0463] In one specific implementation, when polarized from M0 type to M1 type, the compound of formula (I) is Wherein, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently hydroxyl- or amino-substituted C1-C4 straight-chain alkyl groups or -G1L1G3L3G5, provided that X and Y are not simultaneously C1-C4 straight-chain alkyl groups or -G1L1G3L3G5.
[0464] In one specific implementation, when polarized from M0 type to M1 type, the compound of formula (I) is Wherein, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is a C1-C4 straight-chain alkyl group; and Y is a hydroxyl-substituted C1-C4 straight-chain alkyl group.
[0465] In one specific implementation, when polarized from M2 type to M0 type, the compound of formula (I) is Wherein, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X is G1L1G3L3G5; and Y is an amino-substituted C1-C4 straight-chain alkyl group.
[0466] In one specific implementation, when polarized from M2 type to M0 type, the compound of formula (I) is Wherein, G1 and G2 are each independently and optionally substituted C2 straight-chain alkylene groups; L1 and L2 are each independently -C(=O)O-; G3 and G4 are each independently bonded; L3 and L4 are each independently bonded; G5 and G6 are each independently C2-C4 alkyl-substituted C12-C16 straight-chain alkenyl groups; Z is an optionally substituted C2-C4 alkylene group; X and Y are each independently G1L1G3L3G5.
[0467] This application further provides the following compounds listed in Table 1, or their available salts, prodrugs, or stereoisomers:
[0468] Table 1 Representative Compounds
[0469]
[0470]
[0471]
[0472]
[0473]
[0474]
[0475]
[0476]
[0477] In any of the preceding uses, the compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof is prepared as a composition for use.
[0478] In one specific embodiment, the composition further comprises a therapeutic or preventative agent and a carrier for delivering the therapeutic or preventative agent, the carrier comprising a cationic lipid comprising one or more of the compounds represented by formula (I) or pharmaceutically available salts thereof.
[0479] In the compositions of this application, the therapeutic or preventative agent may be a nucleic acid molecule, a small molecule compound, a polypeptide or a protein, or a mixture of two or more of these.
[0480] In one specific embodiment, the nucleic acid molecule is selected from single-stranded DNA, double-stranded DNA, short isomers, agomir, antagomir, antisense molecules, circular mRNA, 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 morpholine ring oligonucleotides.
[0481] In one specific embodiment, the therapeutic or preventative agent comprises at least one mRNA encoding an antigen or a fragment thereof or an epitope, preferably, the mRNA being a monocistronic mRNA or a polycistronic mRNA.
[0482] In one specific implementation, the antigen is a pathogenic antigen.
[0483] In one specific embodiment, the mRNA comprises one or more functional nucleotide analogs, preferably selected from one or more of pseudouridine, 1-methyl-pseudouridine, or 5-methylcytosine.
[0484] In one specific embodiment, the small molecule compound is selected from one or more of the following: antitumor drugs, anti-infective drugs, local anesthetics, antidepressants, anticonvulsants, antibiotics / antibacterial agents, antifungal drugs, antiparasitic drugs, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, antiglaucoma agents, anesthetics, or imaging agents.
[0485] As described above, the amount of carrier to therapeutic agent or preventive agent in the composition provided in this application is not limited. In one specific embodiment, the mass ratio of the carrier to the therapeutic agent or preventive agent is (1.5:2 to 50:1).
[0486] In one specific embodiment, the composition of this application is a nanoparticle formulation, wherein the average size of the nanoparticle formulation is 10-500 nm.
[0487] In one specific embodiment, the pKa of the nanoparticle formulation of this application is 4.5 to 8.5.
[0488] The composition provided in this application as described above, wherein the carrier further comprises one or more neutral lipids, preferably selected from one or more of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, ceramide, sterols and their derivatives.
[0489] In one specific embodiment, the molar ratio of the cationic lipid to the neutral lipid is about 100:1 to 5:1.
[0490] In one specific embodiment, the steroid is selected from one or more of cholesterol, nonsteroidal, sitosterol, ergosterol, campesterol, stigmasterol, brassosterol, tomatine, ursolic acid, α-tocopherol, and corticosteroids.
[0491] In one specific embodiment, the molar ratio of the cationic lipid to the steroid is between 2:1 and 4:1.
[0492] As described above, the composition provided in this application further comprises one or more lipids capable of binding to a polymer. Preferably, the lipids capable of binding to the polymer are 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.
[0493] In one specific embodiment, the molar ratio of the cationic lipid to the lipid capable of binding to the polymer is about 100:1 to 20:1.
[0494] In one specific embodiment, the carrier in the composition of this application further includes neutral lipids, structural lipids, and polymer conjugated lipids, wherein 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).
[0495] In one specific embodiment, the composition further includes a pharmaceutically acceptable excipient.
[0496] In one specific embodiment, the excipient includes a pharmaceutically acceptable diluent.
[0497] This application further provides a method for in vitro screening of lipid nanoparticles, comprising:
[0498] The first screening was conducted in macrophage cell lines to obtain lipid nanoparticles that can be transfected into macrophage cell lines;
[0499] Lipid nanoparticles with FLuc fluorescence signal intensity higher than 10,000 RLUs were selected from the obtained lipid nanoparticles and subjected to a second screening in primary macrophages derived from bone marrow.
[0500] The target lipid nanoparticles were obtained after the second screening.
[0501] In one specific embodiment, the macrophage cell line is the Raw264.7 cell line.
[0502] In one specific embodiment, the FLuc fluorescence signal intensity above 10000 RLUs can be above 20000 RLUs, 30000 RLUs, 40000 RLUs, 50000 RLUs, 60000 RLUs, 70000 RLUs, 80000 RLUs, 90000 RLUs, 100000 RLUs, 110000 RLUs, 120000 RLUs, 130000 RLUs, 140000 RLUs, 150000 RLUs, 160000 RLUs, 170000 RLUs, 180000 RLUs, 190000 RLUs, 200000 RLUs, or more.
[0503] This application further provides a method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising:
[0504] Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene were injected into wild-type mice via the tail vein, and the first lipid nanoparticles that were expressed in a given organ and had an expression rate of more than 80% were screened.
[0505] Optionally, the first lipid nanoparticles obtained by screening encapsulate CAR-mRNA carrying the reporter gene and inject them intratumorally into tumor-bearing mice. The second lipid nanoparticles are then selected and expressed only at the tumor site, not in other organs, and stably expressed for 24–48 h. The other organs refer to organs without tumors.
[0506] The first or second lipid nanoparticles obtained through screening were injected via the tail vein into Cre reporter mice, and mice with Td tomato-like immune cells were screened for. + Target lipid nanoparticles for cells.
[0507] In one specific implementation, the Td tomato +The higher the number of cells, the better the lipid nanoparticles obtained through screening are suited for in vivo delivery of mRNA to immune cells. However, this application does not impose any restrictions on this; only those with Td tomato... + The cells meet the requirements of the screening method.
[0508] In one specific implementation, the given organ is selected from the spleen or bone marrow.
[0509] In one specific embodiment, the immune cells are selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
[0510] In one specific embodiment, the target lipid nanoparticles as described above are prepared from compounds of formula (I) provided in this application or their pharmaceutically acceptable salts, prodrugs or stereoisomers.
[0511] Example
[0512] Example 1: Method for screening LNP-transfected macrophages in vitro (method establishment)
[0513] To obtain LNPs from macrophages transfected in vitro, an in vitro screening method was first established. Figure 1 The specific steps are as follows: Step 1: Transfect RAW264.7 macrophage cell lines with LNPs from the LNP library wrapped in luc-mRNA for initial screening. Cell lysis is detected by microplate reader, and the transfection efficiency is represented by the intensity of luc fluorescence. Step 2: Select LNPs with high transfection efficiency from the cell lines and transfect them with EGFP-mRNA wrapped in LNPs into mouse bone marrow-derived primary macrophages (BMDM) for further fine screening. The transfection efficiency is represented by the proportion of EGFP-positive cells detected by flow cytometry. Finally, the target LNPs for in vitro transfection of primary macrophages are obtained.
[0514] Example 2: Preparation method of LNP
[0515] 1. Prepare 2.5μl, 20μl, 200μl, and 1000μl pipettes; 10, 200, and 1000μl nuclease-free sterile 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 racks; and 15 / 50ml centrifuge tube racks (all liquids and tubes mentioned above are nuclease-free and sterile).
[0516] 2. Prepare working solutions of cholesterol (Avetuo (Shanghai) Pharmaceutical Technology Co., Ltd.), DSPC alcohol (Avetuo (Shanghai) Pharmaceutical Technology Co., Ltd.), cationic lipids, and DMG-PEG2000 (Avetuo (Shanghai) Pharmaceutical Technology Co., Ltd.) in advance with anhydrous ethanol. The concentration of each working solution is 10 mg / ml. Seal and store in the refrigerator to prevent ethanol evaporation from affecting the concentration.
[0517] 3. Using cationic lipids (1-42, 44-56), cholesterol, DSPC, and DMG-PEG 2000 in a mass ratio of 50:19.25:5:0.75, and cationic lipids (43), cholesterol, DSPC, and DMG-PEG 2000 in a mass ratio of 50:35.77:9.29:1.39, mix the cationic lipids, cholesterol, DSPC, and DMG-PEG in a 1.5ml centrifuge tube. Add a certain volume of anhydrous ethanol to prepare a final concentration of 5mg / 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 25mM sodium acetate solution (pH 5.2) and add the mix dropwise to the vortexed sodium acetate buffer solution to obtain LNP.
[0518] Example 3: Preparation of LNP-mRNA complex 1
[0519] The LNP prepared in Example 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 concentration of LNP after dialysis was between 0.8-1ug / ul. The LNP:RNA (w / w) was mixed at a ratio of 10:1 and incubated for 15 minutes. The mixture was then concentrated at 5000g using a 15ml 50kDa ultrafiltration centrifuge tube and injected intratumorally as complex 1 at a volume of 30-50ul / mouse.
[0520] Example 4: Preparation of LNP-mRNA complex 2
[0521] The LNP prepared in Example 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 concentration of LNP after dialysis was between 0.8-1 μg / μL. The LNP:RNA (w / w) was mixed at a ratio of 10:1 and incubated for 15 minutes to obtain complex 2 for tail vein injection.
[0522] Example 5: Preparation of LNP-mRNA complex 3
[0523] The LNP prepared in Example 2 was mixed with RNA (w / w) at a ratio of 10:1 and incubated for 15 min to obtain complex 3 for cell transfection.
[0524] Example 6: LNP-mRNA complex delivers Luc-mRNA to RAW264.7 cells
[0525] Raw264.7 cells were seeded and cultured in 96-well plates with DMEM high-glucose medium supplemented with 10% FBS, with 2 x 10⁴ cells per well, containing penicillin (100 U / ml) and streptomycin (100 μg / ml). The LNP-luc-RNA complex 3 prepared in Example 5 was diluted with DMEM medium to an RNA concentration of 0.02 μg / μl, and 10 μl (0.2 μg RNA) was added to each well. After culturing for 20 hours, cells were lysed using a firefly luciferase reporter gene assay kit (Yeasen, 11404ES60), and the transfection efficiency of the LNP-RNA complex was determined by fluorescence analysis using a microplate reader. The results are shown below. Figure 2 As shown in the diagram (LNPs 1-56 from left to right), most of the LNPs from 1 to 56 can transfect RAW264.7 cells. For example, compounds 43, 38, 37, 28, 27, 50, 53, 23, 48, 34, 29, 10, 19, 52, 40, 7, 42, 45, 41, 25, 13, 21, 56, 3, 15, 4, 16, and 20 all showed good transfection results.
[0526] Example 7: LNP-mRNA complex delivers EGFP-mRNA to BMDM cells
[0527] 1. Prepare forceps, scissors, a 2ml syringe, a 1ml syringe, a 70µm cell filter, a 6cm dish, pre-chilled PBS, red blood cell lysis buffer, BMM medium: 10ng / ml M-CSF in DMEM complete medium; 75% ethanol; 6-well plate. Add 75% ethanol to the first well (for bone sterilization); add approximately 1mL of medium to the second and third wells (for rinsing the bone), and add 3mL of medium to the fourth well (for rinsing the bone).
[0528] 2. C57 mice were euthanized by cervical dislocation and then disinfected by soaking in 75% ethanol for 2 minutes.
[0529] 2. Make an incision along the midline of the abdomen to expose the field of vision.
[0530] 3. Next, cut the skin downwards along the femur, remove the hair, separate the femur and tibia, remove the foot, and gently rub the tissue with a tissue for best results. This can remove excess tissue (i.e., muscle and fat) from the bone.
[0531] 4. Transfer the separated femur and tibia into the first well of a six-well plate, and immerse the bones in 75% (well / volume) ethanol for 1 minute. (Do not place broken bones in ethanol.)
[0532] 5. Place them into the second well filled with 1 mL of BMM medium.
[0533] 6. Transfer them to the third well filled with 1 mL of BMM medium.
[0534] 7. Insert the needle of a 1ml syringe into a 2ml syringe and collect 2mL of fresh BMM culture medium.
[0535] 8. Remove the tibia from the petri dish and cut it at an angle at the ankle joint.
[0536] 9. Bone Marrow Collection: a. Place the tibia above a 6cm dish, keeping the narrow end of the tibia pointing downwards. b. Insert the needle into the tip of the bone marrow and spray culture medium. c. Collect 2mL of BMM culture medium from the 6cm dish, then insert the needle again. Continue rinsing several times until the bone turns white, then discard it.
[0537] 10. Add 12ml of culture medium to the 6cm dish and gently mix.
[0538] 11. Spread the cell suspension at 2 ml per well in a 6-well plate, and mark it as Day 0.
[0539] 12. Day 7: A mature BMDM was obtained.
[0540] 13. Remove the supernatant from the BMM medium in the six-well plate, wash twice with PBS, and replace with DMEM complete medium.
[0541] 14. LNPs 27, 28, 37, 38, 43, and 50 were selected to prepare LNP-EGFP-RNA complexes according to the method in Example 5. The complexes were diluted with DMEM medium to an RNA concentration of 0.02 μg / μl, and 100 μl (2 μg RNA) was added to each well. The cells were then cultured for 20 hours, and the F480 level was detected by flow cytometry (FACS). + CD11b + EGFP + The cell percentage represents the transfection efficiency of the LNP-RNA complex, as shown in the results. Figure 3-1 and Figure 3-2 As shown, LNP 43 had the highest transfection efficiency.
[0542] Example 8: LNP-mRNA complex delivers CAR-CD19 / HER2-mRNA to BMDM cells
[0543] 1. Mature BMDM cells were obtained according to the method of Example 7 (steps 1-13).
[0544] 2. LNP number 43 was selected and the LNP-CAR-CD19 / HER2-RNA complex was prepared according to the method in Example 5. The complex was diluted with DMEM medium to an RNA concentration of 0.02 μg / µl, and 100 µl (2 μg RNA) was added to each well. The cells were incubated for 20 hours, and the F480 level was detected by flow cytometry (FACS). + CD11b + CAR-HER2 + The cell percentage, representing the transfection efficiency of the LNP-mRNA complex, was generated using FlowJO analysis software, and the results are as follows: Figure 4 As shown, the transfection efficiency of LNP 43 in BMDM cells was around 14%, directly demonstrating the successful expression of CAR mRNA and the successful construction of CAR-BMDM cells.
[0545] Example 9: LNP polarizes M0-Raw264.7 cells into M1 type
[0546] Raw264.7 cells were seeded and cultured in 6-well plates with DMEM high-glucose medium (HyClone, SH30022.01B) supplemented with 10% FBS, with 1 x 10⁶ cells per well, containing penicillin (100 U / ml) and streptomycin (100 μg / ml). LNP-EGFP-RNA complexes were prepared using the method described in Example 5, with the high transfection efficiency of LNP 43 (43 cationic lipid, cholesterol, DSPC, DMG-PEG 2000 ratio of 50:35.77:9.29:1.39) and the low transfection efficiency of LNP (referred to as 43-1, 43 cationic lipid, cholesterol, DSPC, DMG-PEG 2000 ratio of 50:38.5:10:1.5). The complexes were diluted with DMEM medium to RNA concentrations of 0.02 μg / µl and 0.03 μg / µl, respectively. 100 µl (i.e., 2 μg RNA, 20 μg LNP and 3 μg RNA, 30 μg LNP) was added to each well, and LNPs without RNA encapsulation were added as a control. The cells were cultured for 20 hours. The supernatant was discarded, the cells were washed twice with PBS, scraped off with a cell scraper, and F480 was detected by flow cytometry (FACS). + CD11b + MFI of iNOS-APC cells, results as follows Figure 5-1 (EGFP-Count flow cytometry histogram) and Figure 5-2(The iNOS-Count flow cytometry histogram, generated by Flowjo analysis software, shows that LNPs not only deliver mRNA but also promote macrophage polarization from M0 to M1. The fact that empty LNPs can also cause polarization indicates that M1 polarization is primarily due to LNPs, not RNA. While LNP 43 of the same quality can cause polarization, LNP 43-1, with lower transfection efficiency, does not.) Figure 5-1 The fact that LNP #43 did not cause polarization indicates that high transfection efficiency LNPs are required for M1 polarization. Furthermore, LNP #43 only causes polarization at a certain dosage, suggesting that a certain dosage of LNP is also required for M1 polarization.
[0547] Example 10: LNP polarizes M0-BMDM cells into M1 type
[0548] 1. Mature BMDM cells were obtained according to the method of Example 7 (steps 1-13).
[0549] 2. LNPs 27, 28, 37, 38, 43, and 50 were selected and LNP-EGFP-RNA complexes were prepared according to the method in Example 5. The complexes were diluted with DMEM medium to an RNA concentration of 0.02 μg / μl, and 100 μl (2 μg RNA) was added to each well. The cells were then cultured for 20 hours, and the F480 level was detected by flow cytometry (FACS). + CD11b + The MFI of cellular iNOS-APCs represents the polarization effect of different LNPs, and the results are as follows: Figure 6-1 (Flow cytometry scatter plot, generated by Flowjo analysis software) and Figure 6-2 As shown, the polarization effect is better in BMDM, with LNP 37 and 38 being the best.
[0550] Example 11: LNP polarizes M2-BMDM cells into M0 type
[0551] 1. Mature BMDM cells were obtained according to the method of Example 7 (steps 1-13).
[0552] 2. Add 20 ng / mL IL-4 to DMEM complete medium to prepare M2 macrophage culture medium.
[0553] 3. Mature BMDM cells were cultured in M2 medium for 48 hours to obtain M2-type BMDM cells.
[0554] 4. Select LNPs 43 and 37 to prepare LNP-EGFP-mRNA complexes according to the method in Example 5. Dilute the RNA to a concentration of 0.02ug / ul with DMEM medium. Add 100ul (i.e. 2ug RNA) to each well of the mature BMDM in a 6-well plate and incubate for 20 hours to obtain EGFP-BMDM.
[0555] 5. Use a scraper to scrape off one well of the EGFP-BMDM from a six-well plate and add it to one well of the M2-type BMDM in the same six-well plate. Incubate for a total of 48 hours.
[0556] 6. Detect F480 using flow cytometry (FACS). + CD11b + The proportion of M2 type cells in cells, the results are as follows Figure 7 (Flow cytometry plot, generated by Flowjo flow cytometry analysis software) As shown, both LNPs 43 and 37 transformed M2 macrophages into M0 macrophages.
[0557] Example 12: Raji cell killing experiment
[0558] 1. Mature BMDM cells were obtained according to the method of Example 7 (steps 1-13).
[0559] 2. The LNP obtained in Example 7, number 43, was used to prepare the LNP-CAR CD19-mRNA complex according to the method in Example 5. The complex was diluted with DMEM medium to an RNA concentration of 0.02 ug / ul, 100 ul (i.e. 2 ug RNA) was added to each well, and the complex was cultured for 20 hours to obtain CAR CD19-BMDM.
[0560] 3. Add luc to the six-well plate according to E / T ratios of 20:1, 10:1, 1:1, 1:10, and 1:20 respectively. + Raji cells were used, with a final volume of 1 ml per well. The positive control consisted of only Raji cells without CAR-BMDM cells, with the volume adjusted to 1 ml using culture medium. The negative control consisted of co-incubation of BMDM cells and Raji cells. After 24 hours, the supernatant was collected and cells were lysed using a firefly luciferase reporter gene assay kit (Yeasen, 11404ES60). The fluorescence of Raji cells was then analyzed using a microplate reader. The killing ratio was calculated using the formula: (positive control fluorescence intensity - experimental group fluorescence intensity) / (positive control fluorescence intensity - background fluorescence intensity) × 100%. Results are shown below. Figure 8-1 living Figure 8-2 As shown, CAR CD19-BMDM can kill Raji cells.
[0561] Example 13: HER2 + MC38 cell killing experiment
[0562] 1. Mature BMDM cells were obtained according to the method of Example 7 (steps 1-13).
[0563] 2. The LNP 43 obtained in Example 7 was used to prepare an LNP-CAR HER2-mRNA complex according to the method in Example 5. The complex was diluted with DMEM medium to an RNA concentration of 0.02 μg / μl, and 100 μl (2 μg RNA) was added to each well. After culturing for 20 hours, CAR HER2-BMDM was obtained. This CAR HER2-BMDM was scraped off with a spatula and plated into 96-well plates, 3 x 10⁻⁶ wells per well. 4 Cells (i.e., 3*10) 3 CAR-BMDM), laid out overnight;
[0564] 3. Add luc to the 96-well plate according to the E / T ratios of 20:1, 10:1, 5:1, 2.5:1, 1:2, 1:10, and 1:20 respectively. + HER2 + MC38 cells, with a final volume of 100 μL per well; the positive control consisted of only luciferase cells. + HER2 + MC38 cells (without CAR-BMDM cells) were cultured to a volume of 100 μL. The negative control consisted of co-incubation of BMDM and Raji cells. After 24 hours, all cells in 96-well plates were lysed using a firefly luciferase reporter gene assay kit (Yeasen, 11404ES60). Cell fluorescence was analyzed using a microplate reader. The cell killing ratio was calculated as: (Negative control fluorescence intensity - Experimental group fluorescence intensity) / (Negative control fluorescence intensity - Background fluorescence intensity) × 100%. Results are shown below. Figure 9 As shown, CAR HER2-BMDM can kill HER2. + MC38 cells.
[0565] Example 14: CAR-BMDM Phagocytosis Experiment
[0566] 1. Mature BMDM cells were obtained according to the method of Example 7 (steps 1-13).
[0567] 2. The LNP obtained in Example 7 was used to prepare LNP-CAR HER2-mRNA and LNP-CAR CD19-mRNA complexes according to the method in Example 5. The RNA concentration was diluted to 0.02ug / ul with DMEM medium, 100ul (i.e. 2ug RNA) was added to each well, and the mixture was cultured for 20 hours to obtain CAR HER2-BMDM and CAR CD19-BMDM.
[0568] 3. Add EGFP to the 6-well plate at an E / T ratio of 1:3.+ HER2 + MC38 cells, EGFP + HER2 + CT26 cells, with a final volume of 1 ml per well. Negative controls included CAR CD19-BMDM cells and BMDM cells mixed with luciferase. + HER2 + MC38 cells, luc + HER2 + CT26 cells were co-incubated, and after 4 hours, F480 was detected by flow cytometry (FACS). + CD11b + Cellular EGFP + The ratio, namely the CARHER2-BMDM specific phagocytosis ratio, is as follows: Figure 10 As shown, the proportion of cells undergoing phagocytosis in BMDM is approximately 10%.
[0569] Example 15: Investigation of LNP targeting in wild-type Balb / C mice
[0570] LNPs 27, 28, 37, 43, and 50 were selected and LNP-CAR HER2-luc-mRNA complexes were prepared according to the method in Example 4. 20 μg mRNA / mouse was injected via the tail vein. Six hours later, the biofluorescence intensity distribution in the mice was measured using an IVIS small animal in vivo imaging system, as well as the biofluorescence intensity distribution in the heart, liver, spleen, lungs, kidneys, and bone marrow after dissection. Mice were intraperitoneally injected with 100 μL of D-fluorescein potassium salt (30 mg / mL, dissolved in PBS) before imaging. Results are as follows: Figure 11-1 , Figure 11-2 , Figure 11-3 As shown, LNP 37 is mainly distributed in the spleen and liver, and there is also a signal in the bone marrow. The fluorescence signal intensity of the other LNPs is lower than that of LNP 37.
[0571] Example 16: Targeting of LNP in wild-type MC38 tumor cell-bearing C57 mice
[0572] LNPs 27, 28, 37, 38, and 43 were selected and LNP-CAR HER2-luc-mRNA complexes were prepared according to the method in Example 3. 5 μg mRNA / mouse was injected intratumorally, and the biofluorescence intensity distribution in mice was measured at 6 h, 24 h, and 48 h using an IVIS small animal in vivo imaging system. Mice were intraperitoneally injected with 100 μL of D-luciferin potassium salt (30 mg / mL, dissolved in PBS) before imaging. Results are as follows: Figure 12-1 and Figure 12-2 As shown, LNP 37 was expressed at the highest level within the tumor and exhibited the best stability.
[0573] Example 17: Investigation of LNP targeting in Cre transgenic reporter mice
[0574] LNP number 37 was selected and the LNP-Cre-mRNA complex was prepared according to the method in Example 4. 10 μg and 20 μg mRNA / mouse were injected via tail vein, respectively. 48 hours later, Tdtomato in spleen and bone marrow cells were detected by flow cytometry (FACS). + Cell proportion, that is, which immune cells are delivered to the body by LNP 37. Results are as follows: Figure 13-1 and Figure 13-2 As shown, LNP 37 can transfect various immune cells in the spleen and bone marrow.
[0575] Example 18: In vivo construction and validation of the LNP-mRNA delivery system for in situ CAR-myeliod
[0576] LNP number 37 was selected and the LNP-HER2-mRNA complex was prepared according to the method in Example 4. 20 μg mRNA / mouse was injected via tail vein. Blood, bone marrow, and spleen were collected 24 hours later using orbital blood sampling. CAR-HER2 was detected by flow cytometry (FACS). + Distribution of immune cells. Results are as follows: Figure 14 As shown, LNP number 37 can generate CAR-immune cells in situ and travel to various parts of the body via the bloodstream.
[0577] Example 19: In situ CAR-immunotherapy for lung metastasis model
[0578] 1. Luc, which overexpresses the HER2 antigen, was injected via tail vein. + CT26 tumor cells were used to construct a lung metastasis model to evaluate the in vivo antitumor effect of orthotopic CAR-immune cells. Mice were randomly divided into two groups of five each. The biofluorescence intensity of the lungs was measured using an IVIS small animal in vivo imaging system to indirectly indicate tumor severity. Mice were intraperitoneally injected with 100 μL of D-fluorescein potassium salt (30 mg / mL, dissolved in PBS) before imaging.
[0579] 2. Mouse weight was measured every two days, and two sets of mouse weight change curves were plotted as follows: Figure 15 As shown, the body weight of mice in the treatment group was significantly higher than that in the control group. LNP-HER2-mRNA complex was prepared using LNP number 37 according to the method in Example 4. 20 μg mRNA / mouse was injected via tail vein, administered every 4 days for a total of 6 doses. Tumor growth was monitored using biofluorescence imaging of the tumor, such as... Figure 16As shown in the figure. Semi-quantitative fluorescence analysis of mouse lung tumors showed that on day 17 of treatment, the fluorescence intensity in the lungs of mice treated with LNP-CAR mRNA was significantly weaker than that of the control group, as shown in the figure. Figure 17 As shown, this demonstrates its good tumor-suppressive effect. The survival curves of the treatment group mice and the control group mice also showed significant differences, such as... Figure 18 As shown, this also proves that the therapy has good therapeutic effects.
[0580] Example 20: In situ CAR-immunotherapy for solid tumors
[0581] 1. A solid tumor model was established by subcutaneously inoculating CT26 tumor cells overexpressing the HER2 antigen to evaluate the anti-solid tumor effect of orthotopic CAR-immune cells. The model mice were randomly divided into an experimental group and a control group, with 9 mice in each group.
[0582] 2. The body weight and tumor size of the mice were measured every two days, and the body weight change curves of the two groups of mice were plotted (e.g., Figure 19 (as shown) and tumor size change curves (as shown) Figure 20 (As shown); the size of the tumor was measured using calipers, measuring its length (L) and width (W). The formula for calculating the tumor size is: 1 / 2 × L × W 2 .
[0583] 3. LNP number 37 was selected and the LNP-HER2-mRNA complex was prepared according to the method in Example 4. 20 μg mRNA / mouse was injected via tail vein, administered every 4 days for a total of 5 doses. On day 10 of treatment, two mice treated with LNP-CAR mRNA showed tumor regression. On day 13 of treatment, differences in weight between the two groups were observed (e.g., ...). Figure 20 As shown in the figure, this demonstrates that the therapy has good therapeutic effects.
[0584] 4. Regarding mouse body weight, long-term administration did not cause weight loss; AST testing also confirmed that LNP did not cause liver damage (e.g., Figure 21 (As shown).
[0585] 5. Immunohistochemical results showed that Ki67 expression in the experimental group mice was significantly lower than that in the control group, indicating a decrease in tumor cell proliferation capacity, while the proportion of CD3 and macrophages (F480) was significantly increased, demonstrating the effectiveness of CAR-immunotherapy (e.g., Figure 22 (As shown).
[0586] Example 21: Immunocell typing in in situ CAR-immunotherapy for solid tumors
[0587] 1. Randomly select 4 mice from each of the experimental and control groups in Example 20, and cut off the tumors;
[0588] 2. Place the tumor to be minced into a 1.5ml EP tube, add 200ul of tissue lysis buffer (Reward), and mince it with scissors until there is basically no obstruction when blowing and aspirating with a 1ml pipette;
[0589] 3. After cutting and adding more than 2 ml of the solution, transfer it to the grinding machine tube using a Pasteur tube. Then add 1 ml of tissue lysis buffer and grind the tissue using the grinding machine.
[0590] 4. After grinding, filter through a 0.45µm filter membrane, transfer to a 15ml centrifuge tube, and centrifuge at 400g for 5min; discard the supernatant, add 6ml of lysing red lysate, and lyse on ice for 5min; then centrifuge at 400g for 5min and discard the supernatant.
[0591] 6. Add 6 ml of DMEM to resuspend, centrifuge at 400 g for 5 min, discard the supernatant, resuspend in DMEM medium, and obtain a single-cell suspension;
[0592] 7. The effect of LNP treatment (No. 37) on tumor immune microenvironment reprogramming was detected by flow cytometry. According to the flow cytometry analysis, the infiltration of M2 macrophages (CD206+) was reduced in the treatment group. Figure 23 This result demonstrates that pro-tumor macrophages underwent phenotypic metastasis within the tumor microenvironment. Flow cytometry analysis of CD4+ T cells revealed increased infiltration of Tfh cells and Th1 cells in the tumor microenvironment of the treatment group. Figure 24 In 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 via LNP 37 to generate CAR-immune cells in situ increased and enhanced cytotoxic T cell activity, altering the tumor immune microenvironment.
[0593] Example 22: LNP delivers circular RNA in vivo
[0594] 1. The LNP No. 43 prepared according to Example 2 was placed in a dialysis bag (3.5K, Thermo Scientific) and dialyzed with ultrapure water at room temperature for at least 3 hours; the LNP concentration after dialysis was between 0.8-1 μg / µl. The LNP was mixed with circular lucRNA LNP at a mass ratio of 10:1 and incubated for 15 minutes. The mixture was then concentrated at 5000g using a 15ml 50kDa ultrafiltration centrifuge tube to obtain the complex for intratumoral injection, with a volume of 30-50 µl / mouse.
[0595] 2. 5 μg mRNA / mouse of the complex was injected intratumorally. The distribution of biofluorescence intensity in mice was measured using an IVIS small animal in vivo imaging system at 24 h, 48 h, and 72 h. Mice were intraperitoneally injected with 100 μL of D-fluorescein potassium salt (30 mg / mL, dissolved in PBS) before imaging. Results are as follows: Figure 26 As shown, LNP number 43 can also deliver circular RNA.
[0596] Although the embodiments of this application have been described above in conjunction with the specific embodiments described, this application is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art can make many other forms based on the teachings of this specification and without departing from the scope of protection of the claims of this application, and these are all within the scope of protection of this application.
Claims
1. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in targeting immune cells, in: G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; 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 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 a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -; Among them, R e and R f Optionally substituted C1-C12 alkylene groups; G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-; R g Optionally substituted C1-C12 alkylene groups; X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
2. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in the preparation of a medicament targeting immune cells. in: G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; 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 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 a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -; Among them, R e and R f Optionally substituted C1-C12 alkylene groups; G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-; R g Optionally substituted C1-C12 alkylene groups; X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
3. The use according to claim 1 or 2, wherein, The immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
4. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in promoting cell polarization. in: G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; 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 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 a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -; Among them, R e and R f Optionally substituted C1-C12 alkylene groups; G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-; R g Optionally substituted C1-C12 alkylene groups; X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
5. Use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof in the preparation of a drug that promotes immune cell polarization. in: G1 and G2 are each independently, optionally substituted, C2-C24 straight-chain alkylene groups; 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 heteroarylene)-; R a and R b Each 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 bonded, optionally substituted C2-C24 straight-chain alkylene groups; 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 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 a optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group; Z is optionally substituted C1-C12 alkylene or optionally substituted -R. e G7R f -; Among them, R e and R f Optionally substituted C1-C12 alkylene groups; G7 is -NR g -、-(3-7 membered saturated cycloalkane)-、-(3-7 membered heterocyclic alkane)-、-(3-7 membered cyclic arylene)- or -(3-7 membered cyclic heteroarylene)-; R g Optionally substituted C1-C12 alkylene groups; X and Y are each independently substituted C1-C12 straight-chain alkyl groups, -G1L1G3L3G5, or X, Z cyclized with the nitrogen to which they are attached.
6. The use according to claim 4 or 5, wherein, The cell polarization is from M0 type to M1 type polarization.
7. The use according to claim 4 or 5, wherein, The cell polarization is from M2 type to M0 type polarization.
8. The use according to claim 4 or 5, wherein, The cells in question are macrophages.
9. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA): in, 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.
10. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB): in, G1, G2, G3, G4, G5, G6, G7, L1, L2, L3, L4, R e R f X and Y are as defined in claim 1.
11. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G1 and G2 are unsubstituted C2-C4 alkylene groups.
12. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein L1 and L2 are -C(=O)O-.
13. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G3 and G4 are bonds.
14. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G3 and G4 are unsubstituted C2-C4 alkylene groups.
15. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein L3 and L4 are bonds.
16. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein L3 and L4 are -OC(=O)O-.
17. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
18. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-1): in, m is 1 or 3, n is 0 or 1, G5 and G6 are defined as described in claims 1-8, G8 is defined as described in claim 2, and G9 and G... 10 It is a C1-C5 straight-chain alkane that is optionally substituted.
19. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-2): in, m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
20. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-3): in, m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
21. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IA-4): in, m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
22. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB-1): in, m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as in claim 10.
23. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB-2): in, m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
24. The use according to any one of claims 1-8, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein the compound has the structure shown in formula (IB-3): in, m is 1 or 3, n is 0 or 1, and G5 and G6 are defined as described in claims 1-8.
25. The use according to claim 18, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G8 is optionally a substituted C2-C4 alkylene group.
26. The use according to claim 18, or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein G9 or G 10 Or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl.
27. The use according to any one of claims 18-24, wherein G5 or G6 or both have one of the following structures:
28. The use according to any one of claims 1-27, wherein, The compound of formula (I) or its pharmaceutically acceptable salt, prodrug, or stereoisomer is prepared as a composition for use, preferably, The composition further comprises a therapeutic or preventative agent and a carrier for delivering the therapeutic or preventative agent, the carrier comprising a cationic lipid comprising one or more of the compounds represented by formula (I) or pharmaceutically available salts thereof.
29. A method for in vitro screening of lipid nanoparticles, comprising: The first screening was conducted in macrophage cell lines to obtain lipid nanoparticles that can be transfected into macrophage cell lines; Lipid nanoparticles with FLuc fluorescence signal intensity higher than 10,000 RLUs were selected from the obtained lipid nanoparticles and subjected to a second screening in primary macrophages derived from bone marrow. The target lipid nanoparticles were obtained after the second screening.
30. The method according to claim 29, wherein, The macrophage cell line is Raw264.
7.
31. A method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising: Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene were injected into wild-type mice via the tail vein, and the first lipid nanoparticles that were expressed in a given organ and had an expression rate of more than 80% were screened. Optionally, the first lipid nanoparticles encapsulating CAR-mRNA carrying the reporter gene were screened and injected intratumorally into tumor-bearing mice. The second lipid nanoparticles were screened and expressed only at the tumor site, not in other organs, and stably expressed for 24–48 h. The first or second lipid nanoparticles obtained through screening were injected via the tail vein into Cre reporter mice, and mice with Td tomato-like immune cells were screened for. + Target lipid nanoparticles for cells.
32. The method according to claim 29, wherein, The given organ is selected from the spleen or bone marrow.
33. The method according to claim 29, wherein, The immune cells are selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
34. The method according to any one of claims 29-33, wherein, The target lipid nanoparticles are prepared from compounds of formula (I) as described in claims 1-28 or pharmaceutically acceptable salts, prodrugs or stereoisomers thereof.