WO2025166993A1 - 一种新型脂质化合物以及组合物和核酸脂质纳米颗粒制剂及其筛选方法和应用 - Google Patents

一种新型脂质化合物以及组合物和核酸脂质纳米颗粒制剂及其筛选方法和应用

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Publication number
WO2025166993A1
WO2025166993A1 PCT/CN2024/105654 CN2024105654W WO2025166993A1 WO 2025166993 A1 WO2025166993 A1 WO 2025166993A1 CN 2024105654 W CN2024105654 W CN 2024105654W WO 2025166993 A1 WO2025166993 A1 WO 2025166993A1
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independently
optionally substituted
straight
chain
alkylene
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English (en)
French (fr)
Inventor
邱敏
张晨晨
尹启蒙
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Fudan University
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Fudan University
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Priority claimed from CN202410167158.1A external-priority patent/CN120423968A/zh
Priority claimed from CN202410757306.5A external-priority patent/CN121108003A/zh
Application filed by Fudan University filed Critical Fudan University
Publication of WO2025166993A1 publication Critical patent/WO2025166993A1/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
    • C07C229/16—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Definitions

  • the present application belongs to the field of biomedicine technology, and specifically relates to a lipid compound and a lipid carrier containing the same, a nucleic acid lipid nanoparticle composition and a pharmaceutical preparation and a screening method and application thereof, an LNP-mRNA delivery system, mRNA and its use.
  • nucleic acid drugs can be used to prevent cancer, bacterial and viral infections, and treat diseases with genetic etiologies. Because nucleic acid drugs are easily degraded and difficult to enter cells, they require encapsulation with a vector for delivery to target cells. Therefore, the development of safe and efficient delivery vectors is a prerequisite for the clinical application of gene therapy.
  • Lipid nanoparticles are currently a research hotspot in the field of non-viral gene delivery. As a safe and efficient nucleic acid drug delivery vehicle, they have been shown to be able to efficiently deliver RNA to the liver.
  • the US FDA approved the world's first LNP-based liver-targeted siRNA drug. It is used to treat hereditary transthyretin-mediated amyloidosis.
  • the two COVID-19 mRNA vaccines currently approved by the US FDA are also based on LNP development.
  • LNP nucleic acid delivery systems still face several challenges, including the fact that LNPs are primarily targeted to the liver and the potential for immunogenicity.
  • LNPs are usually composed of four lipid compounds, namely cationic lipids, neutral lipids, steroids and PEG-lipids. Among them, the choice of cationic lipids has the greatest impact on LNPs, such as affecting the encapsulation rate of nucleic acid drugs, the delivery site and efficiency of nucleic acid drugs in the body, and cytotoxicity.
  • Immune cell therapies include CAR-T, CAR-NK, CAR-DC, and CAR-Macrophage. A variety of these therapies, especially CAR-T, have achieved tremendous success in the treatment of hematologic malignancies.
  • single-cell immune cell therapies still have limitations in the treatment of solid tumors. This is because the tumor microenvironment is often isolated within a dense, fibrous mass, making it difficult for immune cells to infiltrate and exert their killing effects. Furthermore, the immunosuppressive microenvironment can easily lead to cell exhaustion.
  • Traditional methods of forming CAR-immune cells in vitro and then reintroducing them into the body often suffer from low editing efficiency and long construction times. Therefore, how to form multiple CAR-immune cells in vivo, stimulate an immune response at the tumor site, and enhance the anti-tumor effect of a single CAR-immune cell remains a current challenge.
  • the first purpose of this application is to provide a series of compounds that can be used together with other lipid compounds to prepare lipid carriers to improve the delivery efficiency of nucleic acid drugs in the body.
  • Lipid compounds with specific structures can be selected as lipid carriers according to the organs where the nucleic acid drugs need to be enriched.
  • the second object of the present application is to provide a lipid carrier comprising the above compound.
  • the third object of the present application is to provide a nucleic acid lipid nanoparticle composition comprising the above compound or the above lipid carrier.
  • the fourth object of the present application is to provide a pharmaceutical preparation comprising the above-mentioned compound, or the above-mentioned lipid carrier, or the above-mentioned nucleic acid lipid nanoparticle composition.
  • the present application provides a cationic lipid compound represented by general formula (I), or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein X, Y, Z, G1 , G2 , G3 , G4 , G5 , G6 , L1 , L2 , L3 , and L4 are as defined herein or elsewhere.
  • general formula (I) or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof, wherein X, Y, Z, G1 , G2 , G3 , G4 , G5 , G6 , L1 , L2 , L3 , and L4 are as defined herein or elsewhere.
  • the present application provides a nanoparticle composition comprising a compound provided herein and a therapeutic or prophylactic agent.
  • the therapeutic or prophylactic agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof.
  • Said G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group
  • R a and R b are each independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl;
  • x 0, 1, or 2;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene group
  • R c and R d are each independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl;
  • i 0, 1, or 2;
  • Said G 5 and G 6 are each independently an optionally substituted C2-C24 straight chain alkyl group or an optionally substituted C2-C24 straight chain alkenyl group;
  • Said Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G 7 R f -;
  • R e and R f are optionally substituted C1-C12 alkylene groups
  • G 7 is -NR g -, -(3-7 membered saturated cycloalkane)-, -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-;
  • Rg is an optionally substituted C1-C12 alkylene group
  • the X and Y are each independently an optionally substituted C1-C12 straight-chain alkyl group, -G 1 L 1 G 3 L 3 G 5 , or X and Z together with the nitrogen to which they are attached form a ring.
  • G 1 , G 2 , G 3 , G 4 , G 5 , G 6 , L 1 , L 2 , L 3 , L 4 , X and Y are as defined in item 1;
  • G 8 is an optionally substituted C1-C12 alkylene group.
  • G 1 , G 2 , G 3 , G 4 , G 5 , G 6 , G 7 , L 1 , L 2 , L 3 , L 4 , Re , R f , X and Y are as defined in item 1.
  • G5 and G6 are as defined in item 10
  • G8 is as defined in item 2
  • G9 and G10 are optionally substituted C1-C5 straight-chain alkanes.
  • n is 0 or 1
  • G5 and G6 are as defined in item 10.
  • n is 0 or 1
  • G5 and G6 are as defined in item 10.
  • G 1 , G 2 , G 3 , G 4 , G 5 , G 6 , L 1 , L 2 , L 3 , L 4 and Y are as defined in item 1; and G 8 is an optionally substituted C1-C12 alkylene group.
  • n is 0 or 1
  • Y, G5 and G6 are as defined in item 1; and G8 is an optionally substituted C1-C12 alkylene group.
  • n is 0 or 1
  • Y, G5 and G6 are as defined in item 1.
  • n is 0 or 1
  • G5 and G6 are as defined in item 10.
  • n is 0 or 1
  • G5 and G6 are as defined in item 10.
  • n is 0 or 1
  • G5 and G6 are as defined in item 10.
  • G 1 , G 2 , G 3 , G 4 , G 5 , G 6 , G 7 , L 1 , L 2 , L 3 , L 4 , Re and R f are as defined in item 1.
  • a composition comprising: a therapeutic agent or a preventive agent; and a carrier for delivering the therapeutic agent or the preventive agent, wherein the carrier comprises a cationic lipid, and the cationic lipid comprises one or more of the compound represented by formula (I) described in any one of items 1 to 24, or a pharmaceutically acceptable salt thereof.
  • composition according to item 26, wherein the therapeutic or prophylactic agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof.
  • the mRNA is a monocistronic mRNA or a polycistronic mRNA.
  • composition according to item 27 wherein the antigen is a pathogenic antigen.
  • composition according to item 26 wherein the mRNA comprises one or more functional nucleotide analogs, wherein the functional nucleotide analogs are selected from one or more of pseudouridine, 1-methyl-pseudouridine or 5-methylcytosine.
  • the small molecule compound is selected from one or more of antitumor drugs, anti-infective drugs, local anesthetics, antidepressants, anticonvulsants, antibiotics/antibacterial agents, antifungals, antiparasitic drugs, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, anti-glaucoma agents, anesthetics or imaging agents.
  • composition according to item 25 wherein the mass ratio of the carrier to the therapeutic or preventive agent is 5:1 to 50:1.
  • composition according to claim 33 wherein the neutral lipid is one or more selected from phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, ceramide, sterol and derivatives thereof.
  • composition of any one of items 25 to 32, further comprising a steroid preferably, the steroid is one or more selected from cholesterol, non-sterols, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatine, tomatine, ursolic acid, ⁇ -tocopherol, and corticosteroids.
  • compositions according to any one of items 25 to 36, wherein the composition further comprises one or more lipids capable of binding to a polymer, preferably, the lipid capable of binding to a polymer is one or more selected from PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol or PEG-modified dialkylglycerol, further preferably, the molar ratio of the cationic lipid to the lipid capable of binding to a polymer is 100:1 to 20:1.
  • the carrier further comprises neutral lipids, structural lipids and polymer-conjugated lipids, and the molar ratio of the cationic lipids, the neutral lipids, the steroid lipids, and the polymer-conjugated lipids is (15-70): (1-15): (15-55): (0-3).
  • composition according to claim 25 characterized in that the composition further comprises a pharmaceutically acceptable excipient, preferably, the excipient comprises a pharmaceutically acceptable diluent.
  • a method for screening lipid nanoparticles in vitro comprising:
  • those with a FLuc fluorescence signal intensity higher than 10,000 RLUs were selected for a second screening in bone marrow-derived primary macrophages;
  • the target lipid nanoparticles were obtained after the second screening.
  • a method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery comprising:
  • Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene are injected into wild-type mice via the tail vein, and the first lipid nanoparticles expressing CAR-mRNA in a given organ are screened and obtained with an expression ratio higher than 80%.
  • the first or second lipid nanoparticle particles obtained by screening are injected into Cre reporter gene mice through the tail vein to screen and obtain target lipid nanoparticle particles having Td tomato + cells in immune cells.
  • the immune cell is selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
  • the cationic lipid compounds and compositions of the present application can be used to deliver nucleic acid drugs or small molecule drugs, enriching the types of cationic lipid compounds and having important significance for the development and application of nucleic acid preventive and therapeutic agents.
  • Macrophages constitute the largest immune cell population in the tumor microenvironment and have the ability to penetrate solid tumors and catalyze immune responses.
  • LNPs lipid nanoparticles
  • this application first screens macrophages in vitro and then further screens in vivo to obtain LNPs that construct a variety of CAR-immune cells in situ.
  • the LNP screening method for in vitro macrophage mRNA delivery provided in this application solves the problems of high primary cell dosage and long primary cell extraction time caused by direct screening of primary macrophages.
  • the LNP screening method for in vivo immune cell mRNA delivery provided in this application is simple and has good effects in constructing in situ CAR-immune cell therapy.
  • the LNP-mRNA complex provided in this application can deliver mRNA to macrophages with a short transfection time and a simple transfection method.
  • the transfection rate is 30.2%, providing a reference for cell editing methods for adoptive immunotherapy.
  • the LNP-mRNA complex provided in this application can deliver circular mRNA and can stably express it for 72 hours.
  • Some LNPs provided in this application can polarize unpolarized M0 macrophages into M1 pro-inflammatory phenotype.
  • Some LNPs provided in this application can polarize anti-inflammatory and tumor-promoting M2 macrophages into M0 type.
  • Some LNPs provided in this application can deliver mRNA to the spleen and bone marrow to produce a variety of CAR-immune cells, including T cells, macrophages, DC cells, and NK cells.
  • the LNP preparation method provided in this application is simple and has good reproducibility.
  • the delivered mRNA can be stably expressed in vivo for 48 hours and has good application prospects.
  • Figure 1 is a screening flow chart in Example 2.1;
  • FIG2 is a diagram showing the screening results of LNPs on Raw264.7 cells in Example 2.6;
  • FIG3-1 is a diagram showing the screening results of LNPs on BMDM cells by flow cytometry in Example 2.7;
  • Figure 3-2 is a diagram showing the screening transfection efficiency of LNP on BMDM cells in Example 2.7;
  • Figure 4 is a graph showing the results of LNP No. 43 transfection of CAR-HER2 mRNA into BMDM cells in Example 2.8;
  • Figure 5-1 shows the effects of LNPs (43, 43-1) with different transfection efficiencies and RNA packages of different masses on macrophage polarization in Raw264.7 cells in Example 2.9 (fluorescence expression);
  • Figure 5-2 shows the effects of LNPs (43, 43-1) with different transfection efficiencies and RNA packages of different masses on macrophage polarization (expressed by iNOS) in Raw264.7 cells in Example 2.9;
  • Figure 6-1 shows the polarization effects of different LNPs on BMDM cells in Example 2.10;
  • Figure 6-2 shows the polarization effects of different LNPs on BMDM cells in Example 2.10 (statistical results);
  • Figure 7 shows that LNPs No. 37 and 43 in Example 2.11 polarize M2-BMDM cells into M0 type
  • Figure 8-1 shows the results of CAR CD19-BMDM cells killing Raji cells in Example 2.12 (killing ratio);
  • Figure 8-2 shows the results of CAR CD19-BMDM cells killing Raji cells in Example 2.12 (fluorescence analysis detection);
  • Figure 9 is a graph showing the results of CAR HER2-BMDM cells killing HER2 + MC38 cells in Example 2.13;
  • Figure 10 is a graph showing the results of CAR HER2-BMDM cells phagocytosing HER2 + MC38 cells and HER2 + CT26 cells in Example 2.14;
  • Figure 11-1 shows the biodistribution of several LNPs in wild-type B/C mice in Example 2.15 (in vivo);
  • Figure 11-2 shows the biodistribution of several LNPs in wild-type B/C mice in Example 2.15 (after dissection);
  • Figure 11-3 is a statistical diagram showing the biodistribution of several LNPs in wild-type B/C mice in Example 2.15;
  • Figure 12-1 shows the time-dependent signal changes of various LNPs in Example 2.16 in C57 mice bearing wild-type MC38 tumor cells (in vivo);
  • Figure 12-2 shows the time-dependent signal changes of various LNPs in Example 2.16 in C57 mice bearing wild-type MC38 tumor cells;
  • Figure 13-1 shows the specificity detection results of bone marrow immune cells in Cre transgenic reporter mice in Example 2.17;
  • Figure 13-2 shows the specificity detection results of spleen immune cells in Cre transgenic reporter mice in Example 2.17;
  • Figure 14 shows the distribution of HER2 + cells in peripheral blood in Example 2.18;
  • Figure 15 is a curve showing the body weight changes of mice in the control group (UT) and the treatment group (Treated) in Example 2.19;
  • Figure 16 is a graph showing IVIS imaging results of mice in the control group (UT) and the treated group (Treated) in Example 2.19;
  • Figure 17 is a quantitative graph of the fluorescence signal of the lungs of mice in the control group (UT) and the treated group (Treated) detected by IVIS in Example 2.19;
  • Figure 18 is a survival curve of mice in the control group (UT) and the treatment group (Treated) in Example 2.19;
  • Figure 19 is a curve showing the body weight changes of mice in the control group (UT) and the treatment group (Treated) in Example 2.20;
  • Figure 20 is a curve showing changes in tumor size in mice in the control group (UT) and the treated group (Treated) in Example 2.20;
  • Figure 21 is a graph showing the AST and ALT test results of mice in the control group (UT) and the treatment group (Treated) in Example 2.20;
  • Figure 22 is the immunohistochemical analysis of tumors in the control group (UT) and the treated group (Treated) mice in Example 2.21.
  • Figure 23 is a flow cytometric analysis of M2 macrophages in the tumor sites of mice in the control group (UT) and the treated group (Treated) in Example 2.21.
  • Figure 24 is a flow cytometric analysis of CD4+ cells in the tumor sites of mice in the control group (UT) and the treated group (Treated) in Example 2.21.
  • Figure 25 is a flow cytometric analysis of CD8+ cells in the tumor sites of mice in the control group (UT) and the treated group (Treated) in Example 2.21.
  • Figure 26 is the IVIS imaging results of the tumor site 24h, 48h, and 72h after LNP delivery of cyclic Luc mRNA in Example 2.22.
  • lipid refers to a group of organic compounds that include, but are not limited to, fatty acid esters and are generally characterized by being poorly soluble in water but soluble in many non-polar organic solvents. Although lipids generally have poor water solubility, certain classes of lipids (e.g., lipids modified with polar groups, such as DMG-PEG2000) have limited water solubility and are soluble in water under certain conditions. Known lipid types include biomolecules such as fatty acids, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, and phospholipids.
  • biomolecules such as fatty acids, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, and phospholipids.
  • Lipids can be divided into at least three categories: (1) “simple lipids,” which include fats and oils, as well as waxes; (2) “compound lipids,” which include phospholipids and glycolipids (e.g., DMG-PEG2000); and (3) “derivatized lipids,” such as steroids.
  • lipids also include lipid-like compounds.
  • lipid nanoparticle refers to a particle with at least one nanometer (nm) size (e.g., 1 to 1,000 nm) containing one or more types of lipid molecules.
  • the LNP provided herein may further contain at least one non-lipid payload molecule (e.g., one or more nucleic acid molecules) or a small molecule drug.
  • the LNP comprises a non-lipid payload molecule partially or completely encapsulated in a lipid shell.
  • the payload is a negatively charged molecule (e.g., mRNA encoding a viral protein), and the lipid component of the LNP comprises at least one cationic lipid.
  • cationic lipids can interact with negatively charged payload molecules and promote the incorporation and/or encapsulation of payload into the LNP during LNP formation.
  • Other lipids that can form a part for the LNP provided herein include, but are not limited to, neutral lipids and charged lipids, such as steroids or their analogs, polymer-bound lipids, and various zwitterionic lipids.
  • cationic lipid refers to a lipid capable of being positively charged.
  • exemplary cationic lipids include one or more positively charged amine groups.
  • Preferred cationic lipids are ionizable so that they can be ionized depending on pH. The ionization of cationic lipids affects the surface charge of lipid nanoparticles under different pH conditions.
  • This charge state can affect plasma protein absorption, blood clearance and tissue distribution (Semple, SC et al., Adv Drug Deliv Rev 32:3-17 (1998)) and the ability (Hafez, IM et al., Gene Ther 8:1188-1196 (2001)) of forming endosome dissolution (endosomolytic) non-double-layer structure, which is crucial for the intracellular delivery of nucleic acid.
  • steroid is a compound comprising the following carbon skeleton:
  • Non-limiting examples of steroids include cholesterol and the like.
  • neutral lipids that can be used in conjunction with the present disclosure include, but are not limited to, phosphatidylcholines, such as 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC); phosphatidylethanolamines, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 2-((2,3-bis(oleoyloxy)propyl))dimethylammonio)ethyl hydrogenphosphate (DOCP); sphingomyelin (DOPE), 2-(
  • alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (tert-butyl), 3-methylhexyl, 2-methylhexyl, etc. Unless otherwise indicated, an alkyl group is optionally substituted.
  • alkenyl refers to the straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, which contains one or more carbon-carbon double bonds. It will be appreciated by those skilled in the art that term “ alkenyl " also includes groups with “ cis “ and “ trans “ configurations, or with " E “ and “ Z “ configurations.
  • alkenyl has, for example, two to twenty-four carbon atoms (C2-C24 alkenyl), four to twenty carbon atoms (C4-C20 alkenyl), six to sixteen carbon atoms (C6-C16 alkenyl), six to nine carbon atoms (C6-C9 alkenyl), two to fifteen carbon atoms (C2-C15 alkenyl), two to twelve carbon atoms (C2-C12 alkenyl), two to eight carbon atoms (C2-C8 alkenyl) or two to six carbon atoms (C2-C6 alkenyl) and it is connected to the remainder of the molecule by a single bond.
  • C2-C24 alkenyl has, for example, two to twenty-four carbon atoms (C2-C24 alkenyl), four to twenty carbon atoms (C4-C20 alkenyl), six to sixteen carbon atoms (C6-C16 alkenyl), six to nine carbon atoms (C6-C9 alkeny
  • alkenyl groups include, but are not limited to, vinyl, prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1,4-dienyl, etc. Unless otherwise specified, alkenyl groups are optionally substituted.
  • alkynyl refers to a straight or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing one or more carbon-carbon triple bonds.
  • an alkynyl group has, for example, two to twenty-four carbon atoms (C2-C24 alkynyl), four to twenty carbon atoms (C4-C20 alkynyl), six to sixteen carbon atoms (C6-C16 alkynyl), six to nine carbon atoms (C6-C9 alkynyl), two to fifteen carbon atoms (C2-C15 alkynyl), two to twelve carbon atoms (C2-C12 alkynyl), two to eight carbon atoms (C2-C8 alkynyl) or two to six carbon atoms (C2-C6 alkynyl) and is connected to the rest of the molecule by a single bond.
  • alkynyl groups include, but are not limited to, e
  • cyclization refers to partial or complete connection within or between molecules to form a cyclic molecular structure.
  • the connection points may be, but are not limited to, one C or N or several C or N groups.
  • the cyclized molecular structure may be saturated or unsaturated. Unless otherwise indicated, the cyclized molecular portion is optionally substituted.
  • the term “optionally” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.
  • “optionally substituted alkyl” means that the alkyl group may or may not be substituted, and that the description includes both substituted alkyl groups and alkyl groups without substitution.
  • prodrug refers to a derivative of a compound or nucleic acid drug of the present application that can be provided directly or indirectly after being applied to a patient.
  • the prodrug of a composition can be prepared by modifying the functional group present in a compound or nucleic acid (DNA, ASO, siRNA, mRNA, tRNA) in such a way that the modification can be cleaved in a conventional operation or in vivo to obtain a parent compound or nucleic acid.
  • Particularly preferred prodrugs are compounds and nucleic acid drugs (e.g., more easily absorbed into the blood) that can improve the bioavailability of the composition of the present application when administered to a patient, or compounds and nucleic acid drugs that promote the delivery of the parent compound to the site of action (e.g., lymphatic system).
  • nucleic acid drugs e.g., more easily absorbed into the blood
  • nucleic acid drugs that promote the delivery of the parent compound to the site of action (e.g., lymphatic system).
  • all prodrug forms of the compound of the present application are within the scope of the present application, and various prodrug forms are well known in the art.
  • the term “pharmaceutically acceptable salt” includes both acid addition salts and base addition salts.
  • Examples of pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; and organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, hexanoic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, Gluconic acid
  • Examples of pharmaceutically acceptable base addition salts include, but are not limited to, salts prepared by adding an inorganic base or an organic base to a free acid compound.
  • Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like.
  • the inorganic salt is an ammonium salt, a sodium salt, a potassium salt, a calcium salt, and a magnesium salt.
  • Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines; substituted amines, including naturally occurring substituted amines; cyclic amines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, deanol, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like.
  • basic ion exchange resins
  • the compound provided herein may contain one or more asymmetric centers, and therefore enantiomers, diastereomers and other stereoisomeric forms may be produced, which may be defined as (R)- or (S)- or as (D)- or (L)- for amino acids according to absolute stereochemistry. Unless otherwise indicated, the compound provided herein is intended to include all such possible isomers, as well as racemic and optically pure forms thereof. When the compound described herein contains olefinic double bonds or other geometric asymmetric centers, unless otherwise indicated, the compound is intended to include E and Z geometric isomers. Similarly, all tautomeric forms are also intended to be included.
  • the term “isomer” refers to different compounds having the same molecular formula.
  • “Stereoisomers” are isomers that differ only in the arrangement of their atoms in space.
  • “Atropisomers” are stereoisomers resulting from hindered rotation about a single bond.
  • “Enantiomers” are a pair of stereoisomers that are non-superimposable mirror images of each other. A mixture of a pair of enantiomers in any proportion is referred to as a “racemic” mixture.
  • “Diastereomers” are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.
  • nucleic acid refers to a polymer of nucleotides of any length and includes, for example, DNA and RNA. Nucleotides may be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases and/or analogs thereof, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. Nucleic acids may be in single-stranded or double-stranded form. As used herein and unless otherwise indicated, “nucleic acid” also includes nucleic acid mimetics such as locked nucleic acids (LNA), peptide nucleic acids (PNA) and morpholino nucleic acids.
  • LNA locked nucleic acids
  • PNA peptide nucleic acids
  • morpholino nucleic acids morpholino nucleic acids
  • oligonucleotide refers to a short synthetic polynucleotide that is generally, but not necessarily, less than about 200 nucleotides in length.
  • the terms “oligonucleotide” and “polynucleotide” are not mutually exclusive. The above description of polynucleotides applies equally and fully to oligonucleotides. Unless otherwise indicated, the left-hand end of any single-stranded polynucleotide sequence disclosed herein is the 5'end; the left-hand direction of a double-stranded polynucleotide sequence is referred to as the 5' direction.
  • Nascent RNA transcription The direction of 5′ to 3′ addition of transcripts is called the transcription direction; the sequence region on the DNA strand that has the same sequence as the RNA transcript and is located at the 5′ end relative to the 5′ end of the RNA transcript is called the “upstream sequence”; the sequence region on the DNA strand that has the same sequence as the RNA transcript and is located at the 3′ end relative to the 3′ end of the RNA transcript is called the “downstream sequence”.
  • Isolated nucleic acid refers to nucleic acid, such as RNA, DNA or mixed nucleic acid, that is substantially separated from other genomic DNA sequences and proteins or complexes (such as ribosomes and polymerases) that naturally accompany native sequences.
  • the nucleic acid molecule of " separation " is a nucleic acid molecule separated from other nucleic acid molecules that are present in the natural source of nucleic acid molecule.
  • the nucleic acid molecule of " separation " such as mRNA molecule, can be substantially free of other cell materials or culture medium, or when chemically synthesized, it can be substantially free of chemical precursors or other chemicals.
  • nucleic acid molecules of encoding antigens described herein are separated or purified.
  • the term includes nucleic acid sequences removed from its naturally occurring environment, and includes recombinant or cloned DNA or RNA isolates and chemically synthesized analogs or analogs biosynthesized by heterologous systems.
  • Substantially pure molecules can include isolated forms of molecules.
  • coding nucleic acid or its grammatical equivalents when used to refer to a nucleic acid molecule includes: (a) a nucleic acid molecule that can be transcribed to produce mRNA and then translated into peptides and/or polypeptides when in its natural state or manipulated by methods well known to those skilled in the art; and (b) the mRNA molecule itself.
  • the antisense strand is the complementary sequence of such a nucleic acid molecule, and the coding sequence can be inferred therefrom.
  • coding region refers to the portion of a coding nucleic acid sequence that is translated into a peptide or polypeptide.
  • UTR untranslated region
  • 5'-UTR a coding nucleic acid that is not translated into a peptide or polypeptide.
  • the UTR is referred to as a 5'-UTR if it is located at the 5' end of the coding region, and as a 3'-UTR if it is located at the 3' end of the coding region.
  • mRNA refers to a messenger RNA molecule comprising one or more open reading frames (ORFs), which can be translated by a cell or organism having the mRNA to produce one or more peptide or protein products.
  • ORFs open reading frames
  • the region containing one or more ORFs is referred to as the coding region of the mRNA molecule.
  • the mRNA molecule further comprises one or more untranslated regions (UTRs).
  • the mRNA is a monocistronic mRNA comprising only one ORF.
  • the monocistronic mRNA encodes a peptide or protein comprising at least one epitope of a selected antigen (e.g., a pathogenic antigen or a tumor-associated antigen).
  • the mRNA is a polycistronic mRNA comprising two or more ORFs.
  • the polycistronic mRNA encodes two or more peptides or proteins that may be identical or different from each other.
  • each peptide or protein encoded by the polycistronic mRNA comprises at least one epitope of a selected antigen.
  • the different peptides or proteins encoded by the polycistronic mRNA each comprise at least one epitope of a different antigen.
  • the at least one epitope may be at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 epitopes of an antigen.
  • nucleobase encompasses purines and pyrimidines, including the natural compounds adenine, thymine, guanine, cytosine, uracil, inosine, and natural or synthetic analogs or derivatives thereof.
  • the term "functional nucleotide analogue” refers to a modified version of a classical nucleotide A, G, C, U, or T that (a) retains the base pairing properties of the corresponding classical nucleotide and (b) contains at least one chemical modification of the (i) nucleobase, (ii) sugar group, (iii) phosphate group, or (iv) any combination of (i) to (iii) of the corresponding natural nucleotide.
  • base pairing encompasses not only the classical Watson-Crick adenine-thymine, adenine-uracil, or guanine-cytosine base pairs, but also base pairs formed between a classical nucleotide and a functional nucleotide analogue, or between a pair of functional nucleotide analogues, wherein the arrangement of hydrogen bond donors and hydrogen bond acceptors allows hydrogen bonds to form between the modified nucleobase and the classical nucleobase, or between two complementary modified nucleobase structures.
  • a functional analogue of guanosine (G) retains the ability to base pair with cytosine (C) or a functional analogue of cytosine.
  • nucleic acid molecules containing functional nucleotide analogs can have at least one modified nucleobase, sugar group and/or internucleoside linkage.
  • the application provides exemplary chemical modifications to the nucleobase, sugar group or internucleoside linkage of nucleic acid molecules.
  • translational enhancer element refers to regions in nucleic acid molecules that promote translation of a coding sequence of a nucleic acid into a protein or peptide product, such as via cap-dependent or cap-independent translation.
  • TEEs are typically located in the UTR region of a nucleic acid molecule (e.g., mRNA) and enhance the translation level of a coding sequence located upstream or downstream.
  • a TEE in the 5'-UTR of a nucleic acid molecule may be located between the promoter and the start codon of the nucleic acid molecule.
  • TEE sequences are known in the art (Wellensiek et al., Genome-wide profiling of human cap-independent translation-enhancing elements, Nature Methods, August 2013; 10(8):747-750; Chappell et al., PNAS, June 29, 2004, 101(26)9590-9594). Some TEEs are known to be conserved across multiple species (Pánek et al., Nucleic Acids Research, Vol. 41, No. 16, Sept. 1, 2013, pp. 7625-7634).
  • peptide refers to a polymer containing from two to fifty (2-50) amino acid residues linked by one or more covalent peptide bonds.
  • the term applies to naturally occurring amino acid polymers as well as amino acid polymers in which one or more amino acid residues are non-naturally occurring amino acids (e.g., amino acid analogs or non-natural amino acids).
  • polypeptide and protein are used interchangeably herein to refer to a polymer having more than fifty (50) amino acid residues linked by covalent peptide bonds. That is, a description of a polypeptide equally applies to a description of a protein, and vice versa.
  • the terms apply to naturally occurring amino acid polymers as well as amino acid polymers in which one or more amino acid residues is a non-naturally occurring amino acid (e.g., an amino acid analog).
  • the terms encompass amino acid chains of any length, including full-length proteins (e.g., antigens).
  • An “epitope” is a site on the surface of an antigen molecule that binds to a single antibody molecule, such as a localized area on an antigen surface that is capable of binding to one or more antigen-binding regions of an antibody and that has antigenic or immunogenic activity in an animal, such as a mammal (e.g., a human), and is capable of eliciting an immune response.
  • An epitope with immunogenic activity is a portion of a polypeptide that elicits an antibody response in an animal.
  • An epitope with antigenic activity is a portion of a polypeptide that is bound by an antibody as determined by any method known in the art, including, for example, immunoassays.
  • An antigenic epitope is not necessarily immunogenic.
  • the present application provides a compound of formula (I):
  • Said G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group
  • R a and R b are each independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl;
  • x 0, 1, or 2;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene group
  • R c and R d are each independently H, optionally substituted C1-C12 alkyl or optionally substituted C1-C12 alkenyl;
  • i 0, 1, or 2;
  • Said G 5 and G 6 are each independently an optionally substituted C2-C24 straight chain alkyl group or an optionally substituted C2-C24 straight chain alkenyl group;
  • Said Z is an optionally substituted C1-C12 alkylene group, an optionally substituted -R e G 7 R f -;
  • R e and R f are optionally substituted C1-C12 alkylene groups
  • G 7 is -NR g -, (3-7 membered saturated cycloalkane), -(3-7 membered heterocycloalkane)-, -(3-7 membered cyclic arylene)-, or -(3-7 membered cyclic heteroarylene)-;
  • Rg is an optionally substituted C1-C12 alkylene group
  • Said X and Y are each independently an optionally substituted C1-C12 straight chain alkyl, -G 1 L 1 G 3 L 3 G 5 , or X, Z together with the nitrogen to which they are attached form a ring;
  • Z is an optionally substituted C1-C12 alkylene group, and the compound is of the structure of formula (IA):
  • G 1 , G 2 , G 3 , G 4 , G 5 , G 6 , L 1 , L 2 , L 3 , L 4 , X and Y are as defined in formula (I), and G 8 is an optionally substituted C1-C12 alkylene group.
  • the optionally substituted -R e G 7 R f - the compound has the structure shown in formula (IB):
  • said G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene
  • said G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • said G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene group
  • L 3 and L 4 are a bond
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight chain alkylene
  • G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups
  • said G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5 ;
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight chain alkylene group;
  • X is an optionally substituted C1-C3 straight -chain alkyl group
  • Y is -G1L1G3L3G5
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G1L1G3L3G5
  • 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
  • Z is C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • X is an optionally substituted C1-C3 straight-chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G 1 L 1 G 3 L 3 G 5
  • Y is an optionally substituted C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene groups
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X is an optionally substituted C1-C3 straight-chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • X is an optionally substituted C1- C3 straight-chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • X is an optionally substituted C1-C3 straight -chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G 1 L 1 G 3 L 3 G 5
  • Y is an optionally substituted C1-C3 straight chain alkyl
  • Z is an optionally substituted wherein -R e G 7 R f -, R e and R f are optionally substituted C2-C4 alkylene, G 7 is -(3-7 membered heterocycloalkane)-;
  • said G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene;
  • said G 3 and G 4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene;
  • X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • X and Y are each independently -G1L1G3L3G5
  • Z is C2- C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • X is an optionally substituted C1- C3 straight-chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • X is an optionally substituted C1-C3 straight -chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is C2- C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight -chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is C2- C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight-chain alkyl group
  • Y is -G 1 L 1 G 3 L 3 G 5
  • Z is a C2-C4 alkylene group
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G 3 and G 4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G 5 and G 6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is C2- C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X is -G 1 L 1 G 3 L 3 G 5
  • Y is an optionally substituted C1-C3 straight chain alkyl
  • Z is a C2-C4 alkylene group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene groups
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is C2- C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently said L 3 and L 4 are each independently a bond
  • said G 5 and G 6 are each independently an optionally substituted C2-C24 straight chain alkyl group, an optionally substituted C2-C24 straight chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight -chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is C2- C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight -chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond or an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl or an optionally substituted C2-C24 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C2-C24 straight-chain alkyl group, or an optionally substituted C2-C24 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight -chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight chain alkylene;
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight chain alkylene;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight chain alkenyl.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each independently a bond, an optionally substituted C2-C24 straight-chain alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene group;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight-chain alkyl
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocycloalkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight-chain alkyl
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is optionally substituted -Re G 7 R f -
  • Re and R f are optionally substituted C2-C4 alkylene
  • G 7 is -(3-7 membered heterocyclic alkane)-
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • G 5 and G 6 are each independently an optionally substituted C4-C16 Straight chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group, Z is a C2-C4 alkylene group, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X is an optionally substituted C1-C3 straight-chain alkyl
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G 1 L 1 G 3 L 3 G 5
  • Y is an optionally substituted C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene group
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are each a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G 1 L 1 G 3 L 3 G 5
  • Y is an optionally substituted C1-C3 straight-chain alkyl
  • Z is an optionally substituted -R e G 7 R f -, R e and R f are optionally substituted C2-C4 alkylene
  • G 7 is -(3-7 membered heterocyclic alkane)-
  • said G 1 and G 2 are each are each independently an optionally substituted C2-C24 straight chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G3 and G4 are each a bond or an unsubstituted C2-C4 alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight-chain alkyl
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G 1 L 1 G 3 L 3 G 5
  • Y is an optionally substituted C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • G 1 and G 2 are each independently an optionally substituted C2-C24 straight-chain alkylene group
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene group
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight -chain alkyl
  • Y is -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an optionally substituted C2-C24 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently an optionally substituted C1-C3 straight chain alkyl group, and Z is a C2-C4 alkylene group;
  • said G5 and G6 are each independently an optionally substituted C4-C16 straight chain alkenyl.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • G 5 and G 6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1- C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • X, Z together with the nitrogen to which they are connected, form a ring
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • G 5 and G 6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight chain alkyl
  • Y is -G 1 L 1 G 3 L 3 G 5
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • said G3 and G4 are a bond or an unsubstituted C2-C4 alkylene
  • said G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl group
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight-chain alkyl
  • Y is -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 -C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl group
  • Z is a C2-C4 alkylene group
  • X, Z together with the nitrogen to which they are connected, form a ring
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight-chain alkyl
  • Y is -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 -C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently a C1-C3 straight-chain alkyl, Z is a C2-C4 alkylene, and X, Z together with the nitrogen to which they are connected form a ring;
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl group, and Z is a C2-C4 alkylene group;
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group;
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group;
  • L3 and L4 are each independently a bond;
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X and Y are each independently -G 1 L 1 G 3 L 3 G 5
  • Z is C2-C4 alkylene
  • G 1 and G 2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight - chain alkyl group
  • Y is -G1L1G3L3G5
  • Z is a C2-C4 alkylene group
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene group
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene group
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl group.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is a C2-C4 alkylene
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently an optionally substituted C1-C3 straight-chain alkyl
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2- C4 alkylene
  • G7 is -(3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are each a bond or an unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • X and Y are each independently -G1L1G3L3G5
  • Z is optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2 - C4 alkylene
  • G7 is - ( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is an optionally substituted C1-C3 straight chain alkyl
  • Y is -G 1 L 1 G 3 L 3 G 5
  • Z is an optionally substituted -R e G 7 R f -, R e and R f are optionally substituted C2-C4 alkylene
  • G 7 is -(3-7 membered heterocycloalkane)-
  • G 1 and G 2 are each independently unsubstituted C2-C4 straight-chain alkylene
  • G 3 and G 4 are a bond or unsubstituted C2-C4 alkylene
  • L 3 and L 4 are each independently a bond
  • G 5 and G 6 are each independently optionally substituted C4-C16 straight-chain alkenyl.
  • X is -G1L1G3L3G5
  • Y is an optionally substituted C1-C3 straight - chain alkyl
  • Z is an optionally substituted -ReG7Rf-
  • Re and Rf are optionally substituted C2-C4 alkylene
  • G7 is -( 3-7 membered heterocyclic alkane)-
  • G1 and G2 are each independently an unsubstituted C2-C4 straight-chain alkylene
  • G3 and G4 are a bond or an unsubstituted C2-C4 alkylene
  • L3 and L4 are each independently a bond
  • G5 and G6 are each independently an optionally substituted C4-C16 straight-chain alkenyl.
  • G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups
  • G8 is defined as in formula (IA)
  • G9 and G10 are optionally substituted C1-C5 straight-chain alkane.
  • G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
  • G 1 , G 2 , G 3 , G 4 , G 5 , G 6 , L 1 , L 2 , L 3 , L 4 and Y are as defined in the compound represented by (I); and G 8 is an optionally substituted C1-C12 alkylene group.
  • n is 0 or 1
  • Y, G5 and G6 are as defined in the compound represented by (I); and G8 is an optionally substituted C1-C12 alkylene group.
  • G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
  • G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
  • G5 and G6 are optionally substituted C4-C16 straight-chain alkenyl groups.
  • G 8 is an optionally substituted C2-C4 alkylene group
  • G 9 or G 10 or both have one of the following structures: methyl, ethyl, 2-hydroxyethyl;
  • G 5 or G 6 or both have one of the following structures:
  • the present application further provides a composition comprising a therapeutic agent or a prophylactic agent; and a carrier for delivering the therapeutic agent or the prophylactic agent, wherein the carrier comprises a cationic lipid, and the cationic lipid comprises one or more of the cationic lipid compounds provided in any of the above applications, or their pharmaceutically acceptable salts.
  • the therapeutic agent or preventive agent can be a nucleic acid molecule, a small molecule compound, a polypeptide or a protein, or a mixture of two or more thereof.
  • the nucleic acid molecule is selected from single-stranded DNA, double-stranded DNA, short isomers, agomir, antagomir, antisense molecules, small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicersubstrate RNA (dsRNA), small hairpin RNA (shRNA), transfer RNA (tRNA), messenger RNA (mRNA) and other forms of RNA molecules known in the art, or nucleic acid mimics such as locked nucleic acid (LNA), peptide nucleic acid (PNA) and morpholino oligonucleotides.
  • LNA locked nucleic acid
  • PNA peptide nucleic acid
  • morpholino oligonucleotides morpholino oligonucleotides
  • the therapeutic agent or preventive agent comprises at least one mRNA encoding an antigen or a fragment or epitope thereof.
  • the mRNA is a monocistronic mRNA or a polycistronic mRNA.
  • the antigen is a pathogenic antigen.
  • the mRNA contains one or more functional nucleotide analogs.
  • the functional nucleotide analogs are selected from one or more of pseudouridine, 1-methyl-pseudouridine or 5-methylcytosine.
  • the small molecule compound is selected from one or more of antitumor drugs, anti-infective drugs, local anesthetics, antidepressants, anticonvulsants, antibiotics/antibacterial agents, antifungals, antiparasitic drugs, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, anti-glaucoma agents, anesthetics or imaging agents.
  • the amount of the carrier and the therapeutic agent or preventive agent is not limited in this application.
  • the mass ratio of the carrier to the therapeutic agent or preventive agent is 1.5:2 to 50:1, for example, it can be 0.75:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 25:1, 30:1, 35:1, 40:1, 41:1, 42:1, 43:1, 44:1 1, 45:1, 46:1, 47:1, 48:1, 49:1.
  • the cell polarization is from M0 type to M1 type polarization.
  • the immune cells are selected from lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells, preferably macrophages.
  • the present application further provides a method for in vitro screening of lipid nanoparticles, comprising:
  • those with a FLuc fluorescence signal intensity higher than 10,000 RLUs were selected for a second screening in bone marrow-derived primary macrophages;
  • the target lipid nanoparticles were obtained after the second screening.
  • the macrophage cell line is the Raw264.7 cell line.
  • the FLuc fluorescence signal intensity is higher than 10,000 RLUs and may be higher than 20,000 RLUs, 30,000 RLUs, 40,000 RLUs, 50,000 RLUs, 60,000 RLUs, 70,000 RLUs, 80,000 RLUs, 90,000 RLUs, 100,000 RLUs, 110,000 RLUs, 120,000 RLUs, 130,000 RLUs, 140,000 RLUs, 150,000 RLUs, 160,000 RLUs, 170,000 RLUs, 180,000 RLUs, 190,000 RLUs, 200,000 RLUs and above.
  • the present application further provides a method for screening lipid nanoparticles suitable for in vivo immune cell mRNA delivery, comprising:
  • Lipid nanoparticles encapsulating CAR-mRNA carrying a reporter gene are injected into wild-type mice via the tail vein, and the first lipid nanoparticles expressing CAR-mRNA in a given organ are screened and obtained with an expression ratio higher than 80%.
  • the first lipid nanoparticles obtained by screening are encapsulated with CAR-mRNA carrying a reporter gene and injected intratumorally into tumor-bearing mice to screen for expression of the second lipid nanoparticles only in the tumor site and not in other organs, and stably expressing for 24 to 48 hours; the other organs refer to organs without tumors;
  • the first or second lipid nanoparticle particles obtained by screening are injected into Cre reporter gene mice through the tail vein to screen and obtain target lipid nanoparticle particles having Td tomato + cells in immune cells.
  • the given organ is selected from the spleen or bone marrow.
  • the immune cell is selected from any one of lymphocytes, dendritic cells, macrophages, granulocytes, and mast cells.
  • the target lipid nanoparticles as described above are prepared from the compound of formula (I) provided in the present application or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof.
  • the raw materials used can be obtained commercially.
  • N,N-dimethylethylenediamine (30 ⁇ L, 0.33 mmol, 1 eq) and compound 1-2 (300 ⁇ L, 1.01 mmol, 3 eq) were mixed and stirred at 70 ° C. for 48 h.
  • the mixture was purified by column chromatography (silica gel column, eluent: dichloromethane solution containing 0-10% methanol (volume percentage)) to give compound 1 (370 mg, 54%) as a slightly yellow oil.
  • Compound 29 was prepared by the method described in Example 1.1.
  • the synthetic route is as follows:
  • N,N-dimethylethylenediamine (32 ⁇ L, 0.36 mmol, 1 eq) and compound 33-1 (300 ⁇ L, 1.09 mmol, 3 eq) were mixed and stirred at 70°C for 48 h.
  • the mixture was purified by column chromatography (silica gel column, eluent: dichloromethane solution containing 0-10% methanol (volume percentage)) to give compound 33 (380 mg, 60%) as a slightly yellow oil.
  • the 56 cationic lipid compounds prepared in Examples 1.1-56 were dissolved in anhydrous ethanol with cholesterol (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.), DSPC alcohol (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.), and DMG-PEG2000 (Aiweituo (Shanghai) Pharmaceutical Technology Co., Ltd.) at a molar ratio of 66.67:25.67:6.67:1.00.
  • Lipid nanoparticles (LNPs) were prepared at a weight ratio of approximately 10:1 between the cationic lipid and firefly luciferase (Fluc) mRNA.
  • mRNA was diluted in 25 mM sodium acetate solution (pH 5.2), and the ethanolic lipid solution was mixed with the mRNA aqueous solution at a ratio of approximately 1:3 (volume/volume) using a syringe pump at a total flow rate of 12 mL/min.
  • the ethanol was removed by dialysis, and the LNPs were then replaced in ddH2O .
  • the lipid nanoparticles were filtered through a 0.2 ⁇ m pore sterile filter to obtain an LNP formulation encapsulating firefly luciferase mRNA (LNP-mFluc).
  • the lipid nanoparticle composition (LNP-mFluc) prepared in Example 1.57 was separately evaluated for luciferase mRNA in vivo.
  • FLuc mRNA from Shanghai Hexincheng Biotechnology expresses luciferase protein, originally isolated from fireflies. Fluc is commonly used in mammalian cell culture to measure gene expression and cell viability. It emits bioluminescence in the presence of the substrate luciferin. Studies were conducted in 5-6 week old female Balb/c mice (Shanghai Slake Laboratory Animal Co., Ltd.) according to the guidelines established by the Committee on Care of Animals (ACC) and the Canadian Council on Animal Care (CCAC).
  • ACC Committee on Care of Animals
  • CCAC Canadian Council on Animal Care
  • mice 50 ⁇ g of cationic lipid nanoparticles containing 5 ⁇ g of luciferase mRNA were injected via the tail vein.
  • 100 ⁇ L of 30 mg/mL D-luciferin potassium salt (Adamas Reagent Co., Ltd.) was intraperitoneally injected into the mice.
  • the mice were imaged using an in vivo imaging system (PerkinElmer).
  • PerkinElmer the compounds with strong fluorescence intensity in the liver and their specific fluorescence values are shown in Table 2.
  • Compound 9, compound 32, compound 21, compound 8, compound 10, compound 33, compound 16, compound 30, compound 15, compound 2, compound 51, compound 56, compound 26, compound 25, compound 29, compound 5, compound 42, compound 53, compound 52, compound 13, and compound 50 have strong fluorescence signals in the spleen, with fluorescence intensities generally above about 1.17E+07, especially compound 50, with a maximum fluorescence intensity of 1.03E+08.
  • Compound 17, which has a strong signal in the lungs, has a fluorescence signal intensity of approximately 6.95E+05.
  • Step 1 LNPs from the LNP library were encapsulated with luc-mRNA and transfected into the RAW264.7 macrophage cell line for preliminary screening. The cells were lysed and detected by a microplate reader, and the Luc fluorescence intensity represented the transfection efficiency.
  • Step 2 LNPs with higher transfection efficiency in the cell line were selected, and LNPs were encapsulated with EGFP-mRNA and transfected into primary macrophages derived from mouse bone marrow (BMDM) for further fine screening. The proportion of EGFP-positive cells was detected by flow cytometry to represent the transfection efficiency. Finally, the target LNPs for in vitro transfection of primary macrophages were obtained.
  • BMDM mouse bone marrow
  • the mass ratio of cationic lipids (No. 1-42, No. 44-56), cholesterol, DSPC, and DMG-PEG 2000 is 50:19.25:5:0.75; the mass ratio of cationic lipid (No. 43), cholesterol, DSPC, and DMG-PEG 2000 is 50: 35.77:9.29:1.39, cationic lipid, cholesterol, DSPC, and DMG-PEG were mixed in a 1.5 ml centrifuge tube, and a certain volume of anhydrous ethanol was added to prepare a final concentration of 5 mg/ml mix. The mixture was vortexed for 1 min to mix evenly, sonicated for 1 min, and continued to vortex for 1 min. In addition, 3 times the volume of 25 mM sodium acetate solution (pH 5.2) was taken and the mix was uniformly dripped into the vortexed sodium acetate buffer to obtain LNP.
  • the LNP prepared in Example 2.2 was placed in a dialysis bag (3.5K, Thermo Scientific) and dialyzed with ultrapure water at room temperature for more than 3 hours.
  • the concentration of LNP after dialysis was between 0.8 and 1 ug/ul.
  • Example 2.6 Delivery of Luc-mRNA to RAW264.7 cells by LNP-mRNA complexes
  • Raw264.7 cells were seeded and cultured in 96-well plates in DMEM high-glucose medium supplemented with 10% FBS, with 2x104 cells per well. Penicillin (100 U/ml) and streptomycin (100 ⁇ g/ml) were added to the culture medium.
  • LNP-luc-RNA complex 3 prepared in Example 2.5 was diluted with DMEM medium to an RNA concentration of 0.02 ⁇ g/ ⁇ l. 10 ⁇ l (i.e., 0.2 ⁇ g RNA) was added to each well and cultured for 20 hours.
  • LNPs 1-56 from left to right. Most of the LNPs in LNPs 1-56 were able to transfect RAW264.7 cells. For example, compounds No. 43, No. 38, No. 37, No. 28, No. 27, No. 50, No. 53, No. 23, No. 48, No. 34, No. 29, No. 10, No. 19, No. 52, No. 40, No. 7, No. 42, No. 45, No. 41, No. 25, No. 13, No. 21, No. 56, No. 3, No. 15, No. 4, No. 16, and No. 20 all have good transfection effects.
  • Example 2.7 Delivery of EGFP-mRNA to BMDM cells by LNP-mRNA complex
  • DMEM complete medium with 10ng/ml M-CSF and 75% ethanol.
  • DMEM complete medium with 10ng/ml M-CSF and 75% ethanol.
  • For a 6-well plate add 75% ethanol to the first well (to disinfect the bones); add approximately 1ml of culture medium to the second and third wells (to rinse the bones); and add 3ml of culture medium to the fourth well (to rinse the bones).
  • LNPs 27, 28, 37, 38, 43, and 50 were selected and LNP-EGFP-RNA complexes were prepared according to the method of Example 2.5.
  • the RNA concentration was diluted to 0.02 ⁇ g/ ⁇ l using DMEM medium. 100 ⁇ l (i.e., 2 ⁇ g RNA) was added to each well and cultured for 20 hours.
  • the percentage of F480 + CD11b + EGFP + cells was measured by flow cytometry (FACS), which is the transfection efficiency of the LNP-RNA complex.
  • FACS flow cytometry
  • Example 2.8 LNP-mRNA complex delivery of CAR-CD19/HER2-mRNA to BMDM cells
  • LNP No. 43 was selected to prepare LNP-CAR-CD19/HER2-RNA complex according to the method of Example 2.5.
  • the RNA concentration was diluted to 0.02ug/ul with DMEM medium, 100ul (i.e., 2ug RNA) was added to each well, and cultured for 20 hours.
  • the percentage of F480 + CD11b + CAR-HER2 + cells was detected by flow cytometry (FACS), which was the transfection efficiency of the LNP-mRNA complex.
  • FACS flow cytometry
  • the results were generated by flowjo analysis software, and are shown in Figure 4.
  • the transfection efficiency of LNP No. 43 in BMDM cells was about 14%, which directly demonstrated the successful expression of CAR mRNA and the successful construction of CAR-BMDM cells.
  • Example 2.9 LNP polarizes M0-Raw264.7 cells to M1
  • Raw264.7 cells were seeded and cultured in 6-well plates in DMEM high-glucose medium (HyClone, SH30022.01B) supplemented with 10% FBS, containing penicillin (100 U/ml) and streptomycin (100 ⁇ g/ml), with 1 ⁇ 10 6 cells per well.
  • DMEM high-glucose medium HyClone, SH30022.01B
  • penicillin 100 U/ml
  • streptomycin 100 ⁇ g/ml
  • Example 43 cholesterol, DSPC, and DMG-PEG 2000 is 50:38.5:10:1.5) were prepared according to the method of Example 2.5.
  • the LNP-EGFP-RNA complex was diluted with DMEM culture medium to an RNA concentration of 0.02ug/ul and 0.03ug/ul, and 100ul (i.e., 2ug RNA, 20ug LNP and 3ug RNA, 30ug LNP) was added to each well.
  • LNP without RNA encapsulation was added as a control and cultured for 20 hours; the supernatant was discarded, the cells were washed twice with PBS, the cells were scraped with a cell scraper, and F480 + CD11b was detected by flow cytometry (FACS).
  • Example 2.10 LNP polarizes M0-BMDM cells to M1
  • LNPs No. 27, 28, 37, 38, 43, and 50 were selected to prepare LNP-EGFP-RNA complexes according to the method of Example 2.5.
  • the RNA concentration was diluted to 0.02 ug/ul with DMEM medium, 100 ul (i.e., 2 ug RNA) was added to each well, and cultured for 20 hours.
  • the MFI of F480 + CD11b + cells iNOS-APC was detected by flow cytometry (FACS), which is the polarization effect of different LNPs.
  • FACS flow cytometry
  • the results are shown in Figure 6-1 (flow cytometry scatter plot, generated by Flowjo analysis software) and Figure 6-2.
  • the polarization effect in BMDM is good, among which LNPs No. 37 and 38 are the best.
  • Example 2.11 LNP polarizes M2-BMDM cells to M0 type
  • Example 2 Use LNP No. 43 obtained in Example 2.7 to prepare LNP-CAR CD19-mRNA complex according to the method of Example 2.5, dilute it to an RNA concentration of 0.02ug/ul using DMEM culture medium, add 100ul (i.e., 2ug RNA) to each well, and culture for 20 hours to obtain CAR CD19-BMDM.
  • Luc + Raji cells were added to a six-well plate at an E/T ratio of 20:1, 10:1, 1:1, 1:10, and 1:20, respectively, with a final volume of 1 ml per well.
  • the positive control consisted of Raji cells alone without CAR-BMDM cells, and the volume was made up to 1 ml with culture medium.
  • the negative control consisted of BMDM cells co-incubated with Raji cells. After 24 hours, the supernatant was collected and the cells were lysed using a firefly luciferase reporter gene assay kit (yeasen, 11404ES60). The fluorescence analysis of Raji cells was performed on a microplate reader.
  • the killing ratio was calculated as: (positive control fluorescence intensity - experimental group fluorescence intensity) / (positive control fluorescence intensity - background fluorescence intensity) ⁇ 100%.
  • the results are shown in Figure 8-1 and Figure 8-2 of the in vivo assay.
  • CAR CD19-BMDM was able to kill Raji cells.
  • LNP No. 43 obtained in Example 2.7 was used to prepare LNP-CAR HER2-mRNA complex according to the method of Example 2.5.
  • the RNA concentration was diluted to 0.02 ⁇ g/ ⁇ l with DMEM medium. 100 ⁇ l (i.e., 2 ⁇ g RNA) was added to each well and cultured for 20 hours to obtain CAR HER2-BMDM.
  • the cells were scraped with a scraper and plated in a 96-well plate with 3* 104 cells per well (i.e., 3* 103 CAR-BMDM) and plated overnight.
  • Luc + HER2 + MC38 cells were added to 96-well plates at E/T ratios of 20:1, 10:1, 5:1, 2.5:1, 1:2, 1:10, and 1:20, respectively, with a final volume of 100 ⁇ l per well.
  • the positive control consisted of luc + HER2 + MC38 cells alone without CAR-BMDM cells, and the volume was made up to 100 ⁇ l with culture medium.
  • the negative control was co-incubation of BMDM cells with Raji cells. After 24 h, all cells in the 96-well plate were lysed using a firefly luciferase reporter gene assay kit (yeasen, 11404ES60), and cell fluorescence analysis was performed on a microplate reader.
  • the killing ratio was calculated as: (negative control fluorescence intensity - experimental group fluorescence intensity) / (negative control fluorescence intensity - background fluorescence intensity) ⁇ 100%.
  • the results are shown in Figure 9.
  • CAR HER2-BMDM can kill HER2 + MC38 cells.
  • LNP No. 43 obtained in Example 2.7 was used to prepare LNP-CAR HER2-mRNA and LNP-CAR CD19-mRNA complexes according to the method of Example 2.5.
  • the complexes were diluted with DMEM medium to an RNA concentration of 0.02 ⁇ g/ ⁇ l. 100 ⁇ l (i.e., 2 ⁇ g RNA) was added to each well and cultured for 20 hours to obtain CAR HER2-BMDM and CAR CD19-BMDM.
  • EGFP + HER2 + MC38 cells and EGFP + HER2 + CT26 cells were added to a 6-well plate at an E/T ratio of 1:3. The final volume of each well was 1 ml.
  • the negative controls were CAR CD19-BMDM cells and BMDM cells co-incubated with luc + HER2 + MC38 cells and luc + HER2 + CT26 cells.
  • FACS flow cytometry
  • Example 2.15 In vivo targeting of LNP in wild-type Balb/C mice
  • LNPs 27, 28, 37, 43, and 50 were selected to prepare LNP-CAR HER2-luc-mRNA complexes according to the method of Example 2.4. 20 ⁇ g mRNA/mouse was injected into the tail vein. Six hours later, the bioluminescence intensity distribution in the mice was measured using an IVIS small animal in vivo imaging system, as well as the bioluminescence intensity distribution of the heart, liver, spleen, lung, kidney, and bone marrow after dissection. Before imaging, the mice were intraperitoneally injected with 100 ⁇ L of D-luciferin potassium salt (30 mg/mL, dissolved in PBS). The results are shown in Figures 11-1, 11-2, and 11-3. LNP 37 was primarily distributed in the spleen and liver, with signals also present in the bone marrow. The fluorescence signal intensity of the remaining LNPs was lower than that of LNP 37.
  • Example 2.16 LNP targeting in C57 mice bearing wild-type MC38 tumor cells
  • LNP No. 27, 28, 37, 38, and 43 were selected to prepare LNP-CAR HER2-luc-mRNA complexes according to the method of Example 2.3. 5 ⁇ g mRNA/mouse was injected intratumorally, and the mice were measured by IVIS small animal in vivo imaging system at 6 h, 24 h, and 48 h. In vivo bioluminescence intensity distribution: Before imaging, mice were intraperitoneally injected with 100 ⁇ L of D-luciferin potassium salt (30 mg/mL, dissolved in PBS). As shown in Figures 12-1 and 12-2, LNP No. 37 showed the highest expression and best stability within the tumor.
  • LNP No. 37 was selected and prepared according to the method of Example 2.4. 10 ⁇ g and 20 ⁇ g of mRNA per mouse were injected into the tail vein, respectively. 48 hours later, flow cytometry (FACS) was used to measure the proportion of Td tomato + cells in the spleen and bone marrow, indicating the type of immune cells delivered by LNP No. 37. The results, as shown in Figures 13-1 and 13-2, show that LNP No. 37 can transfect a variety of immune cells in the spleen and bone marrow.
  • FACS flow cytometry
  • Example 2.18 In vivo construction and validation of in situ CAR-myeloid by LNP-mRNA delivery system
  • LNP No. 37 was selected and prepared according to the method of Example 2.4. 20 ⁇ g mRNA/mouse was injected into the tail vein. 24 hours later, orbital blood, bone marrow, and spleen were collected, and the distribution of CAR-HER2 + immune cells was detected by flow cytometry (FACS). The results are shown in Figure 14. LNP No. 37 can generate CAR-immune cells in situ, and they are distributed throughout the body through blood circulation.
  • a lung metastasis model was established by tail vein injection of luc + CT26 tumor cells overexpressing the HER2 antigen to evaluate the in vivo anti-tumor effect of orthotopic CAR-immune cells.
  • Model mice were randomly divided into two groups of five mice each.
  • the IVIS small animal in vivo imaging system was used to measure the bioluminescence intensity of the mouse lungs, which indirectly indicates the severity of the tumor. Before imaging, the mice were injected intraperitoneally with 100 ⁇ L of D-luciferin potassium salt (30 mg/mL, dissolved in PBS).
  • mice The weight of mice was measured every two days, and the weight change curves of the two groups of mice were drawn as shown in Figure 15. The weight of mice in the treatment group was significantly higher than that in the control group.
  • LNP No. 37 was selected to prepare LNP-HER2-mRNA complex according to the method of Example 2.4. 20ug mRNA/mouse was injected into the tail vein and administered once every 4 days for a total of 6 times. Tumor growth was monitored by bioluminescence imaging of the tumor, as shown in Figure 16.
  • Example 2.20 In situ CAR-immune cell therapy for solid tumors
  • a solid tumor model was constructed by subcutaneously inoculating CT26 tumor cells overexpressing the HER2 antigen to evaluate the anti-solid tumor efficacy of in situ CAR-immune cells. Model mice were randomly divided into an experimental group and a control group, with 9 mice in each group.
  • mice The weight and tumor size of mice were measured every two days, and the weight change curves (as shown in Figure 19) and tumor size change curves (as shown in Figure 20) of the two groups of mice were plotted.
  • the length (L) and width (W) of the tumor were measured using a vernier caliper.
  • the tumor size was calculated using the formula: 1/2 ⁇ L ⁇ W 2 .
  • LNP No. 37 was selected and LNP-HER2-mRNA complexes were prepared according to the method of Example 2.4. 20 ⁇ g mRNA/mouse was injected into the tail vein every four days for a total of five doses. On the 10th day of treatment, two mice treated with LNP-CAR mRNA showed tumor regression. On the 13th day of treatment, a significant difference in weight between the two groups was observed (as shown in Figure 20), demonstrating the therapeutic efficacy of this therapy.
  • Example 2.21 Immune cell typing for in situ CAR-immune cell therapy in solid tumors
  • Example 2.22 LNP delivery of circular RNA in vivo
  • LNP No. 43 prepared according to Example 2.2, was dialyzed against ultrapure water in a dialysis bag (3.5K, Thermo Scientific) for at least 3 h at room temperature. The LNP concentration after dialysis was between 0.8 and 1 ⁇ g/ ⁇ l. The LNP was mixed with circular luc RNA LNP at a mass ratio of 10:1 and incubated for 15 min. The mixture was concentrated in a 15 ml 50 kDa ultrafiltration centrifuge tube at 5000 g to obtain the complex for intratumoral injection at a volume of 30-50 ⁇ l/mouse.
  • mice 5 ⁇ g of the complex mRNA/mouse was injected intratumorally.
  • the bioluminescence intensity distribution in the mice was measured using an IVIS small animal in vivo imaging system at 24, 48, and 72 hours. Before imaging, the mice were intraperitoneally injected with 100 ⁇ L of D-luciferin potassium salt (30 mg/mL, dissolved in PBS). The results, as shown in Figure 26, demonstrate that LNP No. 43 can also deliver circular RNA.

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Abstract

一种阳离子脂质化合物、包含其的组合物及应用。所述化合物通式如式（I），包括所述化合物的阳离子脂质化合物，或其药物可用的盐、前药或立体异构体。还涉及一种免疫细胞靶向的脂质纳米颗粒及其筛选方法和用途，具体公开了式(I)的化合物或其药学上可接受的盐、前药或立体异构体在靶向免疫细胞中的用途，同时公开一种体外筛选脂质纳米颗粒的方法和一种筛选适用于体内多种免疫细胞mRNA递送的脂质纳米粒颗粒的方法。

Description

一种新型脂质化合物以及组合物和核酸脂质纳米颗粒制剂及其筛选方法和应用 技术领域
本申请属于生物医药技术领域，具体涉及一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂及其筛选方法和应用，LNP-mRNA递送系统、mRNA及其用途。
背景技术
基因治疗技术是现代生物医药领域研究的热点，利用核酸药物可预防癌症、细菌和病毒感染及治疗具有遗传病因的疾病等。由于核酸药物具有易降解、难以进入细胞等特点，需要借助载体将其封装起来递送至靶细胞，因此，开发安全高效的递送载体就成为基因治疗在临床应用的前提。
脂质纳米颗粒(lipid nanoparticles，LNP)目前是非病毒基因载体领域的研究热点。其作为一类安全高效的核酸药物递送载体，已被证明能将RNA高效地递送到肝脏中，2018年美国FDA批准了全球第一款基于LNP的肝靶向siRNA药物用于治疗遗传性甲状腺素转运蛋白介导的淀粉样变性疾病。而且，目前美国FDA批的两款新冠mRNA疫苗也都是基于LNP开发。然而，LNP核酸递送系统仍面临若干挑战，包括LNP的靶组织主要局限于肝脏以及可能引起的免疫原性。
LNP通常由四种脂质化合物组成，即阳离子脂质、中性脂质、类固醇和PEG-脂质，其中，阳离子脂质的选择对LNP的影响最大，如影响核酸药物的包封率、核酸药物在体内的递送部位与效率以及细胞毒性等。
免疫细胞疗法包括CAR-T、CAR-NK、CAR-DC、CAR-Macrophage等，其中多种免疫细胞疗法尤其是CAR-T疗法在血液肿瘤治疗过程中取得了巨大的成功，但在实体瘤治疗方面单一的免疫细胞疗法仍具有局限性。这是因为肿瘤微环境常常隔离于致密的纤维状肿块中，使免疫细胞难以浸润发挥杀伤作用，同时免疫抑制的微环境也易导致细胞耗竭，而传统的体外形成CRA-免疫细胞再回输入体内的方式往往存在编辑细胞效率低，构建时间长等问题，如何在体内形成多种CAR-免疫细胞，激发肿瘤部位的免疫反应，提高只由单一CAR-免疫细胞所产生的的抗肿瘤效果，是目前存在的问题。
有鉴于此，开发出一种可作为阳离子脂质的新型化合物将具有重要意义。
发明内容
发明要解决的问题
本申请的第一目的是，提供一系列化合物，该化合物可与其他脂质化合物共同制备脂质载体，提升核酸药物在体内的递送效率，，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体。
本申请的第二目的是，提供包含上述化合物的脂质载体。
本申请的第三目的是，提供包含上述化合物或上述脂质载体的核酸脂质纳米粒组合物。
本申请的第四目的是，提供包含上述化合物、或上述脂质载体、或上述核酸脂质纳米粒组合物的药物制剂。
发明的具体技术方案
在一个实施方案中，本申请提供一种通式(I)所示的阳离子脂质化合物，或其药物可用的盐、前药或立体异构体，其中X、Y、Z、G1、G2、G3、G4、G5、G6、L1、L2、L3、L4如本申请或别处所定义。
在一个实施方案中，本申请提供一种纳米颗粒组合物，其包含本申请所提供的化合物以及治疗剂或预防剂。在一个实施方案中，所述治疗剂或预防剂包含至少一种编码抗原或其片段或表位的mRNA。
所属领域的技术人员在考虑以下对特定实施方案的详细描述之后将对本公开的额外特征显而易知。
具体的，本申请采用如下技术方案，
1.一种式(I)的化合物：
或其药学上可接受的盐、前药或立体异构体，其中：
所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；
所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；
Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；
x是0、1或2；
所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；
所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；
Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；
i是0、1或2；
所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；
所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；
其中，Re和Rf为任选地取代的C1-C12亚烷基；
G7为-NRg-、-(3-7元饱和环亚烷烃)-、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；
Rg为任选地取代的C1-C12亚烷基；
所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
2.根据项1所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A)所示的结构：
其中，G1、G2、G3、G4、G5、G6、L1、L2、L3、L4、X和Y如项1中所定义；
G8为任选地取代的C1-C12亚烷基。
3.根据项1所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B)所示的结构：
其中，G1、G2、G3、G4、G5、G6、G7、L1、L2、L3、L4、Re、Rf、X和Y如项1中所定义。
4.根据项1至3中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G1和G2是未被取代的C2-C4亚烷基。
5.根据项1至4中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中L1和L2是-C(＝O)O-。
6.根据项1至5中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G3和G4为键。
7.根据项1至5中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G3和G4为未被取代的C2-C4亚烷基。
8.根据项1至6中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中L3和L4为键。
9.根据项1-5、7中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中L3和L4是-OC(＝O)O-。
10.根据项1至9中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，G5和G6为任选地取代的C4-C16直链烯基。
11.根据项2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-1)所示的结构：
其中，m为1或3，n为0或1，G5和G6的定义如项10所定义，G8为项2所定义，G9和G10为任选地取代的C1-C5直链烷烃。
12.根据项2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-2)所示的结构：
其中，m为1或3，n为0或1，G5和G6的定义如项10所定义。
13.根据项2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-3)所示的结构：
其中，m为1或3，n为0或1，G5和G6的定义如项10所定义。
14.根据项2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特 征在于，所述化合物具有式(I-A-4)所示的结构：
其中，G1、G2、G3、G4、G5、G6、L1、L2、L3、L4和Y的定义如项1中所定义；G8为任选地取代的C1-C12亚烷基。
15.根据项2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，所述化合物具有式(I-A-5)所示的结构：
其中，m为1或3，n为0或1，Y、G5和G6的定义如项1中所定义；G8为任选地取代的C1-C12亚烷基。
16.根据项2、4-10中任一项所述的用途，或其药学上可接受的盐、前药或立体异构体，所述化合物具有式(I-A-6)所示的结构：
其中，m为1或3，n为0或1，Y、G5和G6的定义如项1中所定义。
17.根据项3-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B-1)所示的结构：
其中，m为1或3，n为0或1，G5和G6的定义如项10所定义。
18.根据项3-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B-2)所示的结构：
其中，m为1或3，n为0或1，G5和G6的定义如项10所定义。
19.根据项3-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B-3)所示的结构：
其中，m为1或3，n为0或1，G5和G6的定义如项10所定义。
20.根据项3-10中任一项所述的用途，或其药学上可接受的盐、前药或立体异构体，所述化合物具有式(I-B-4)所示的结构：
其中，G1、G2、G3、G4、G5、G6、G7、L1、L2、L3、L4、Re和Rf如项1中所定义。
21.根据项2、4-11中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G8为任选地取代的C2-C4亚烷基。
22.根据项2、4-11中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G9或G10或两者具有以下结构之一：甲基、乙基、2-羟基乙基。
23.根据项1至22中任一项所述的化合物，其中G5或G6或两者具有以下结构之一：
24.根据项1至23中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其为如表1所示的化合物。
25.一种组合物，其包含：治疗剂或预防剂；以及用于递送所述治疗剂或预防剂的载体，其中，所述载体包括阳离子脂质，所述阳离子脂质包括项1至24中任一项所述的式(I)所示的化合物、或其药物可用的盐中的一种或多种。
26.根据项25所述的组合物，其中所述治疗剂或预防剂选自核酸分子、小分子化合物、多肽或蛋白质中的一种或多种，优选，其中所述核酸分子选自单链DNA、双链DNA、短异构体、agomir、antagomir、反义分子、小干扰RNA(siRNA)、不对称干扰RNA(aiRNA)、microRNA(miRNA)、Dicersubstrate RNA(dsRNA)、小发夹RNA(shRNA)、转移RNA(tRNA)、信使RNA(mRNA)、锁核酸(LNA)、肽核酸(PNA)或吗啉环寡聚核苷酸中的一种或多种。
27.根据项26所述的组合物，所述治疗剂或预防剂包含至少一种编码抗原或其片段或表位的mRNA优选，所述的mRNA是单顺反子mRNA或多顺反子mRNA。
28.根据项27所述的组合物，所述的抗原是病原性抗原。
29.根据项26所述的组合物，所述mRNA包含一种或多种功能性核苷酸类似物，所述功能性核苷酸类似物选自假尿嘧啶核苷、1-甲基-假尿嘧啶核苷或5-甲基胞嘧啶中的一种或多种。
30.根据项25，所述小分子化合物选自抗肿瘤药、抗感染药、局部麻醉药、抗抑郁药、抗惊厥药、抗生素/抗菌剂、抗真菌药、抗寄生虫药、激素、激素拮抗剂、免疫调节剂、神经递质拮抗剂、抗青光眼剂、麻醉剂或成像剂中的一种或多种。
31.根据项25所述的组合物，所述载体与所述治疗或预防剂的质量比为5：1～50：1。
32.根据项25所述的组合物，所述组合物为纳米颗粒制剂，所述纳米颗粒制剂的平均尺寸为10～500nm；或者；所述纳米颗粒的pKa为4.5～8.5。
33.根据项25至32中任一项所述的组合物，其中，所述载体进一步包含或一种或多种中性脂质。
34.根据项33所述的组合物，其中所述中性脂质为选自磷脂酰胆碱、磷脂酰乙醇胺、鞘磷脂、神经酰胺、甾醇及其衍生物中的一种或多种。
35.根据项25至34中任一项所述的组合物，其中阳离子脂质与所述中性脂质的摩尔比为100：1～5:1。
36.根据项25至32中任一项所述的组合物，其进一步包含类固醇，优选，所述类固醇为选自胆固醇、非甾醇、谷固醇、麦角固醇、菜油甾醇、豆甾醇、芸苔甾醇、番茄碱、番茄碱、熊果酸、α-生育酚、皮质类固醇中的一种或多种。
37.根据项25至36中任一项所述的组合物，其中阳离子脂质与所述类固醇的摩尔比为2:1～4:1。
38.根据项25至36中任一项所述的组合物，其中所述组合物进一步包含一种或多种能够与聚合物结合的脂质，优选，所述能够与聚合物结合的脂质为选自PEG修饰的磷脂酰乙醇胺、PEG修饰的磷脂酸、PEG修饰的神经酰胺、PEG修饰的二烷基胺、PEG修饰的二酰基甘油或PEG修饰的二烷基甘油中的一种或多种，进一步优选，其中所述阳离子脂质与所述能够与聚合物结合的脂质的摩尔比为100:1～20:1。
39.根据项25至36中任一项所述的组合物，所述载体还包括中性脂质、结构脂质以及聚合物共轭脂质，所述阳离子脂质、所述中性脂质、所述类固醇脂质、以及所述聚合物共轭脂质的摩尔比为(15～70)：(1～15):(15～55):(0～3)。
40.根据项25所述的组合物，其特征在于，所述的组合物还包括药物可用的赋形剂，优选，所述的赋形剂包括药物可用的稀释剂。
41.一种如项1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或项25至40中任一项所述的组合物在在制备药物中的应用，优选所述药物为选自基因药物、核酸疫苗、小分子药物、多肽或蛋白质药物中的任一种。
42.一种如项1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或项25至40中任一项所述的组合物在靶向免疫细胞中的用途。
43.一种如项1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或项25至40中任一项所述的组合物在制备靶向免疫细胞的药物中的用途。
44.根据项42或43所述的用途，其中，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞。
45.一种如项1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或项25至40中任一项所述的组合物在促进细胞极化中的用途。
46.一种如项1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或项25至40中任一项所述的组合物在制备促进免疫细胞极化的药物中的用途。
47.根据项45或46所述的用途，其中，所述细胞极化为由M0型向M1型极化。
48.根据项45或46所述的用途，其中，所述细胞极化为由M2型向M0型极化。
49.根据项45或46所述的用途，其中，所述细胞为巨噬细胞。
50.一种体外筛选脂质纳米颗粒的方法，其包括：
在巨噬细胞细胞系中进行第一次筛选，获得可以转染巨噬细胞细胞系的脂质纳米颗粒；
在获得的脂质纳米粒颗粒中选择FLuc荧光信号强度高于10000RLUs的脂质纳米粒颗粒在骨髓来源的原代巨噬细胞中进行第二次筛选；
第二次筛选后获得目标脂质纳米颗粒。
51.根据项50所述的方法，其中，所述巨噬细胞细胞系为Raw264.7细胞系。
52.一种筛选适用于体内免疫细胞mRNA递送的脂质纳米粒颗粒的方法，其包括：
将包裹携带报告基因的CAR-mRNA的脂质纳米粒颗粒经尾静脉注射入野生型小鼠，筛选获得在给定器官有表达且表达比例高于80％的第一脂质纳米粒颗粒；
任选的，将筛选获得第一脂质纳米粒颗粒包裹携带报告基因的CAR-mRNA，瘤内注射荷瘤小鼠，筛选获得只在肿瘤部位表达，其他器官不表达，且稳定表达24～48h的第二脂质纳米粒颗粒；
将筛选获得第一或第二脂质纳米粒颗粒经尾静脉注射入Cre报告基因小鼠，筛选获得在免疫细胞具有Td tomato+细胞的目标脂质纳米粒颗粒。
53.根据项50所述的方法，其中，所述给定器官选自脾脏或骨髓。
54.根据项50所述的方法，其中，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞中的任意一种。
55.根据项50-54中任一项所述的方法，其中，所述目标脂质纳米颗粒为项1-24中涉及的式(I)的化合物或其药学上可接受的盐、前药或立体异构体所制备得到。
发明效果
本申请的阳离子脂质化合物及其组合物可用于递送核酸药物或小分子药物，丰富了阳离子脂质化合物种类，对核酸预防剂及治疗剂的发展和应用具有重要的意义。
巨噬细胞构成肿瘤微环境中最大的免疫细胞群，并具有穿透实体瘤和催化免疫反应的能力，为了筛选体内形成多种CAR-免疫细胞的LNP(脂质纳米颗粒)，本申请首先通过体外巨噬细胞筛选，进一步的体内筛选，得到原位构建多种CAR-免疫细胞的LNP。
1、本申请提供的体外巨噬细胞mRNA递送的LNP筛选方式解决了直接在原代巨噬细胞筛选导致的原代细胞用量高、提取原代细胞时间长的问题。
2、本申请提供的体内免疫细胞mRNA递送的LNP筛选方式，过程简便，构建原位CAR-免疫细胞治疗效果好。
3、本申请提供的LNP-mRNA复合物可以将mRNA递送至巨噬细胞，转染时间短，转染方式简便，转染率为30.2％，为过继性免疫治疗的细胞编辑方式提供参考。
4、本申请提供的LNP-mRNA复合物可以递送环状mRNA，并可稳定表达72h。
5、本申请提供的一些LNP可以将未极化的M0型巨噬细胞极化成为M1型促炎表型。
6、本申请提供的一些LNP可以将抗炎促肿瘤的M2型巨噬细胞极化成为M0型。
7、本申请提供的一些LNP可以将mRNA递送至脾脏和骨髓，产生多种CAR-免疫细胞，包括T细胞、巨噬细胞、DC细胞、NK细胞。
8、本申请提供的体内原位CAR-细胞在肺转移和实体瘤模型中治疗效果良好。
9、本申请提供的LNP制备方法简单，重复性好，递送mRNA可在体内稳定表达48h，具有良好的应用前景。
附图说明
附图用于更好地理解本申请，不构成对本申请的不当限定。其中：
图1是实施例2.1中的筛选流程图；
图2是实施例2.6中的Raw264.7细胞上LNP的筛选结果图；
图3-1是实施例2.7中的BMDM细胞上通过流式细胞仪的LNP的筛选结果图；
图3-2是实施例2.7中的BMDM细胞上LNP的筛选转染效率结果图；
图4是实施例2.8中的BMDM细胞上43号LNP转染CAR-HER2 mRNA的结果图；
图5-1是实施例2.9中的Raw264.7细胞上不同转染效率的LNP(43、43-1)以及包裹不同质量RNA对巨噬细胞极化的影响(荧光表示)；
图5-2是实施例2.9中的Raw264.7细胞上不同转染效率的LNP(43、43-1)以及包裹不同质量RNA对巨噬细胞极化的影响(iNOS表示)；
图6-1是实施例2.10中的BMDM细胞上不同LNP的极化效果；
图6-2是实施例2.10中的BMDM细胞上不同LNP的极化效果(统计结果)；
图7是实施例2.11中37和43号LNP将M2-BMDM细胞极化成为M0型；
图8-1是实施例2.12中CAR CD19-BMDM细胞杀伤Raji细胞结果图(杀伤比例)；
图8-2是实施例2.12中CAR CD19-BMDM细胞杀伤Raji细胞结果图(荧光分析检测)；
图9是实施例2.13中CAR HER2-BMDM细胞杀伤HER2+MC38细胞结果图；
图10是实施例2.14中CAR HER2-BMDM细胞吞噬HER2+MC38细胞和HER2+CT26细胞结果图；
图11-1是实施例2.15中几种LNP在野生型B/C小鼠体内生物分布情况(活体)；
图11-2是实施例2.15中几种LNP在野生型B/C小鼠体内生物分布情况(解刨后)；
图11-3是实施例2.15中几种LNP在野生型B/C小鼠体内生物分布情况(统计图)；
图12-1是实施例2.16中多种LNP在野生型MC38肿瘤细胞荷瘤C57小鼠体内随时间信号变化(活体)；
图12-2是实施例2.16中多种LNP在野生型MC38肿瘤细胞荷瘤C57小鼠体内随时间信号变化；
图13-1是实施例2.17中Cre转基因报告小鼠骨髓免疫细胞特异性检测结果；
图13-2是实施例2.17中Cre转基因报告小鼠脾脏免疫细胞特异性检测结果；
图14是实施例2.18中外周血中HER2+细胞分布；
图15是实施例2.19中对照组(UT)和治疗组(Treated)小鼠体重变化曲线；
图16是实施例2.19中对照组(UT)和治疗组(Treated)小鼠IVIS成像结果图；
图17是实施例2.19中对照组(UT)和治疗组(Treated)小鼠IVIS检测肺部荧光信号量化图；
图18是实施例2.19中对照组(UT)和治疗组(Treated)小鼠生存曲线图；
图19是实施例2.20中对照组(UT)和治疗组(Treated)小鼠体重变化曲线；
图20是实施例2.20中对照组(UT)和治疗组(Treated)小鼠肿瘤大小变化曲线；
图21是实施例2.20中对照组(UT)和治疗组(Treated)小鼠AST、ALT检测结果图；
图22是实施例2.21中对照组(UT)和治疗组(Treated)小鼠肿瘤免疫组化分析。
图23是实施例2.21中对照组(UT)和治疗组(Treated)小鼠肿瘤部位M2型巨噬细胞流式分析。
图24是实施例2.21中对照组(UT)和治疗组(Treated)小鼠肿瘤部位CD4+细胞流式分析。
图25是实施例2.21中对照组(UT)和治疗组(Treated)小鼠肿瘤部位CD8+细胞流式分析。
图26是实施例2.22中LNP递送环状Luc mRNA 24h、48h、72h肿瘤部位IVIS成像结果图。
具体实施方式
术语
除非另有描述，否则本申请中使用的所有技术和科学术语具有与所属领域的技术人员通常所理解相同的含义。出于解释本说明书的目的，将应用以下术语描述，并且在适当时，以单数形式使用的术语还将包括复数形式，反之亦然。所有专利、申请、公布的申请和其他出版物均以全文引用的方式并入。如果所阐述的关于术语的任何描述与以引用的方式并入本申请中的任何文件相冲突，则以下文阐述的术语描述为准。
除非上下文另外需要，在本说明书和权利要求书中，词语“包括(comprise)”及其变形，如“包含”和“含有”，以开放且包括的含义解释，即，为“包括，但不限于”。
如本申请所使用且除非另有说明，否则术语“脂质”是指一组有机化合物，其包括但不限于脂肪酸酯，并且一般以难溶于水但可溶于许多非极性有机溶剂中为特征。尽管脂质一般具有弱水溶性，但是某些类别的脂质(例如经极性基团改性的脂质，例如DMG-PEG2000)具有有限的水溶性且在某些条件下可溶于水。已知的脂质类型包括生物分子，如脂肪酸、蜡、固醇、脂溶性维生素、甘油单酸酯、甘油二酸酯、甘油三酸酯和磷脂。脂质可分为至少三类：(1)“简单脂质”，包括脂肪和油，以及蜡；(2)“化合物脂质”，包括磷脂和糖脂(例如DMPEPEG2000)；和(3)“衍生脂质”，如类固醇。此外，如本申请所使用，脂质还包括类脂质化合物。术语“类脂质化合物”又简称为“类脂质”，是指脂质样化合物(例如具有脂质样物理性质的两亲性化合物)。
如本申请所使用且除非另有说明，否则术语“脂质纳米颗粒”或“LNP”是指具有至少一个纳米(nm)级尺寸(例如1至1,000nm)的颗粒，其含有一种或多种类型的脂质分子。本申请所提供的LNP可进一步含有至少一种非脂质有效负载分子(例如一种或多种核酸分子)或小分子药物。在一些实施方案中，LNP包含部分或完全包封在脂质壳内的非脂质有效负载分子。其中有效负载是带负电分子(例如编码病毒蛋白的mRNA)，并且LNP的脂质组分包含至少一种阳离子脂质。不受理论束缚，预期阳离子脂质可与带负电的有效负载分子相互作用，并在LNP形成期间促进有效负载并入和/或包封至LNP中。可形成如本申请所提供的LNP的一部分的其他脂质包括但不限于中性脂质和带电脂质，如类固醇或其类似物、聚合物结合的脂质和各种两性离子性脂质。
如本申请所使用且除非另有说明，否则术语：“阳离子脂质”指能够带正电的脂质。示例性的阳离子脂质包括一种或多种带有正电荷的胺基团。优选的阳离子脂质是可电离的，以便它们可以根据pH 值以带正电的形式或中性形式存在。阳离子脂质的电离影响脂质纳米颗粒在不同pH条件下的表面电荷。这种电荷状态可以影响血浆蛋白吸收、血液清除和组织分布(Semple,S.C.等人，Adv Drug Deliv Rev 32:3-17(1998))以及形成核内体溶解(endosomolytic)非双层结构的能力(Hafez,I.M.等人，Gene Ther 8:1188-1196(2001))，对于核酸的细胞内递送是至关重要的。
如本申请所使用且除非另有说明，否则术语“类固醇”为包含以下碳骨架的化合物：
类固醇的非限定实例包含胆固醇等。
如本申请所使用且除非另有说明，否则术语“中性脂质”涵盖在所选pH值下或在所选pH值范围内以不带电形式或以中性两性离子形式存在的任何脂质分子。在一些实施方案中，所选的有用pH值或范围对应于预定脂质用途的环境中的pH条件，如生理pH值。作为非限制性实例，可结合本公开使用的中性脂质包括但不限于磷脂酰胆碱，如1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱(DSPC)、1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱(DPPC)、1,2-二肉豆蔻酰基-sn-甘油-3-磷酸胆碱(DMPC)、1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱(POPC)、1,2-二油酰基-sn-甘油-3-磷酸胆碱(DOPC)；磷脂酰乙醇胺，如1,2-二油酰基-sn-甘油-3-磷酸乙醇胺(DOPE)、2-((2,3-双(油酰氧基)丙基))二甲基铵基)乙基磷酸氢盐(DOCP)；鞘磷脂(SM)；神经酰胺；类固醇，如固醇、甾醇和其衍生物。本申请所提供的中性脂质可为合成的或者衍生自天然来源或化合物(自其分离或改性)。
如本申请所使用且除非另有说明，否则术语“烷基”是指仅由碳和氢原子组成的饱和直链或支链烃链基团。在一个实施方案中，烷基具有例如一至二十四个碳原子(C1-C24烷基)、四至二十个碳原子(C4-C20烷基)、六至十六个碳原子(C6-C16烷基)、六至九个碳原子(C6-C9烷基)、一至十五个碳原子(C1-C15烷基)、一至十二个碳原子(C1-C12烷基)、一至八个碳原子(C1-C8烷基)或一至六个碳原子(C1-C6烷基)且其通过单键连接至分子其余部分。烷基的实例包括但不限于甲基、乙基、正丙基、1-甲基乙基(异丙基)、正丁基、正戊基、1,1-二甲基乙基(叔丁基)、3-甲基己基、2-甲基己基等。除非另有说明，否则烷基任选地经取代。
如本申请所使用且除非另有说明，否则术语“烯基”是指仅由碳和氢原子组成的直链或支链烃链基团，其含有一个或多个碳-碳双键。所属领域的技术人员应了解，术语“烯基”还包含具有“顺式”和“反式”构型，或者具有“E”和“Z”构型的基团。在一个实施方案中，烯基具有例如二至二十四个碳原子(C2-C24烯基)、四至二十个碳原子(C4-C20烯基)、六至十六个碳原子(C6-C16烯基)、六至九个碳原子(C6-C9烯基)、二至十五个碳原子(C2-C15烯基)、二至十二个碳原子(C2-C12烯基)、二至八个碳原子(C2-C8烯基)或二至六个碳原子(C2-C6烯基)且其通过单键连接至分子其余部分。烯基的实例包括但不限于乙烯基、丙-1-烯基、丁-1-烯基、戊-1-烯基、戊-1,4-二烯基等。除非另有说明，否则烯基任选地经取代。
如本申请所使用且除非另有说明，否则术语“炔基”是指仅由碳和氢原子组成的直链或支链烃链基团，其含有一个或多个碳-碳三键。在一个实施方案中，炔基具有例如二至二十四个碳原子(C2-C24炔基)、四至二十个碳原子(C4-C20炔基)、六至十六个碳原子(C6-C16炔基)、六至九个碳原子(C6-C9炔基)、二至十五个碳原子(C2-C15炔基)、二至十二个碳原子(C2-C12炔基)、二至八个碳原子(C2-C8炔基)或二至六个碳原子(C2-C6炔基)且其通过单键连接至分子其余部分。炔基的实例包括但不限于乙炔基、丙炔基、丁炔基、戊炔基等。除非另有说明，否则炔基任选地经取代。
如本申请所使用且除非另有说明，否则术语“成环”是指所述分子内部或分子之间局部或全部连接，形成环状分子结构，连接点可由包括但不限于一个C或N或几个C或N进行，成环的分子结构可以是饱和的也可以是不饱和的。除非另有说明，否则成环的分子部分任选地经取代。
当本申请所描述的基团被称为“取代”时，其可经一个或多个任何适当的取代基取代。取代基的说明性实例包括但不限于在本申请所提供的示例性化合物和实施方案中发现的取代基，以及：卤素原子，如F、Cl、Br或I；氰基；氧代(＝O)；羟基(-OH)；烷基；烯基；炔基；环烷基；芳基；-(C＝O)OR’；-O(C＝O)R’；-C(＝O)R’；-OR’；-S(O)xR’；-S-SR’；-C(＝O)SR’；-SC(＝O)R’；-NR’R’；-NR’C(＝O)R’；-C(＝O)NR’R’；-NR’C(＝O)NR’R’；-OC(＝O)NR’R’；-NR’C(＝O)OR’；-NR’S(O)xNR’R’；-NR’S(O)xR’； 和-S(O)xNR’R’，其中：R’在每次出现时独立地为H、C1-C15烷基或环烷基，并且x是0、1或2。
如本申请所使用且除非另有说明，否则术语“任选地选用的”或“任选地”(例如任选地经取代)意指随后描述的事件或情况可能会发生或可能不会发生，并且该描述包括所述事件或情况发生的情况和其不发生的情况。举例来说，“任选地经取代的烷基”意指烷基可经取代或可不经取代，并且该描述包括经取代的烷基和不具有取代的烷基两者。
术语“前体药物”是指在适用于患者后能够直接或间接地提供本申请的化合物或核酸药物的衍生物。组合物的前药可通过修饰化合物或核酸(DNA、ASO、siRNA、mRNA、tRNA)中存在的官能基来制备，其方式是使得修饰可在常规操作中或在活体内裂解而得到母体化合物或核酸。特别优选的前药是在施用于患者时可以提高本申请的组合物的生物利用度的化合物和核酸药物(例如，更易吸收入血)，或者促进母体化合物向作用位点(例如，淋巴系统)递送的化合物和核酸药物。除非另外指出，本申请的化合物的所有前药形式都在本申请的范围之内，且各种前药形式是本领域熟知的。
如本申请所使用且除非另有说明，否则术语“药学上可接受的盐”包括酸加成盐和碱加成盐两者。
药学上可接受的酸加成盐的实例包括但不限于盐酸、氢溴酸、硫酸、硝酸、磷酸等；以及有机酸，例如但不限于乙酸、2,2-二氯乙酸、己二酸、褐藻酸、抗坏血酸、天冬氨酸、苯磺酸、苯甲酸、4-乙酰胺基苯甲酸、樟脑酸、樟脑-10-磺酸、癸酸、己酸、辛酸、碳酸、肉桂酸、柠檬酸、环拉酸(cyclamic acid)、十二烷基硫酸、乙烷-1,2-二磺酸、乙烷磺酸、2-羟基乙烷磺酸、甲酸、富马酸、半乳糖二酸、龙胆酸、葡庚糖酸、葡糖酸、葡糖醛酸、谷氨酸、戊二酸、2-氧代戊二酸、甘油磷酸、乙醇酸、马尿酸、异丁酸、乳酸、乳糖酸、月桂酸、马来酸、苹果酸、丙二酸、扁桃酸、甲烷磺酸、粘液酸、萘-1,5-二磺酸、萘-2-磺酸、1-羟基-2-萘甲酸、烟碱酸、油酸、乳清酸、草酸、棕榈酸、帕莫酸(pamoic acid)、丙酸、焦谷氨酸、丙酮酸、水杨酸、4-氨基水杨酸、癸二酸、硬脂酸、琥珀酸、酒石酸、硫氰酸、对甲苯磺酸、三氟乙酸、十一碳烯酸等。
药学上可接受的碱加成盐的实例包括但不限于通过将无机碱或有机碱添加至游离酸化合物而制备的盐。衍生自无机碱的盐包括但不限于钠、钾、锂、铵、钙、镁、铁、锌、铜、锰、铝盐等。在一个实施方案中，无机盐是铵盐、钠盐、钾盐、钙盐和镁盐。衍生自有机碱的盐包括但不限于以下的盐：伯胺、仲胺和叔胺；经取代胺，包括天然存在的经取代胺；环胺和碱性离子交换树脂，如氨、异丙胺、三甲胺、二乙胺、三乙胺、三丙胺、二乙醇胺、乙醇胺、丹醇(deanol)、2-二甲基氨基乙醇、2-二乙基氨基乙醇、二环己胺、赖氨酸、精氨酸、组氨酸、咖啡因、普鲁卡因(procaine)、哈胺(hydrabamine)、胆碱、甜菜碱、苯乙芐胺(benethamine)、芐星(benzathine)、乙二胺、葡糖胺、甲基葡糖胺、可可碱(theobromine)、三乙醇胺、氨基丁三醇、嘌呤、哌嗪、哌啶、N-乙基哌啶、聚胺树脂等。
本申请所提供的化合物可含有一个或多个不对称中心，且因此可产生对映异构体、非对映异构体和其他立体异构形式，所述形式可根据绝对立体化学定义为(R)-或(S)-或对于氨基酸可定义为(D)-或(L)-。除非另有说明，否则本申请所提供的化合物意图包括所有此类可能的异构体，以及其外消旋和光学纯形式。当本申请所述化合物含有烯属双键或其他几何不对称中心时，除非另有说明，否则所述化合物意欲包括E和Z几何异构体。同样，还意欲包括所有互变异构形式。
如本申请所使用且除非另有说明，否则术语“异构体”是指具有相同分子式的不同化合物。“立体异构体”是仅原子在空间中的排列方式不同的异构体。“阻转异构体”是由绕单键的受阻旋转得到的立体异构体。“对映异构体”是一对互为不可重叠的镜像的立体异构体。一对对映异构体的任何比例的混合物可称为“外消旋”混合物。“非对映异构体”是具有至少两个不对称原子但不互为镜像的立体异构体。
“立体异构体”还可包括E和Z异构体或其混合物，以及顺式和反式异构体或其混合物。在某些实施方案中，本申请所述的化合物分离为E或Z异构体。在其他实施方案中，本申请所述的化合物是E和Z异构体的混合物。
术语“核酸”是指任何长度的核苷酸聚合物，并且包括例如DNA和RNA。核苷酸可为脱氧核糖核苷酸、核糖核苷酸、经修饰的核苷酸或碱基和/或其类似物，或可通过DNA或RNA聚合酶或通过合成反应并入聚合物中的任何底物。核酸可为单股或双股形式。如本申请所使用且除非另有说明，否则“核酸”还包括核酸模拟物，如锁核酸(LNA)、肽核酸(PNA)和吗啉核酸。如本申请所使用，“寡核苷酸”是指短的合成聚核苷酸，其长度一般但未必少于约200个核苷酸。术语“寡核苷酸”与“聚核苷酸”并非互相排斥。以上关于聚核苷酸的描述同样且完全适用于寡核苷酸。除非另有说明，否则本申请所公开的任何单股聚核苷酸序列的左手端为5′端；双股聚核苷酸序列的左手方向称为5′方向。新生RNA转 录物的5′至3′添加方向称为转录方向；DNA股上具有与RNA转录物相同的序列且相对于RNA转录物的5′端而位于5′端的序列区域称为“上游序列”；DNA股上具有与RNA转录物相同的序列且相对于RNA转录物的3′端而位于3′端的序列区域称为“下游序列”。
“分离的核酸”是指与天然地伴随天然序列的其他基因组DNA序列以及蛋白质或复合物(如核糖体和聚合酶)基本上分离的核酸，例如RNA、DNA或混合核酸。“分离”的核酸分子是与存在于核酸分子的天然来源中的其他核酸分子分离的核酸分子。此外，当通过重组技术制造时，“分离”的核酸分子，如mRNA分子，可基本上不含其他细胞材料或培养基，或者当化学合成时，其可基本上不含化学前体或其他化学品。在特定实施方案中，本申请所述的编码抗原的一种或多种核酸分子是分离或纯化的。该术语包括已自其天然存在的环境移除的核酸序列，并且包括重组或克隆的DNA或RNA分离物以及化学合成的类似物或由异源系统生物合成的类似物。基本上纯的分子可包括分子的分离形式。
术语“编码核酸”或其语法等效物当用于指核酸分子时包括：(a)处于天然状态或通过所属领域的技术人员熟知的方法操作时可转录产生mRNA且接着转译成肽和/或多肽的核酸分子；和(b)mRNA分子本身。反义股是此类核酸分子的互补序列，并且可由其推断出编码序列。术语“编码区”是指编码核酸序列中转译成肽或多肽的部分。术语“非转译区”或“UTR”是指编码核酸中不转译成肽或多肽的部分。取决于UTR相对于核酸分子的编码区的取向，UTR如果位于编码区5′端，则称为5′-UTR，并且UTR如果位于编码区3′端，则称为3′-UTR。
如本申请所使用，术语“mRNA”是指包含一个或多个开放阅读框(ORF)的信使RNA分子，其可经具有所述mRNA的细胞或生物体转译以产生一种或多种肽或蛋白质产物。含有一个或多个ORF的区域称为mRNA分子的编码区。在某些实施方案中，mRNA分子进一步包含一个或多个非转译区(UTR)。
在某些实施方案中，mRNA是仅包含一个ORF的单顺反子mRNA。在某些实施方案中，单顺反子mRNA编码包含选定抗原(例如致病性抗原或肿瘤相关抗原)的至少一个表位的肽或蛋白质。在其他实施方案中，mRNA是包含两个或更多个ORF的多顺反子mRNA。在某些实施方案中，多顺反子mRNA编码可彼此相同或不同的两种或更多种肽或蛋白质。在某些实施方案中，由多顺反子mRNA编码的每种肽或蛋白质包含选定抗原的至少一个表位。在某些实施方案中，由多顺反子mRNA编码的不同肽或蛋白质各自包含不同抗原的至少一个表位。在本申请所述实施方案中的任一个中，所述至少一个表位可为抗原的至少2个、至少3个、至少4个、至少5个、至少6个、至少7个、至少8个、至少9个或至少10个表位。
术语“核碱基”涵盖嘌呤和嘧啶，包括天然化合物腺嘌呤、胸腺嘧啶、鸟嘌呤、胞嘧啶、尿嘧啶、肌苷以及其天然或合成类似物或衍生物。
如本申请所使用，术语“功能性核苷酸类似物”是指经典核苷酸A、G、C、U或T的经修饰型式，所述型式(a)保留相应经典核苷酸的碱基配对特性，并且(b)含有至少一种对相应天然核苷酸的(i)核碱基、(ii)糖基、(iii)磷酸酯基或(iv)(i)至(iii)的任何组合的化学修饰。如本申请所使用，碱基配对不仅涵盖经典沃森-克里克(Watson-Crick)腺嘌呤-胸腺嘧啶、腺嘌呤-尿嘧啶或鸟嘌呤-胞嘧啶碱基对，而且还涵盖在经典核苷酸与功能性核苷酸类似物之间或在一对功能性核苷酸类似物之间形成的碱基对，其中氢键供体与氢键受体的布置允许在经修饰的核碱基与经典核碱基之间或在两个互补的经修饰核碱基结构之间形成氢键。举例来说，鸟苷(G)的功能性类似物保留与胞嘧啶(C)或胞嘧啶的功能性类似物碱基配对的能力。此类非经典碱基配对的一个实例是经修饰核苷酸肌苷与腺嘌呤、胞嘧啶或尿嘧啶之间的碱基配对。如本申请所述，功能性核苷酸类似物可为天然存在或非天然存在的。因此，含有功能性核苷酸类似物的核酸分子可具有至少一个经修饰的核碱基、糖基和/或核苷间键联。本申请提供对核酸分子的核碱基、糖基或核苷间键联的示例性化学修饰。
如本申请所使用，术语“转译强化子元件”、“TEE”和“转译强化子”是指核酸分子中用于促进核酸的编码序列转译成蛋白质或肽产物，如经由帽依赖性或非帽依赖性转译而转译。成蛋白质或肽产物的区域。TEE典型地位于核酸分子(例如mRNA)的UTR区，并增强位于上游或下游的编码序列的转译水平。举例来说，核酸分子的5'-UTR中的TEE可位于核酸分子的启动子与起始密码子之间。各种TEE序列是此项技术中已知的(Wellensiek等人，Genome-wideprofiling of human cap-independent translation-enhancing elements,NatureMethods,2013年8月；10(8):747-750；Chappell等人，PNAS,2004年6月29日,101(26)9590-9594)。已知一些TEE在多个物种中是保守的(Pánek等人，Nucleic Acids Research,第41卷,第16期,2013年9月1日,第7625-7634页)。
如本申请所使用，术语“肽”是指含有二至五十(2-50)个经一个或多个共价肽键连接的氨基酸残基的聚合物。所述术语适用于天然存在的氨基酸聚合物以及一个或多个氨基酸残基是非天然存在的氨基酸(例如氨基酸类似物或非天然氨基酸)的氨基酸聚合物。
术语“多肽”与“蛋白质”在本申请中可互换使用，指具有超过五十(50)个由共价肽键连接的氨基酸残基的聚合物。也就是说，针对多肽的描述同样适用于针对蛋白质的描述，反之亦然。所述术语适用于天然存在的氨基酸聚合物以及一个或多个氨基酸残基是非天然存在的氨基酸(例如氨基酸类似物)的氨基酸聚合物。如本申请所使用，所述术语涵盖任何长度的氨基酸链，包括全长蛋白质(例如抗原)。
术语“抗原”是指能够被受试者的免疫系统(包括适应性免疫系统)识别的物质，并且在受试者与抗原接触之后能够触发免疫反应(包括抗原特异性免疫反应)。在某些实施方案中，抗原是与患病细胞，如感染病原体的细胞或赘生性细胞相关的蛋白质(例如肿瘤相关抗原(TAA))。
“表位”是抗原分子表面上与单个抗体分子结合的位点，如抗原表面上能够结合至抗体的一个或多个抗原结合区的局部区域，并且其在动物体内，如在哺乳动物体内(例如人体内)具有抗原或免疫原性活性，能够引起免疫反应。具有免疫原性活性的表位是多肽的在动物体内引起抗体反应的部分。具有抗原活性的表位是多肽的通过此项技术中熟知的任何方法，包括例如通过免疫分析确定的抗体所结合的部分。抗原性表位未必具有免疫原性。表位通常由分子的化学活性表面基团，如氨基酸或糖侧链组成，并且具有特定的三维结构特征以及特定的电荷特征。抗体表位可为线性表位或构象表位。线性表位是由蛋白质中的连续氨基酸序列形成的。构象表位是由在蛋白质序列中不连续但在蛋白质折叠成其三维结构时结合在一起的氨基酸形成的。当蛋白质的三维结构呈改变的构象时，如在另一种蛋白质或配体活化或结合之后，形成诱导性表位。在某些实施方案中，表位是多肽的三维表面特征。在其他实施方案中，表位是多肽的线性特征。一般来说，抗原具有若干或许多不同的表位，并且可与许多不同的抗体反应。
脂质组合物
在一个实施方案中，本申请提供一种式(I)的化合物：
或其药学上可接受的盐、前药或立体异构体，其中：
所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；
所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；
Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；
x是0、1或2；
所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；
所述L3和L4各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；
Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；
i是0、1或2；
所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；
所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；
其中，Re和Rf为任选地取代的C1-C12亚烷基；
G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；
Rg为任选地取代的C1-C12亚烷基；
所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环；
优选地，Z为任选地取代的C1-C12亚烷基，所述化合物是式(I-A)的结构：
其中，G1、G2、G3、G4、G5、G6、L1、L2、L3、L4、X和Y如式(I)中所定义，G8为任选地取代的C1-C12亚烷基。
或者优选地，任选地取代的-ReG7Rf-，所述化合物具有式(I-B)所示的结构：
其中，G1、G2、G3、G4、G5、G6、G7、L1、L2、L3、L4、Re、Rf、X和Y如式(I)中所定义；优选地，G1和G2是未被取代的C2-C4亚烷基，所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基；所述X和Y各自独立地任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
优选地，L1和L2是-C(＝O)O-，所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
优选地，G3和G4为键或未被取代的C2-C4亚烷基，所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、 -SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
优选地，L3和L4为键或-OC(＝O)O-，所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
优选地，L3和L4为键，所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
优选地，G5和G6为任选地取代的C4-C16直链烯基，所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代 的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述Z为任选地取代的 C1-C12亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C12亚烷基；G7为-NRg-、(3-7元饱和环亚烷烃)、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；Rg为任选地取代的C1-C12亚烷基。
一种具体的实施方式中，Z为C2-C4亚烷基，所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
一种具体的实施方式中，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立 地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；x是0、1或2；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、 -NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代 的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；i是0、1或2；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-； 所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷 基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独 立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自 独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基； 所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷 基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的- ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16 直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自 独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；、所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基； 所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷 基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的- ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为C2-C4亚烷基；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为-G1L1G3L3G5，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为任选地取代的C1-C3直链烷基，Y为-G1L1G3L3G5，Z为任选地取代 的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X为-G1L1G3L3G5，Y为任选地取代的C1-C3直链烷基，Z为任选地取代的-ReG7Rf-，Re和Rf为任选地取代的C2-C4亚烷基，G7为-(3-7元杂环亚烷烃)-；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
一种具体的实施方式中，X和Y各自独立地为C1-C3直链烷基，Z为C2-C4亚烷基，且X、Z连同其所连接的氮成环；所述G1和G2各自独立地为未被取代的C2-C4直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4为键或未被取代的C2-C4亚烷基；所述L3和L4各自独立地为键；、所述G5和G6各自独立地为任选地取代的C4-C16直链烯基。
进一步优选地，所述化合物具有式(I-A-1)所示的结构：
其中，m为1或3，n为0或1，G5和G6为任选地取代的C4-C16直链烯基，G8为式(I-A)所定义，G9和G10为任选地取代的C1-C5直链烷烃。
或者进一步优选地，所述化合物具有式(I-A-2)所示的结构：
其中，m为1或3，n为0或1，G5和G6为任选地取代的C4-C16直链烯基。
或者进一步优选地，所述化合物具有式(I-A-3)所示的结构：
其中，m为1或3，n为0或1，G5和G6为任选地取代的C4-C16直链烯基。
或者进一步优选地，所述化合物具有式(I-A-4)所示的结构：
其中，G1、G2、G3、G4、G5、G6、L1、L2、L3、L4和Y的定义如(I)所示的化合物中所定义；G8为任选地取代的C1-C12亚烷基。
或者进一步优选地，所述化合物具有式(I-A-5)所示的结构：
其中，m为1或3，n为0或1，Y、G5和G6的定义如(I)所示的化合物中所定义；G8为任选地取代的C1-C12亚烷基。
或者进一步优选地，所述化合物具有式(I-A-6)所示的结构：
其中，m为1或3，n为0或1，Y、G5和G6的定义如(I)所示的化合物中所定义。
或者进一步优选地，所述化合物具有式(I-B-1)所示的结构：
其中，m为1或3，n为0或1，G5和G6为任选地取代的C4-C16直链烯基。
或者进一步优选地，所述化合物具有式(I-B-2)所示的结构：
其中，m为1或3，n为0或1，G5和G6为任选地取代的C4-C16直链烯基。
或者进一步优选地，所述化合物具有式(I-B-3)所示的结构：
或者进一步优选地，所述化合物具有式(I-B-1)所示的结构：
其中，G1、G2、G3、G4、G5、G6、G7、L1、L2、L3、L4、Re和Rf如(I)所示的化合物中所定义。
其中，m为1或3，n为0或1，G5和G6为任选地取代的C4-C16直链烯基。
更优选地，G8为任选地取代的C2-C4亚烷基；
更优选地，G9或G10或两者具有以下结构之一：甲基、乙基、2-羟基乙基；
更优选地，G5或G6或两者具有以下结构之一：
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C4亚烷基；G7为-(3-7元杂环亚烷烃)-；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C4亚烷基；G7为-(3-7元杂环亚烷烃)-；所述X和Y各自独立地为任选地取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选地取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和 G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为羟基或胺基取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为C1-C4直链烷基，Y为羟基取代的C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为G1L1G3L3G5，Y为胺基取代的C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选取代的C2-C24直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C4亚烷基；G7为-(3-7元杂环亚烷烃)-；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C4亚烷基；G7为-(3-7元杂环亚烷烃)-；所述X和Y各自独立地为任选地取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选地取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和 Y各自独立地为任选取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为羟基或胺基取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为C1-C4直链烷基，Y为羟基取代的C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选地取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为G1L1G3L3G5，Y为胺基取代的C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为任选取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C4亚烷基；G7为-(3-7元杂环亚烷烃)-；所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基、任选地取代的-ReG7Rf-；其中，Re和Rf为任选地取代的C1-C4亚烷基；G7为-(3-7元杂环亚烷烃)-；所述X和Y各自独立地为任选地取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键或任选地取代的C2-C4直链亚烷基；所述L3和L4各自独立地为键或-OC(＝O)O-；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选地取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选取代的C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为任选取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直 链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为羟基或胺基取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为C1-C4直链烷基，Y为羟基取代的C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为G1L1G3L3G5，Y为胺基取代的C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为C1-C4直链烷基。
一种具体的实施方式中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为G1L1G3L3G5。
一种具体的实施方式，当由M0型向M1型极化时，式(I)化合物为其中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为羟基或胺基取代的C1-C4直链烷基或-G1L1G3L3G5，前提是X和Y不同时为C1-C4直链烷基或-G1L1G3L3G5。
一种具体的实施方式，当由M0型向M1型极化时，式(I)化合物为其中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为C1-C4直链烷基，Y为羟基取代的C1-C4直链烷基。
一种具体的实施方式，当由M2型向M0型极化时，式(I)化合物为其中，，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X为G1L1G3L3G5，Y为胺基取代的C1-C4直链烷基。
一种具体的实施方式，当由M2型向M0型极化时，式(I)化合物为其中，所述G1和G2各自独立地为任选地取代的C2直链亚烷基；所述L1和L2各自独立地为-C(＝O)O-；所述G3和G4各自独立地为键；所述L3和L4各自独立地为键；所述G5和G6各自独立地为C2-C4烷基取代的C12-C16直链烯基；所述Z为任选地取代的C2-C4亚烷基；所述X和Y各自独立地为G1L1G3L3G5。
本申请提供了下列表1中的化合物或其药物可用的盐、前药或立体异构体：
表1代表性化合物






本申请进一步提供一种组合物，包括治疗剂或预防剂；以及用于递送所述治疗剂或预防剂的载体，其中，所述载体包括阳离子脂质，所述阳离子脂质包括如上任一本申请所提供的阳离子脂质化合物、或其药物可用的盐中的一种或多种。
本申请的组合物中，治疗剂或预防剂可以是核酸分子、小分子化合物、多肽或蛋白质，也可以是其中两种或以上的混合。
一种具体的实施方式中，所述核酸分子选自单链DNA、双链DNA、短异构体、agomir、antagomir、反义分子、小干扰RNA(siRNA)、不对称干扰RNA(aiRNA)、microRNA(miRNA)、Dicersubstrate RNA(dsRNA)、小发夹RNA(shRNA)、转移RNA(tRNA)、信使RNA(mRNA)和本领域已知的其他形式的RNA分子，或锁核酸(LNA)、肽核酸(PNA)和吗啉环寡聚核苷酸等核酸模拟物。
一种具体的实施方式中，所述治疗剂或预防剂包含至少一种编码抗原或其片段或表位的mRNA，优选的，所述mRNA是单顺反子mRNA或多顺反子mRNA。
一种具体的实施方式中，所述抗原是病原性抗原。
一种具体的实施方式中，所述mRNA包含一种或多种功能性核苷酸类似物，优选的，所述功能性核苷酸类似物选自假尿嘧啶核苷、1-甲基-假尿嘧啶核苷或5-甲基胞嘧啶中的一种或多种。
一种具体的实施方式中，所述小分子化合物选自抗肿瘤药、抗感染药、局部麻醉药、抗抑郁药、抗惊厥药、抗生素/抗菌剂、抗真菌药、抗寄生虫药、激素、激素拮抗剂、免疫调节剂、神经递质拮抗剂、抗青光眼剂、麻醉剂或成像剂中的一种或多种。
如上所述本申请提供的组合物中，其中载体与治疗剂或预防剂的量本申请不做限制，一种具体的实施方式中，所述载体与所述治疗剂或预防剂的质量比为1.5：2～50：1，例如可以为0.75：1、1：1、2：1、3：1、4：1、5：1、6：1、7：1、8：1、9：1、10：1、11：1、12：1、13：1、14：1、15：1、16：1、17：1、18：1、19：1、20：1、25：1、30：1、35：1、40：1、41：1、42：1、43：1、44： 1、45：1、46：1、47：1、48：1、49：1。
一种具体的实施方式中，本申请的组合物为纳米颗粒制剂，所述纳米颗粒制剂的平均尺寸为10～500nm，例如可以为20nm、30nm、40nm、50nm、60nm、70nm、80nm、90nm、100nm、150nm、200nm、250nm、300nm、350nm、400nm、450nm。
一种具体的实施方式中，本申请的纳米颗粒制剂的pKa为4.5～8.5，例如可以为4.6、4.7、4.8、4.9、5、5.1、5.2、5.3、5.4、5.5、5.6、5.7、5.8、5.9、6、6.5、7、7.5、8、8.1、8.2、8.3、8.4。
如上所述本申请提供的组合物，其中，所述载体进一步包含一种或多种中性脂质，优选，所述中性脂质选自磷脂酰胆碱、磷脂酰乙醇胺、鞘磷脂、神经酰胺、甾醇及其衍生物中的一种或多种。
一种具体的实施方式中，其中所述阳离子脂质与所述中性脂质的摩尔比在约100：1至约5:1的范围内，例如可以为90：1、85：1、80：1、75：1、70：1、65：1、60：1、55：1、50：1、45：1、40：1、35：1、30：1、25：1、20：1、15：1、10：1。
一种具体的实施方式中，所述类固醇为选自胆固醇、非甾醇、谷固醇、麦角固醇、菜油甾醇、豆甾醇、芸苔甾醇、番茄碱、番茄碱、熊果酸、α-生育酚、皮质类固醇中的一种或多种。
一种具体的实施方式中，其中所述阳离子脂质与所述类固醇的摩尔比在约2:1至约4:1的范围内，例如可以为2.1：1、2.2：1、2.3：1、2.4：1、2.5：1、2.6：1、2.7：1、2.8：1、2.9：1、3：1、3.1：1、3.2：1、3.3：1、3.4：1、3.5：1、3.6：1、3.7：1、3.8：1、3.9：1。
如上所述本申请提供的组合物，其中，所述组合物载体进一步包含一种或多种能够与聚合物结合的脂质，优选，所述能够与聚合物结合的脂质为选自PEG修饰的磷脂酰乙醇胺、PEG修饰的磷脂酸、PEG修饰的神经酰胺、PEG修饰的二烷基胺、PEG修饰的二酰基甘油、PEG修饰的二烷基甘油中的一种或多种。
一种具体的实施方式中，其中所述阳离子脂质与所述能够与聚合物结合的脂质的摩尔比在约100:1至约20:1的范围内，例如可以为95:1、90：1、85：1、80：1、75：1、70：1、65：1、60：1、55：1、50：1、45：1、40：1、35：1、30：1、25：1。
一种具体的实施方式中，本申请的组合物中，所述载体还包括中性脂质、结构脂质以及聚合物共轭脂质，所述阳离子脂质、所述中性脂质、所述类固醇脂质、以及所述聚合物共轭脂质的摩尔比为(15～70)：(1～15)：(15～35)：(0～3)。
一种具体的实施方式中，本申请的组合物中，所述载体还包括中性脂质和结构脂质，所述阳离子脂质、所述中性脂质、所述类固醇脂质的摩尔比为(15～70)：(1～15)：(15～35)。
一种具体的实施方式中，所述的组合物还包括药物可用的赋形剂。
一种具体的实施方式中，所述的赋形剂包括药物可用的稀释剂。
本申请进一步提供了如上任一项本申请提供的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体在制备药物中的应用。
本申请进一步提供了如上任一项本申请提供的组合物在制备药物中的应用。
一种具体的实施方式中，所述药物为选自基因药物、核酸疫苗、小分子药物、多肽或蛋白质药物中的任一种。
本申请进一步提供了如上任一项本申请提供的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体或如上任一项本申请提供的组合物在靶向免疫细胞中的用途。
本申请进一步提供了如上任一项本申请提供的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体或如上任一项本申请提供的组合物在制备靶向免疫细胞的药物中的用途。
在上述用途中，一种具体的实施方式，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞。
本申请进一步提供了如上任一项本申请提供的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体或如上任一项本申请提供的组合物在促进细胞极化中的用途。
本申请进一步提供了如上任一项本申请提供的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体或如上任一项本申请提供的组合物在制备促进免疫细胞极化的药物中的用途。
在促进细胞极化中的用途或制备促进免疫细胞极化的药物中的用途中，一种具体的实施方式，所述细胞极化为由M0型向M1型极化。
在促进细胞极化中的用途或制备促进免疫细胞极化的药物中的用途中，一种具体的实施方式，所述细胞极化为由M2型向M0型极化。
在促进细胞极化中的用途或制备促进免疫细胞极化的药物中的用途中，一种具体的实施方式，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞。优选为巨噬细胞。
本申请进一步提供了一种体外筛选脂质纳米颗粒的方法，其包括：
在巨噬细胞细胞系中进行第一次筛选，获得可以转染巨噬细胞细胞系的脂质纳米颗粒；
在获得的脂质纳米粒颗粒中选择FLuc荧光信号强度高于10000RLUs的脂质纳米粒颗粒在骨髓来源的原代巨噬细胞中进行第二次筛选；
第二次筛选后获得目标脂质纳米颗粒。
一种具体的实施方式中，其中，所述巨噬细胞细胞系为Raw264.7细胞系。
一种具体的实施方式中，其中，所述FLuc荧光信号强度高于10000RLUs可以是高于20000RLUs、30000RLUs、40000RLUs、50000RLUs、60000RLUs、70000RLUs、80000RLUs、90000RLUs、100000RLUs、110000RLUs、120000RLUs、130000RLUs、140000RLUs、150000RLUs、160000RLUs、170000RLUs、180000RLUs、190000RLUs、200000RLUs及以上。
本申请进一步提供了一种筛选适用于体内免疫细胞mRNA递送的脂质纳米粒颗粒的方法，其包括：
将包裹携带报告基因的CAR-mRNA的脂质纳米粒颗粒经尾静脉注射入野生型小鼠，筛选获得在给定器官有表达且表达比例高于80％的第一脂质纳米粒颗粒；
任选的，将筛选获得第一脂质纳米粒颗粒包裹携带报告基因的CAR-mRNA，瘤内注射荷瘤小鼠，筛选获得只在肿瘤部位表达，其他器官不表达，且稳定表达24～48h的第二脂质纳米粒颗粒；所述其他器官是指没有肿瘤的器官；
将筛选获得第一或第二脂质纳米粒颗粒经尾静脉注射入Cre报告基因小鼠，筛选获得在免疫细胞具有Td tomato+细胞的目标脂质纳米粒颗粒。
一种具体的实施方式中，所述Td tomato+细胞的数目越多，筛选获得的脂质纳米粒颗粒具有更好的适用于体内免疫细胞mRNA递送的效果，但本申请对此不做限制，只有具有Td tomato+细胞即符合筛选方法的要求。
一种具体的实施方式中，其中，所述给定器官选自脾脏或骨髓。
一种具体的实施方式中，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞中的任意一种。
一种具体的实施方式中，如上所述目标脂质纳米颗粒为本申请提供的及的式(I)的化合物或其药学上可接受的盐、前药或立体异构体所制备得到。
具体实施方式
下面结合具体实施方式，进一步阐明本申请，但这些实施例仅用于说明本申请而不用于限制本申请的范围。实施例中采用的实施条件可以根据具体使用的不同要求做进一步调整，未注明的实施条件为本行业中的常规条件。本申请各个实施方式中所涉及到的技术特征只要彼此之间未构成冲突就可以相互组合。
本申请中具体实施例中，所使用的原料均可通过市售获得。
实施例一
实施例1.1化合物1的合成
合成路线
步骤1：中间体1-2的合成
向香叶醇(5g，16.86mmol，1eq)和三乙胺(2.33mL，16.86mmol，1eq)的二氯甲烷(100mL)中，缓慢滴加用二氯甲烷溶解的对硝基苯基氯甲酸酯(4.07g，20.03mmol，1.2eq)。反应混合物室温搅拌3h停止反应，加水萃取，合并有机层经MgSO4干燥，并真空除去溶剂，得到粗产物1-1。在装有粗产物1-1的250mL圆底瓶中加入丙烯酸羟乙酯(2.11g，20.03mmol，1.2eq)、碳酸钾(2.76g，20.03mmol，1.2eq)和N,N-二甲基甲酰胺溶剂(200mL),80℃搅拌3h，TLC显示化合物1-1完全消失。真空除去DMF后，用盐水洗涤，合并有机层经MgSO4干燥，并真空除去溶剂，得到粗产物，将粗产物经过柱层析法纯化(洗脱液为PE/EA＝10/1)，并将纯产物馏分蒸发，得到微黄色油状化合物1-2(10.06g，69％)。1H NMR(400MHz,CDCl3)δ6.44(dt,J＝17.4,1.2Hz,1H),6.14(ddd,J＝17.3,10.4,1.0Hz,1H),5.86(dt,J＝10.5,1.2Hz,1H),5.45–5.33(m,1H),5.07(dt,J＝6.8,3.4Hz,1H),4.68(d,J＝7.2Hz,2H),4.39(d,J＝1.0Hz,4H),2.13–2.04(m,4H),1.72(s,3H),1.68(s,3H),1.60(s,3H).
步骤2：化合物1的合成
在70℃将N,N-二甲基乙二胺(30μL，0.33mmol，1eq)和化合物1-2(300μL，1.01mmol，3eq)混合搅拌48h，混合物通过柱色谱法(硅胶柱，洗脱液为含0-10％甲醇(体积百分比)的二氯甲烷溶液)纯化，得到化合物1(370mg，54％)，为微黄色油状物。1H NMR(400MHz,CDCl3)δ5.38(t,J＝6.6Hz,2H),5.08(s,2H),4.67(d,J＝7.2Hz,4H),4.38–4.25(m,8H),2.79(t,J＝7.0Hz,4H),2.63(s,2H),2.49(t,J＝6.9Hz,6H),2.35(s,6H),2.12–2.02(m,8H),1.70(d,J＝15.9Hz,12H),1.58(d,J＝11.9Hz,6H).
实施例1.2化合物2的合成
以与实施例1.1中的方法制备化合物2。1H NMR(400MHz,CDCl3)δ5.43–5.27(m,2H),5.08(s,2H),4.67(d,J＝7.2Hz,2H),4.60(dd,J＝13.8,7.0Hz,2H),4.28(dt,J＝36.3,19.1Hz,6H),2.74(dd,J＝21.3,14.6Hz,5H),2.62(s,6H),2.44(ddd,J＝32.9,16.7,9.9Hz,6H),2.13–2.02(m,8H),1.88(s,2H),1.73–1.67(m,12H),1.60(s,6H),1.27(d,J＝12.3Hz,3H).
实施例1.3化合物3的合成
以与实施例1.1中的方法制备化合物3。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.1Hz,4H),5.06(d,J＝6.6Hz,4H),4.66(d,J＝7.2Hz,8H),4.33–4.28(m,16H),2.78(t,J＝7.0Hz,9H),2.49(dd,J＝22.3,15.4Hz,16H),2.23(s,2H),2.06(dd,J＝11.6,6.0Hz,16H),1.69(d,J＝16.1Hz,24H),1.59(s,12H).
实施例1.4化合物4的合成
以与实施例1.1中的方法制备化合物4。1H NMR(400MHz,CDCl3)δ5.31(t,J＝7.0Hz,4H),5.00(d,J＝6.5Hz,4H),4.60(d,J＝7.2Hz,8H),4.24(dd,J＝13.2,5.0Hz,18H),2.68(t,J＝6.6Hz,8H),2.39(t,J＝6.7Hz,17H),2.09–1.86(m,20H),1.63(d,J＝16.2Hz,24H),1.53(s,12H).
实施例1.5化合物5的合成
以与实施例1.1中的方法制备化合物5。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.0Hz,3H),5.07(d,J＝6.6Hz,3H),4.67(d,J＝7.2Hz,6H),4.31(dd,J＝13.5,5.6Hz,12H),2.75(t,J＝7.1Hz,6H),2.66(s,3H),2.56–2.33(m,19H),2.15–1.99(m,14H),1.73–1.67(m,18H),1.60(s,9H).
实施例1.6化合物6的合成
以与实施例1.1中的方法制备化合物6。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.2Hz,2H),5.08(t,J＝6.2Hz,2H),4.66(t,J＝8.5Hz,4H),4.41–4.24(m,8H),2.87–2.52(m,14H),2.43(t,J＝6.9Hz,7H),2.12–2.02(m,8H),1.73–1.67(m,12H),1.60(s,6H),1.08(dt,J＝36.4,6.0Hz,4H),0.93(d,J＝6.5Hz,3H).
实施例1.7化合物H77合成
以与实施例1.1中的方法制备化合物7。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.2Hz,4H),5.08(t,J＝6.3Hz,4H),4.67(d,J＝7.2Hz,8H),4.34–4.27(m,16H),2.75(t,J＝7.0Hz,8H),2.46(t,J＝7.0Hz,16H),2.31(s,6H),2.16–2.00(m,18H),1.70(d,J＝16.4Hz,28H),1.60(s,12H).
实施例1.8化合物8的合成
以与实施例1.1中的方法制备化合物8。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.2Hz,2H),5.07(d,J＝6.8Hz,2H),4.67(d,J＝7.2Hz,4H),4.31(ddd,J＝8.2,5.1,2.1Hz,8H),2.75(ddd,J＝48.6,13.4,6.5Hz,4H),2.49–2.41(m,8H),2.30(s,2H),2.07(dd,J＝11.8,6.5Hz,8H),1.95(s,2H),1.72–1.67(m,12H),1.60(s,6H),1.52(s,3H),1.27(d,J＝12.2Hz,3H).
实施例1.9化合物9的合成
以与实施例1.1中的方法制备化合物9。1H NMR(400MHz,CDCl3)δ5.38(t,J＝6.9Hz,2H),5.08(t,J＝6.6Hz,2H),4.65(d,J＝7.2Hz,4H),4.13(dt,J＝26.9,5.9Hz,8H),2.79(t,J＝7.1Hz,4H),2.62(d,J＝6.6Hz,2H),2.45(t,J＝7.1Hz,6H),2.34(s,6H),2.12–2.02(m,8H),1.80–1.72(m,8H),1.70(d,J＝15.4Hz,12H),1.60(s,6H).
实施例1.10化合物10的合成
以与实施例1.1中的方法制备化合物10。1H NMR(400MHz,CDCl3)δ5.37(dd,J＝7.8,6.6Hz,2H),5.08(t,J＝6.7Hz,2H),4.65(d,J＝7.2Hz,4H),4.12(dt,J＝27.8,6.0Hz,8H),2.75(t,J＝7.1Hz,4H),2.42(dq,J＝14.0,7.3Hz,8H),2.31(s,6H),2.14–2.03(m,8H),1.78–1.72(m,8H),1.72(s,6H),1.68(s,6H),1.67–1.62(m,2H),1.60(s,6H).
实施例1.11化合物11的合成
以与实施例1.1中的方法制备化合物11。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.2Hz,4H),5.08(dd,J＝6.7,5.6Hz,4H),4.65(d,J＝7.2Hz,8H),4.17–4.06(m,16H),2.78(t,J＝7.1Hz,8H),2.72–2.48(m,8H),2.44(t,J＝7.1Hz,8H),2.26(d,J＝9.3Hz,3H),2.12–2.02(m,16H),1.74(s,10H),1.72(d,J＝4.3Hz,18H),1.68(s,12H),1.60(s,12H).
实施例1.12化合物12的合成
以与实施例1.1中的方法制备化合物12。1H NMR(400MHz,CDCl3)δ5.37(dd,J＝7.2,6.1Hz,4H),5.08(t,J＝6.7Hz,4H),4.65(d,J＝7.2Hz,8H),4.12(dt,J＝28.4,5.9Hz,17H),2.74(d,J＝6.5Hz,9H),2.42(t,J＝7.0Hz,12H),2.16–2.00(m,18H),1.73(dd,J＝6.5,3.4Hz,30H),1.68(s,14H),1.60(s,15H).
实施例1.13化合物13的合成
以与实施例1.1中的方法制备化合物13。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.2Hz,3H),5.08(t,J＝6.5Hz,3H),4.65(d,J＝7.2Hz,6H),4.17–4.07(m,12H),2.75(t,J＝7.2Hz,6H),2.53–2.29(m,20H),2.12–2.02(m,12H),1.78–1.73(m,11H),1.72(s,12H),1.68(s,10H),1.60(s,8H),1.57–1.52(m,2H).
实施例1.14化合物14的合成
以与实施例1.1中的方法制备化合物14。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.2Hz,3H),5.09(s,6H),4.67(d,J＝7.2Hz,4H),4.31(dd,J＝13.6,5.1Hz,12H),2.74(t,J＝6.7Hz,6H),2.44(dd,J＝24.0,17.5Hz,20H),2.12–1.87(m,26H),1.77–1.63(m,22H),1.60(s,18H).
实施例1.15化合物15的合成
以与实施例1.1中的方法制备化合物15。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.1Hz,4H),5.08(t,J＝6.3Hz,4H),4.65(d,J＝7.2Hz,8H),4.12(dt,J＝28.2,5.6Hz,18H),2.75(t,J＝7.1Hz,8H),2.42(t,J＝7.2Hz,16H),2.13–1.99(m,18H),1.73(dd,J＝6.2,3.2Hz,30H),1.68(s,15H),1.60(s,15H).
实施例1.16化合物16的合成
以与实施例1.1中的方法制备化合物16。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.2Hz,2H),5.08(t,J＝6.6Hz,2H),4.65(d,J＝7.2Hz,4H),4.12(dt,J＝27.1,5.9Hz,8H),2.87–2.67(m,4H),2.49–2.34(m,9H),2.14–2.00(m,9H),1.92(dd,J＝19.8,12.4Hz,3H),1.79–1.69(m,16H),1.68(s,6H),1.60(s,6H),1.46(d,J＝17.4Hz,3H).
实施例1.17化合物17的合成
以与实施例1.1中的方法制备化合物17。1H NMR(400MHz,CDCl3)δ5.13–5.03(m,2H),4.31(dd,J＝11.0,5.0Hz,8H),4.24–4.15(m,4H),2.80(t,J＝7.1Hz,4H),2.64–2.58(m,2H),2.56–2.37(m,8H),2.31(s,6H),1.97(ddd,J＝22.2,14.8,7.3Hz,4H),1.74(dd,J＝12.7,7.0Hz,2H),1.68(s,6H),1.60(s,6H),1.53–1.45(m,2H),1.36–1.15(m,4H),0.92(d,J＝6.4Hz,6H).
实施例1.18化合物18的合成
以与实施例1.1中的方法制备化合物18。1H NMR(400MHz,CDCl3)δ5.08(t,J＝7.1Hz,2H),4.34–4.27(m,8H),4.20(ddd,J＝14.1,8.4,4.3Hz,4H),2.76(t,J＝7.0Hz,4H),2.47(t,J＝6.8Hz,6H),2.33(d,J＝7.3Hz,2H),2.29(s,6H),2.02–1.92(m,4H),1.73–1.67(m,8H),1.63–1.57(m,8H),1.50(dd,J＝13.3,7.2Hz,2H),1.39–1.12(m,6H),0.92(d,J＝6.5Hz,6H).
实施例1.19化合物19的合成
以与实施例1.1中的方法制备化合物19。1H NMR(400MHz,CDCl3)δ5.08(dd,J＝7.7,6.5Hz,4H),4.31(dd,J＝11.7,5.6Hz,18H),4.19(dd,J＝13.5,6.5Hz,8H),2.79(t,J＝7.1Hz,8H),2.55–2.40(m,16H),1.98(dt,J＝14.8,7.2Hz,8H),1.75–1.69(m,4H),1.68(s,12H),1.60–1.52(m,17H),1.51–1.43(m,4H),1.34(dt,J＝11.7,7.1Hz,4H),1.20(ddd,J＝13.7,8.0,5.4Hz,4H),0.92(d,J＝6.5Hz,12H).
实施例1.20化合物20的合成
以与实施例1.1中的方法制备化合物20。1H NMR(400MHz,CDCl3)δ5.08(td,J＝7.1,1.2Hz,4H),4.31(dd,J＝11.9,5.1Hz,16H),4.19(dd,J＝13.7,6.2Hz,8H),2.75(t,J＝6.9Hz,8H),2.46(d,J＝7.0Hz,12H),2.23(d,J＝42.7Hz,4H),1.98(dt,J＝21.3,7.3Hz,8H),1.74–1.64(m,20H),1.61–1.49(m,23H),1.37–1.10(m,8H),0.92(d,J＝6.5Hz,12H).
实施例1.21化合物21的合成
以与实施例1.1中的方法制备化合物21。1H NMR(400MHz,CDCl3)δ5.08(td,J＝7.1,1.2Hz,3H),4.34–4.29(m,12H),4.21–4.16(m,6H),2.74(d,J＝7.0Hz,6H),2.49–2.25(m,24H),1.98(dt,J＝21.2,7.3Hz,6H),1.75–1.67(m,14H),1.60–1.54(m,13H),1.41–1.11(m,6H),0.92(d,J＝6.1Hz,9H).
实施例1.22化合物22的合成
以与实施例1.1中的方法制备化合物22。1H NMR(400MHz,CDCl3)δ5.08(t,J＝7.1Hz,2H),4.34–4.14(m,12H),2.77(ddd,J＝20.0,13.3,7.0Hz,3H),2.71–2.53(m,9H),2.53–2.37(m,6H),2.04–1.92(m,4H),1.77–1.70(m,2H),1.68(s,6H),1.60(s,6H),1.58–1.47(m,4H),1.41–1.33(m,3H),1.26–1.14(m,4H),1.06(dt,J＝28.0,7.1Hz,4H),0.92(dd,J＝6.5,2.6Hz,9H).
实施例1.23化合物23的合成
以与实施例1.1中的方法制备化合物23。1H NMR(400MHz,CDCl3)δ5.08(t,J＝7.0Hz,4H),4.31(dd,J＝12.8,5.8Hz,16H),4.22–4.15(m,8H),2.75(t,J＝6.9Hz,8H),2.54–2.21(m,21H),1.98(td,J＝14.4,7.3Hz,8H),1.79–1.69(m,5H),1.68(s,12H),1.60(s,14H),1.57–1.44(m,8H),1.28(dddd,J＝30.2,23.0,11.5,6.7Hz,12H),0.92(d,J＝6.5Hz,12H).
实施例1.24化合物24的合成
以与实施例1.1中的方法制备化合物24。1H NMR(400MHz,CDCl3)δ5.08(t,J＝7.1Hz,2H),4.35–4.30(m,6H),4.22–4.14(m,4H),2.83–2.67(m,4H),2.54–2.30(m,10H),2.20(s,2H),2.06–1.80(m,8H),1.73(td,J＝7.6,2.2Hz,3H),1.68(s,6H),1.60(s,7H),1.49(tdd,J＝32.3,19.6,12.6Hz,6H),1.35–1.14(m,4H),0.92(d,J＝6.5Hz,6H).
实施例1.25化合物25的合成
以与实施例1.1中的方法制备化合物25。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.2Hz,2H),5.09(s,4H),4.67(d,J＝7.2Hz,4H),4.31(dd,J＝12.9,5.7Hz,8H),2.79(t,J＝7.0Hz,4H),2.64(s,2H),2.49(t,J＝7.0Hz,6H),2.35(s,6H),2.08(dt,J＝16.2,6.9Hz,12H),1.99–1.94(m,4H),1.72(s,6H),1.68(s,6H),1.60(s,12H).
实施例1.26化合物26的合成
以与实施例1.1中的方法制备化合物26。1H NMR(400MHz,CDCl3)δ5.42–5.28(m,2H),5.08(s,4H),4.74–4.51(m,4H),4.30(dd,J＝15.2,5.7Hz,6H),2.71(d,J＝6.5Hz,4H),2.65–2.37(m,12H),2.31(s,4H),2.12–2.01(m,12H),1.99–1.90(m,4H),1.73–1.65(m,12H),1.59(s,12H),1.28(m,2H).
实施例1.27化合物27的合成
以与实施例1.1中的方法制备化合物27。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.2Hz,4H),5.08(s,8H),4.66(d,J＝7.2Hz,8H),4.30(dd,J＝13.3,5.7Hz,16H),2.78(t,J＝7.1Hz,8H),2.62–2.33(m,16H),2.22(s,3H),2.07(dt,J＝22.4,7.8Hz,24H),1.99–1.90(m,8H),1.72(s,12H),1.67(s,12H),1.59(s,24H).
实施例1.28化合物28的合成
以与实施例1.1中的方法制备化合物28。1H NMR(400MHz,CDCl3)δ5.38(t,J＝7.0Hz,4H),5.09(s,8H),4.67(d,J＝7.2Hz,8H),4.31(dd,J＝13.8,5.6Hz,16H),2.76(s,8H),2.46(t,J＝7.0Hz,11H),2.27(s,3H),2.19–1.87(m,37H),1.78–1.66(m,24H),1.65–1.50(m,28H).
实施例1.29化合物29的合成
以与实施例1.1中的方法制备化合物29。
实施例1.30化合物30的合成
以与实施例1.1中的方法制备化合物30。1H NMR(400MHz,CDCl3)δ5.38(s,2H),5.09(s,4H),4.66(d,J＝7.0Hz,4H),4.30(d,J＝11.8Hz,8H),2.72(dd,J＝41.3,32.6Hz,12H),2.43(d,J＝6.6Hz,4H),2.19–1.97(m,18H),1.70(d,J＝17.8Hz,12H),1.59(s,12H),1.43–0.89(m,10H).
实施例1.31化合物31的合成
以与实施例1.1中的方法制备化合物31。1H NMR(400MHz,CDCl3)δ5.38(t,J＝6.8Hz,4H),5.09(s,8H),4.67(d,J＝7.2Hz,8H),4.34–4.26(m,16H),2.75(t,J＝7.0Hz,8H),2.46(t,J＝7.0Hz,16H),2.31(s,4H),2.15–2.01(m,26H),1.99–1.90(m,8H),1.70(d,J＝18.5Hz,27H),1.58(d,J＝11.1Hz,27H).
实施例1.32化合物32的合成
以与实施例1.1中的方法制备化合物32。1H NMR(400MHz,CDCl3)δ5.38(dd,J＝7.2,6.1Hz,2H),5.10(dd,J＝7.2,2.5Hz,4H),4.67(d,J＝7.2Hz,4H),4.36–4.27(m,8H),2.89–2.60(m,4H),2.49–2.40(m,8H),2.32–1.79(m,24H),1.73–1.67(m,12H),1.61–1.47(m,14H).
实施例1.33化合物33的合成
合成路线如下：
33.1中间体33-1的制备
原料法尼醇(10g，45.25mmol，1eq)溶解在50mL二氯甲烷中，滴加丙烯酰氯(54.30mmol，1.2eq)和三乙胺(67.88mmol，1.5eq)，反应过夜，混合物通过柱层析(PE/EA＝10:1)纯化，得到中间体33-1。1H NMR(400MHz,CDCl3)δ6.46–6.34(m,1H),6.12(dd,J＝17.3,10.4Hz,1H),5.86–5.76(m,1H),5.40(t,J＝7.0Hz,1H),5.17–5.03(m,2H),4.66(d,J＝7.3Hz,2H),2.16–2.03(m,6H),2.00–1.95(m,2H),1.78(s,3H),1.68(s,3H),1.60(s,6H).
33.2化合物33的制备
在70℃将N,N-二甲基乙二胺(32μL，0.36mmol，1eq)和化合物33-1(300μL，1.09mmol，3eq)混合搅拌48h，混合物通过柱色谱法(硅胶柱，洗脱液为含0-10％甲醇(体积百分比)的二氯甲烷溶液)纯化，得到化合物33(380mg，60％)，为微黄色油状物。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.2Hz,2H),5.14–5.04(m,4H),4.56(d,J＝7.2Hz,4H),2.79(t,J＝7.2Hz,4H),2.60(t,J＝7.1Hz,2H),2.45(t,J＝7.2Hz,6H),2.30(s,6H),2.13–2.04(m,12H),1.99–1.95(m,4H),1.76(s,6H),1.68(s,6H),1.60(s,12H).
实施例1.34化合物34的合成
以与实施例1.33中的方法制备化合物34。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.2Hz,2H),5.15–5.04(m,4H),4.56(d,J＝7.2Hz,4H),2.75(t,J＝7.2Hz,4H),2.48–2.35(m,8H),2.31(s,6H),2.17–2.04(m,12H),2.00–1.95(m,4H),1.76(s,6H),1.70–1.64(m,8H),1.60(s,12H).
实施例1.35化合物35的合成
以与实施例1.33中的方法制备化合物35。1H NMR(400MHz,CDCl3)δ5.33(t,J＝6.9Hz,4H),5.09(q,J＝6.6Hz,8H),4.56(d,J＝7.2Hz,8H),2.78(t,J＝7.2Hz,8H),2.44(t,J＝7.2Hz,15H),2.28–1.91(m,36H),1.76(s,12H),1.68(s,12H),1.58(d,J＝12.7Hz,24H).
实施例1.36化合物36的合成
以与实施例1.33中的方法制备化合物36。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.1Hz,4H),5.16–5.04(m,8H),4.56(d,J＝7.2Hz,8H),2.75(t,J＝7.2Hz,8H),2.42(t,J＝7.2Hz,12H),2.33–1.93(m,39H),1.76(s,12H),1.69(d,J＝9.1Hz,12H),1.58(d,J＝12.6Hz,28H).
实施例1.37化合物37的合成
以与实施例1.33中的方法制备化合物37。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.2Hz,3H),5.15–5.03(m,6H),4.56(d,J＝7.2Hz,6H),2.75(t,J＝7.4Hz,6H),2.45–2.32(m,14H),2.28(s,6H),2.08(dt,J＝15.6,5.8Hz,18H),2.01–1.95(m,6H),1.76(s,9H),1.70–1.64(m,11H),1.63–1.52(m,20H).
实施例1.38化合物38的合成
以与实施例1.33中的方法制备化合物38。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.1Hz,2H),5.15–5.04(m,4H),4.56(d,J＝7.2Hz,4H),2.84–2.50(m,10H),2.50–2.15(m,6H),2.13–1.92(m,17H),1.76(s,6H),1.69(d,J＝9.3Hz,7H),1.58(d,J＝12.8Hz,14H),1.43(d,J＝7.6Hz,2H),1.13(dd,J＝40.4,33.4Hz,4H),0.92(d,J＝6.5Hz,2H).
实施例1.39化合物39的合成
以与实施例1.33中的方法制备化合物39。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.2Hz,4H),5.16–5.03(m,8H),4.56(d,J＝7.3Hz,8H),2.75(t,J＝7.2Hz,8H),2.40(dd,J＝30.4,23.2Hz,20H),2.14–1.91(m,34H),1.77(s,12H),1.69(d,J＝9.1Hz,14H),1.64–1.54(m,28H).
实施例1.40化合物40的合成
以与实施例1.33中的方法制备化合物40。1H NMR(400MHz,CDCl3)δ5.34(t,J＝7.0Hz,2H),5.15–5.04(m,4H),4.56(d,J＝7.3Hz,4H),2.76(ddd,J＝20.3,13.2,6.3Hz,4H),2.44(d,J＝7.4Hz,8H),2.26(d,J＝8.9Hz,3H),2.15–1.86(m,20H),1.77(s,6H),1.69(d,J＝9.2Hz,7H),1.60(s,12H),1.48(dd,J＝54.9,23.8Hz,2H).
实施例1.41化合物41的合成
以与实施例1.33中的方法制备化合物41。1H NMR(400MHz,CDCl3)δ5.33(t,J＝7.1Hz,2H),4.59(d,J＝7.1Hz,4H),2.80(t,J＝7.2Hz,4H),2.61(t,J＝7.0Hz,2H),2.46(t,J＝7.2Hz,6H),2.31(s,6H),2.00(t,J＝6.5Hz,4H),1.69(s,6H),1.52(dd,J＝13.3,6.6Hz,2H),1.42–1.32(m,8H),1.31–1.03(m,28H),0.93–0.77(m,24H).
实施例1.42化合物42的合成
以与实施例1.33中的方法制备化合物42。1H NMR(400MHz,CDCl3)δ5.32(d,J＝7.1Hz,2H),4.59(d,J＝7.1Hz,4H),2.76(t,J＝7.0Hz,4H),2.48–2.33(m,8H),2.30(s,6H),2.00(s,4H),1.67(d,J＝14.0Hz,8H),1.52(dd,J＝13.2,6.6Hz,2H),1.22(ddd,J＝34.9,33.1,22.4Hz,36H),0.86(t,J＝6.4Hz,24H).
实施例1.43化合物43的合成
以与实施例1.33中的方法制备化合物43。1H NMR(400MHz,CDCl3)δ5.32(t,J＝7.2Hz,4H),4.60(dd,J＝11.5,7.1Hz,8H),2.79(t,J＝7.1Hz,8H),2.48(dd,J＝34.0,27.0Hz,16H),2.28(s,3H),1.99(d,J＝6.5Hz,8H),1.69(s,12H),1.52(dt,J＝13.2,6.6Hz,4H),1.41–1.03(m,72H),0.97–0.79(m,48H).
实施例1.44化合物44的合成
以与实施例1.33中的方法制备化合物44。1H NMR(400MHz,CDCl3)δ5.33(t,J＝7.1Hz,4H),4.58(d,J＝7.1Hz,8H),2.75(d,J＝6.8Hz,8H),2.43(t,J＝7.0Hz,12H),1.99(d,J＝6.1Hz,10H),1.69(s,14H),1.53(dt,J＝13.2,6.6Hz,6H),1.43–0.96(m,77H),0.92–0.81(m,48H).
实施例1.45化合物45的合成
以与实施例1.33中的方法制备化合物45。1H NMR(400MHz,CDCl3)δ5.32(t,J＝7.0Hz,3H),4.58(d,J＝7.1Hz,6H),2.76(t,J＝7.3Hz,6H),2.40(dd,J＝16.7,7.5Hz,12H),2.30(s,6H),2.00(t,J＝6.3Hz,6H),1.69(s,9H),1.59–0.99(m,63H),0.99–0.75(m,36H),
实施例1.46化合物46的合成
以与实施例1.33中的方法制备化合物46。1H NMR(400MHz,CDCl3)δ5.32(t,J＝7.0Hz,2H),4.57(d,J＝7.1Hz,4H),4.21–4.15(m,6H),3.62(t,J＝5.2Hz,2H),2.84–2.78(m,2H),2.72–2.58(m,8H),2.44–2.39(m,6H),2.21(td,J＝5.2,2.5Hz,2H),2.00–1.94(m,6H),1.74(dd,J＝7.6,4.5Hz,6H),1.68(s,6H),1.54–1.49(m,2H),1.41–1.35(m,6H),1.24(dd,J＝8.3,4.5Hz,8H),1.15–1.00(m,16H),0.87–0.80(m,24H).
实施例1.47化合物47的合成
以与实施例1.33中的方法制备化合物47。1H NMR(400MHz,CDCl3)δ5.32(t,J＝6.7Hz,4H),4.58(d,J＝7.1Hz,8H),2.75(t,J＝7.2Hz,8H),2.43(t,J＝7.1Hz,20H),2.00(t,J＝6.2Hz,8H),1.69(s,12H),1.63–0.98(m,84H),0.92–0.79(m,48H).
实施例1.48化合物48的合成
以与实施例1.33中的方法制备化合物48。1H NMR(400MHz,CDCl3)δ5.32(t,J＝7.0Hz,2H),4.58(d,J＝7.1Hz,4H),2.82(dd,J＝13.9,6.7Hz,2H),2.75–2.62(m,2H),2.49–2.29(m,10H),2.00(t,J＝6.5Hz,8H),1.69(s,6H),1.56–0.99(m,42H),0.93–0.76(m,24H).
实施例1.49化合物49的合成
以与实施例1.1中的方法制备化合物49。1H NMR(400MHz,CDCl3)δ5.37(s,2H),4.67(d,J＝6.8Hz,4H),4.31(d,J＝10.0Hz,8H),2.78(d,J＝6.5Hz,4H),2.72(s,2H),2.49(d,J＝6.0Hz,8H),1.95(d,J＝45.4Hz,6H),1.71(s,6H),1.52(dd,J＝12.4,5.9Hz,2H),1.37(s,10H),1.27(d,J＝11.5Hz,16H),1.16–1.03(m,12H),0.86(t,J＝7.1Hz,24H).
实施例1.50化合物50的合成
以与实施例1.1中的方法制备化合物H2T750。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.0Hz,2H),4.67(d,J＝7.2Hz,4H),4.31(qd,J＝6.3,2.6Hz,8H),2.74(t,J＝6.8Hz,4H),2.49–2.35(m,12H),2.00(t,J＝6.6Hz,6H),1.71(s,6H),1.53(dd,J＝13.3,6.7Hz,2H),1.35(dd,J＝14.5,6.1Hz,8H),1.31–1.19(m,16H),1.09(dddd,J＝14.8,12.4,10.5,7.1Hz,14H),0.85(dd,J＝8.7,6.7Hz,24H).
实施例1.51化合物51的合成
以与实施例1.1中的方法制备化合物51。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.2Hz,4H),4.67(d,J＝7.2Hz,8H),4.31(dd,J＝13.2,5.7Hz,16H),2.79(t,J＝6.9Hz,8H),2.48(s,17H),2.00(t,J＝6.2Hz,8H),1.71(s,12H),1.52(dt,J＝13.2,6.6Hz,4H),1.46–1.32(m,18H),1.32–1.18(m,32H),1.09(dddd,J＝14.6,12.1,10.3,7.1Hz,26H),0.90–0.81(m,48H).
实施例1.52化合物52的合成
以与实施例1.1中的方法制备化合物52。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.2Hz,4H),4.67(d,J＝7.2Hz,8H),4.31(dd,J＝13.9,5.6Hz,16H),2.74(s,8H),2.46(t,J＝6.7Hz,12H),2.00(d,J＝6.4Hz,10H),1.71(s,12H),1.65(s,6H),1.52(dd,J＝13.2,6.7Hz,4H),1.38(dd,J＝18.1,13.7Hz,18H),1.32–1.20(m,32H),1.14(dd,J＝11.4,4.5Hz,9H),1.11–1.01(m,16H),0.86(dd,J＝8.3,6.8Hz,48H).
实施例1.53化合物53的合成
以与实施例1.1中的方法制备化合物53。1H NMR(400MHz,CDCl3)δ5.36(d,J＝7.4Hz,3H),4.67(d,J＝7.2Hz,3H),4.29(dd,J＝15.6,6.4Hz,9H),2.74(d,J＝3.4Hz,6H),2.60(s,6H),2.52–2.35(m,12H),2.00(d,J＝6.0Hz,6H),1.70(d,J＝9.2Hz,10H),1.51(dt,J＝19.8,6.6Hz,6H),1.37(ddd,J＝15.7,11.6,4.4Hz,16H),1.30–1.20(m,26H),1.18–1.11(m,8H),1.07(ddd,J＝14.9,11.5,5.9Hz,12H),0.86(t,J＝7.6Hz,36H).
实施例1.54化合物54的合成
以与实施例1.1中的方法制备化合物54。1H NMR(400MHz,CDCl3)δ5.36(s,2H),4.81(d,J＝7.4Hz,2H),4.66(t,J＝6.1Hz,4H),4.35–4.24(m,6H),2.77(dd,J＝13.7,7.4Hz,3H),2.72–2.51(m,3H),2.43(t,J＝6.7Hz,3H),2.14–1.96(m,10H),1.77(s,3H),1.70(d,J＝7.4Hz,12H),1.64–1.57(m,6H),1.57–1.46(m,4H),1.45–1.32(m,8H),1.31–1.17(m,18H),1.13(dd,J＝11.6,4.5Hz,4H),1.09–1.00(m,6H),0.92(d,J＝6.4Hz,2H),0.85(dd,J＝8.5,6.6Hz,18H).
实施例1.55化合物55的合成
以与实施例1.1中的方法制备化合物55。1H NMR(400MHz,CDCl3)δ5.37(t,J＝7.1Hz,4H),4.67(d,J＝7.2Hz,8H),4.31(dd,J＝13.5,5.1Hz,16H),2.75(t,J＝6.9Hz,8H),2.59–2.21(m,22H),2.00(t,J＝6.5Hz,8H),1.71(s,16H),1.63–1.48(m,8H),1.22(dddd,J＝38.6,30.2,19.0,12.2Hz,80H),0.90–0.82(m,48H).
实施例1.56化合物56的合成
以与实施例1.1中的方法制备化合物56。1H NMR(400MHz,CDCl3)δ5.36(t,J＝6.8Hz,2H),4.67(d,J＝7.2Hz,3H),4.34–4.27(m,6H),2.83(dd,J＝13.6,6.9Hz,2H),2.63(dd,J＝13.8,7.4Hz,6H),2.52–2.41(m,6H),2.22–1.78(m,9H),1.70(d,J＝8.4Hz,8H),1.60–0.97(m,42H),0.85(dd,J＝8.5,6.7Hz,24H).
实施例1.57
制备纳米颗粒组合物
将实施例1.1-56制备的56个阳离子脂质化合物分别与胆固醇(艾伟拓(上海)医药科技有限公司)、DSPC醇(艾伟拓(上海)医药科技有限公司)和DMG-PEG2000(艾伟拓(上海)医药科技有限公司)以66.67:25.67:6.67:1.00的摩尔比溶解在无水乙醇中。以约10:1阳离子脂质与萤火虫荧光素酶(Fluc)mRNA的重量比制备脂质纳米颗粒(LNP)。简而言之，将mRNA在25mM醋酸钠溶液(pH 5.2)中稀释，使用注射器泵将脂质的乙醇溶液与mRNA水溶液以约1:3(体积/体积)的比例混合，总流速为12mL/min。通过透析除去乙醇将LNP置换到dd H2O中。最后，将脂质纳米颗粒通过0.2μm孔的无菌过滤器过滤，得到包封萤火虫荧光素酶mRNA的LNP制剂(LNP-mFluc)。
实施例1.58
利用脂质纳米颗粒组合物的荧光素酶mRNA体内评价
将实施例1.57中所制备的脂质纳米颗粒组合物(LNP-mFluc)分别进行荧光素酶mRNA体内评价。来自上海合信成生物的FLuc mRNA将表达荧光素酶蛋白，其最初从萤火虫中分离出来。Fluc通常用于哺乳动物细胞培养物中以测量基因表达和细胞活力。其在底物萤光素存在下发射出生物性光。根据实验动物管理委员会(ACC)和加拿大动物管理委员会(CCAC)制定的指南，5-6周龄的雌性Balb/c小鼠(上海斯莱克实验动物有限责任公司)上进行研究。通过尾静脉注射含5μg荧光素酶mRNA、50μg阳离子脂质纳米颗粒，给药后6h，将100μL 30mg/mL的D-荧光素钾盐(阿达玛斯试剂有限公司)腹腔注射到小鼠体内，10分钟后通过活体成像系统(PerkinElmer)对小鼠进行成像。其中，在肝脏中具有较强的荧光强度的化合物及其具体的荧光值如表2所示。化合物9、化合物32、化合物21、化合物8、化合物10、化合物33、化合物16、化合物30、化合物15、化合物2、化合物51、化合物56、化合物26、化合物25、化合物29、化合物5、化合物42、化合物53、化合物52、化合物13、化合物50在脾脏中具有较强的荧光信号，荧光强度基本在约1.17E+07以上，尤其是化合物50的荧光强度最高可达1.03E+08，在肺部具有较强信号的化合物17的荧光信号强度大约为6.95E+05。
表2肝脏中的荧光强度
实施例二
实施例2.1：体外筛选转染巨噬细胞LNP的方式(方法建立)
为了获得体外转染巨噬细胞的LNP，首先建立了体外筛选方法(图1)，具体步骤如下：第一步：将LNP库的LNP包裹luc-mRNA转染RAW264.7巨噬细胞细胞系进行初步筛选，通过酶标仪裂解细胞检测，以Luc荧光强度代表转染效率；第二步：选择细胞系中转染效率较高的LNP，将LNP包裹EGFP-mRNA转染小鼠骨髓来源的原代巨噬细胞(BMDM)中，进行进一步精细筛选，通过流式检测EGFP阳性细胞比例代表转染效率，最终获得目标体外转染原代巨噬细胞的LNP。
实施例2.2：LNP的制备方法
1、准备2.5μl、20μl、200μl、1000μl移液枪，10、200、1000μl无核酶无菌枪头，1.5ml离心管，15ml离心管，DEPC水，醋酸钠缓冲液(pH＝5.2)，75％酒精，无水乙醇，1.5ml离心管架，15/50ml离心管架(上述提及的液体、管等都是无核酶无菌)。
2、提前用无水乙醇分别配制胆固醇(艾伟拓(上海)医药科技有限公司)、DSPC醇(艾伟拓(上海)医药科技有限公司)、阳离子脂质、DMG-PEG2000(艾伟拓(上海)医药科技有限公司)的工作液，工作液浓度均为10mg/ml，封口保存在冰箱，防止乙醇挥发影响浓度。
3、按照阳离子脂质(1-42号，44-56号)、胆固醇、DSPC、DMG-PEG 2000其质量比为50：19.25:5:0.75；阳离子脂质(43号)、胆固醇、DSPC、DMG-PEG 2000其质量比为50： 35.77:9.29:1.39，取阳离子脂质、胆固醇、DSPC、DMG-PEG混合在一个1.5ml离心管里，加入一定体积无水乙醇，配制终浓度5mg/ml mix，涡旋1min混匀，超声1min，继续涡旋1min；另外取3倍体积25mM醋酸钠溶液(pH 5.2)，将mix匀速滴入涡旋状态下的醋酸钠缓冲液中，得到LNP。
实施例2.3：LNP-mRNA复合物1的制备
将实施例2.2制备的LNP置于透析袋(3.5K，Thermo Scientific)、超纯水室温透析3h以上；透析后的LNP浓度在0.8-1ug/ul之间，将LNP：RNA(w/w)＝10:1混合孵育15min，通过15ml 50KDa超滤离心管5000g浓缩，进行瘤内注射的复合物1，体积在30-50ul/mouse。
实施例2.4：LNP-mRNA复合物2的制备
将实施例2.2制备的LNP置于透析袋(3.5K，Thermo Scientific)、超纯水室温透析3h以上；透析后的LNP浓度在0.8-1ug/ul之间，将LNP：RNA(w/w)＝10:1混合孵育15min，获得尾静脉注射所用复合物2。
实施例2.5：LNP-mRNA复合物3的制备
将实施例2.2制备的LNP以LNP：RNA(w/w)＝10:1混合孵育15min，获得细胞转染所用复合物3。
实施例2.6：LNP-mRNA复合物递送Luc-mRNA至RAW264.7细胞
Raw264.7细胞接种培养于添加10％ FBS的DMEM高糖培养液的96孔板中,每孔铺2x104个细胞，其中含penicillin(100U/ml)和streptomycin(100μg/ml)。将实施例2.5制备的LNP-luc-RNA复合物3通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入10ul(即0.2ug RNA)，并培养20小时，通过萤火虫荧光素酶报告基因检测试剂盒(yeasen，11404ES60)裂解细胞，酶标仪进行细胞的荧光分析检测，得到LNP-RNA复合物的转染效率，结果如图2(从左到右依次为1-56号LNP)所示，1-56号LNP中大部分LNP均能转染RAW264.7细胞。例如，化合物43号、38号、37号、28号、27号、50号、53号、23号、48号、34号、29号、10号、19号、52号、40号、7号、42号、45号、41号、25号、13号、21号、56号、3号、15号、4号、16号、20号均具有很好的转染效果。
实施例2.7：LNP-mRNA复合物递送EGFP-mRNA至BMDM细胞
1、准备镊子、剪刀、2ml注射器、1ml注射器、70um细胞过滤网、6cm dish、预冷的PBS、红细胞裂解液、BMM培养基：10ng/ml M-CSF的DMEM完全培养基；75％乙醇；6孔板，在第一孔中加入75％的乙醇(为骨骼消毒)；向第二孔和第三孔加入约1mL培养基(用于冲洗骨头)，向板的第四孔加入3mL培养基(用于冲洗骨头)
2、脱颈处死C57小鼠，用75％乙醇浸泡2min，消毒杀菌；
2、沿腹中线剪开皮肤，暴露视野
3、再沿股骨向下剪开皮肤，去除毛发，分离股骨和胫骨，去掉脚部，用纸巾轻轻摩擦组织，效果最好，可以去掉去除骨头上多余的组织(即肌肉和脂肪)
4、将分离好的股骨和胫骨转入六孔板第一个孔，骨头浸泡在75％(孔/体积)的乙醇中1min。(破掉的骨头不要放在乙醇中)
5、将它们放入第二个装满1mL BMM培养基的孔中。
6、将它们移到第三个充满1mLBMM培养基的孔中。
7、用1ml注射器针头插在2ml注射器上，收集2mL新鲜的BMM培养基。
8、将胫骨从培养皿中取出，并以一定的角度在踝关节处切断。
9、收集骨髓a、胫骨在6cm dish上方保持胫骨的窄端指向下方。b、将针头插入骨髓的顶端并喷射培养基。c、收集6cm dish中2mL BMM培养基，然后再次插入。继续冲洗几次，当骨头为白色时，丢弃。
10、向6cm dish中补充至12ml培养基，轻轻吹匀。
11、将细胞悬液以每孔2ml铺在6孔板中，记为Day0。
12、Day7获得成熟的BMDM。
13、吸走六孔板BMM培养基上清，用PBS洗两遍，换成DMEM完全培养基。
14、选择27、28、37、38、43、50号LNP按照实施例2.5的方法制备LNP-EGFP-RNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入100ul(即2ug RNA)，并培养20小时，通过流式细胞仪(FACS)，检测F480+CD11b+EGFP+细胞百分比，即为LNP-RNA复合物的转染效率，结果如图3-1和图3-2所示。转染效率最高的LNP为43号。
实施例2.8：LNP-mRNA复合物递送CAR-CD19/HER2-mRNA至BMDM细胞
1、按照实施例2.7的方法(步骤1-13)获得成熟的BMDM细胞。
2、将选择43号LNP按照实施例2.5的方法制备LNP-CAR-CD19/HER2-RNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入100ul(即2ug RNA)，并培养20小时，通过流式细胞仪(FACS)，检测F480+CD11b+CAR-HER2+细胞百分比，即为LNP-mRNA复合物的转染效率，由flowjo分析软件生成，结果如图4所示。43号LNP在BMDM细胞中的转染效率在14％左右，直接证明了CAR mRNA的成功表达以及CAR-BMDM细胞的成功构建。
实施例2.9：LNP将M0-Raw264.7细胞极化成为M1型
Raw264.7细胞接种培养于添加10％ FBS的DMEM高糖培养液(HyClone,SH30022.01B)的6孔板中,每孔铺1x106个细胞，其中含penicillin(100U/ml)和streptomycin(100μg/ml)。将实施例2.6中转染效率较高的43号LNP(43号阳离子脂质、胆固醇、DSPC、DMG-PEG 2000比为50：35.77:9.29:1.39)和转染效率较低的LNP(称为43-1，43号阳离子脂质、胆固醇、DSPC、DMG-PEG 2000比为50：38.5:10:1.5)按照实施例2.5的方法制备LNP-EGFP-RNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul和0.03ug/ul，每孔加入100ul(即2ug RNA，20ug LNP和3ug RNA，30ug LNP)，并添加不包裹RNA的LNP作为对照，并培养20小时；弃上清，PBS洗两遍，细胞刮刀刮下，通过流式细胞仪(FACS)，检测F480+CD11b+细胞iNOS-APC的MFI，结果如图5-1(EGFP-Count流式直方图)和图5-2(iNOS-Count流式直方图，由flowjo分析软件生成)所示，LNP不仅可以递送mRNA，还可以促进巨噬细胞由M0向M1极化。由空LNP也可以导致极化现象可知，M1的极化主要是由于LNP导致的，而不是RNA导致的。由相同质量的43号LNP可以导致极化现象，而转染效率较低的43-1(图5-1)号LNP没有导致极化现象可知，发生M1的极化需要高转染效率的LNP。而43号LNP也只有达到一定剂量才能导致极化现象发生，说明发生M1的极化需要达到一定剂量的LNP。
实施例2.10：LNP将M0-BMDM细胞极化成为M1型
1、按照实施例2.7的方法(步骤1-13)获得成熟的BMDM细胞。
2、将选择27、28、37、38、43、50号LNP按照实施例2.5的方法制备LNP-EGFP-RNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入100ul(即2ug RNA)，并培养20小时，通过流式细胞仪(FACS)，检测F480+CD11b+细胞iNOS-APC的MFI，即为不同LNP的极化效果，结果如图6-1(流式散点图，由Flowjo分析软件生成)和图6-2所示，在BMDM中极化效果较好，其中LNP 37、38号最好。
实施例2.11：LNP将M2-BMDM细胞极化成为M0型
1、按照实施例2.7的方法(步骤1-13)获得成熟的BMDM细胞。
2、向DMEM完全培养基中加入20ng/mLIL-4，配置成M2型巨噬细胞培养基。
3、将成熟的BMDM细胞在M2型培养基中培养48h，获得M2型BMDM 
4、将选择43号LNP和37号LNP按照实施例2.5的方法制备LNP-EGFP-mRNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，向6孔板中成熟的BMDM每孔加入100ul(即2ug RNA)，并培养20小时，获得EGFP-BMDM。
5、将六孔板一个孔的EGFP-BMDM用刮刀刮下加入至六孔板中一个孔的M2型BMDM，共培养48h。
6、通过流式细胞仪(FACS)，检测F480+CD11b+细胞中M2型比例，结果如图7(流式图，flowjo流式分析软件生产)所示，43和37号两种LNP均将M2型巨噬细胞转化成为M0型。
实施例2.12：Raji细胞杀伤实验
1、按照实施例2.7的方法(步骤1-13)获得成熟的BMDM细胞。
2、将实施例2.7获得的43号LNP按照实施例2.5的方法制备LNP-CAR CD19-mRNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入100ul(即2ug RNA)，并培养20小时，获得CAR CD19-BMDM。
3、分别按照E/T为20:1,10:1,1:1,1:10,1:20向六孔板加入luc+Raji细胞，每孔终体积为1ml，阳性对照为只有Raji细胞且不加CAR-BMDM细胞，用培养基补足体积至1ml，阴性对照为BMDM细胞与Raji细胞共孵育，24h后取上清通过萤火虫荧光素酶报告基因检测试剂盒(yeasen，11404ES60)裂解细胞，酶标仪进行Raji细胞的荧光分析检测，杀伤比例计算公式：(阳性对照荧光强度-实验组荧光强度)/(阳性对照荧光强度-背景荧光强度)×100％；结果如图8-1活体图8-2所示，CAR CD19-BMDM能够杀伤Raji细胞。
实施例2.13：HER2+MC38细胞杀伤实验
1、按照实施例2.7的方法(步骤1-13)获得成熟的BMDM细胞。
2、将实施例2.7获得的43号LNP按照实施例2.5的方法制备LNP-CAR HER2-mRNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入100ul(即2ug RNA)，并培养20小时，获得CAR HER2-BMDM，并将其用刮刀刮下，铺于96孔板，每孔3*104细胞(即3*103CAR-BMDM)，铺板过夜；
3、分别按照E/T为20:1,10:1,5:1,2.5:1,1:2,1:10,1:20向96孔板加入luc+HER2+MC38细胞，每孔终体积为100ul，阳性对照为只有luc+HER2+MC38细胞且不加CAR-BMDM细胞，用培养基补足体积至100ul，阴性对照为BMDM细胞与Raji细胞共孵育，24h后通过萤火虫荧光素酶报告基因检测试剂盒(yeasen，11404ES60)裂解96孔板所有细胞，酶标仪进行细胞的荧光分析检测，杀伤比例计算公式：(阴性对照荧光强度-实验组荧光强度)/(阴性对照荧光强度-背景荧光强度)×100％；结果如图9所示，CAR HER2-BMDM能够杀伤HER2+MC38细胞。
实施例2.14：CAR-BMDM吞噬实验
1、按照实施例2.7的方法(步骤1-13)获得成熟的BMDM细胞。
2、将实施例2.7获得的43号LNP按照实施例2.5的方法制备LNP-CAR HER2-mRNA、LNP-CAR CD19-mRNA复合物，通过DMEM培养基稀释至RNA浓度为0.02ug/ul，每孔加入100ul(即2ug RNA)，并培养20小时，获得CAR HER2-BMDM和CAR CD19-BMDM；
3、按照E/T为1:3向6孔板加入EGFP+HER2+MC38细胞、EGFP+HER2+CT26细胞，每孔终体积为1ml，阴性对照为CAR CD19-BMDM细胞以及BMDM细胞与luc+HER2+MC38细胞、luc+HER2+CT26细胞共孵育，4h后通过流式细胞仪(FACS)，检测F480+CD11b+细胞EGFP+比例，即为CAR HER2-BMDM特异性吞噬比例，结果如图10所示。BMDM中发生吞噬作用的细胞比例在10％左右。
实施例2.15：LNP在野生型Balb/C小鼠体内靶向性探究
选择27、28、37、43、50号LNP按照实施例2.4的方法制备LNP-CAR HER2-luc-mRNA复合物，尾静脉注射20ug mRNA/mouse，6h后通过IVIS小动物活体成像系统来测定小鼠体内的生物荧光强度分布，以及解剖后的心肝脾肺肾骨髓的生物荧光强度分布；小鼠在成像前需先腹腔注射100μL的D-荧光素钾盐(30mg/mL，溶于PBS)。结果如图11-1、图11-2、图11-3所示，37号LNP主要分布在脾脏、肝脏部位，骨髓中也有信号，其余LNP荧光信号强度低于37号。
实施例2.16：LNP在野生型MC38肿瘤细胞荷瘤C57小鼠体内靶向
选择27、28、37、38、43号LNP按照实施例2.3的方法制备LNP-CAR HER2-luc-mRNA复合物，瘤内注射5ug mRNA/mouse，分别在6h、24h、48h通过IVIS小动物活体成像系统来测定小鼠 体内的生物荧光强度分布；小鼠在成像前需先腹腔注射100μL的D-荧光素钾盐(30mg/mL，溶于PBS)。结果如图12-1和图12-2所示，37号LNP在瘤内表达最高，稳定性最好。
实施例2.17：LNP在Cre转基因报告小鼠体内靶向性探究
选择37号LNP按照实施例2.4的方法制备LNP-Cre-mRNA复合物，尾静脉分别注射10ug、20ug mRNA/mouse，48h后通过流式细胞仪(FACS)，检测脾脏、骨髓细胞中Td tomato+细胞比例，即为37号LNP递送至体内何种免疫细胞。结果如图13-1和图13-2所示，37号LNP可以转染脾脏、骨髓中的多种免疫细胞细胞。
实施例2.18：LNP-mRNA递送系统体内构建原位CAR-myeliod验证
选择37号LNP按照实施例2.4的方法制备LNP-HER2-mRNA复合物，尾静脉注射20ug mRNA/mouse，24h后眼眶取血、取骨髓、脾脏，通过流式细胞仪(FACS)，检测CAR-HER2+免疫细胞分布。结果如图14所示，37号LNP可以原位生成CAR-免疫细胞，并随血液循环到达身体各处。
实施例2.19：原位CAR-免疫细胞疗法治疗肺转移模型
1、通过尾静脉注射过表达HER2抗原的luc+CT26肿瘤细胞，构建肺转移模型，来评价原位CAR-免疫细胞的体内抗肿瘤效果。将模型小鼠随机分为2组，每组5只小鼠用IVIS小动物活体成像系统来测定小鼠肺部的生物荧光强度，从而间接表示肿瘤的严重程度。小鼠在成像前需先腹腔注射100μL的D-荧光素钾盐(30mg/mL，溶于PBS)。
2、小鼠体重每两天测量一次，并绘制两组小鼠体重变化曲线如图15所示，治疗组小鼠体重明显高于对照组。选择37号LNP按照实施例2.4的方法制备LNP-HER2-mRNA复合物，尾静脉注射20ug mRNA/mouse，每隔4天给药一次，一共给6次药。通过肿瘤的生物荧光成像来监测肿瘤的生长，如图16所示。小鼠肺部肿瘤荧光半定量分析结果显示，在治疗的第17天，经LNP-CAR mRNA治疗的小鼠肺部的荧光强度明显比对照组要弱，如图17所示，证明其良好的肿瘤抑制效果。治疗组小鼠与对照组小鼠的生存曲线也存在明显差异，如图18所示，也证明了该疗法具有良好的治疗效果。
实施例2.20：原位CAR-免疫细胞疗法治疗实体瘤
1、通过皮下接种过表达HER2抗原的CT26肿瘤细胞，构建实体瘤模型，来评价原位CAR-免疫细胞的抗实体瘤效果。将模型小鼠随机分为实验组和对照组，每组9只小鼠。
2、小鼠的体重和肿瘤大小每两天测量一次，并绘制两组小鼠的体重变化曲线(如图19所示)和肿瘤大小变化曲线(如图20所示)；肿瘤大小使用游标卡尺测量其长(L)和宽(W)，肿瘤大小计算公式为：1/2×L×W2。
3、选择37号LNP按照实施例2.4的方法制备LNP-HER2-mRNA复合物，尾静脉注射20ug mRNA/mouse，每隔4天给药一次，一共给5次药。在治疗的第10天，经LNP-CAR mRNA治疗的小鼠已有两只出现肿瘤消退，在治疗的第13天，二组之间的重量大小出现差异(如图20所示)，证明了该疗法具有良好的治疗效果。
4、从小鼠体重来看，长期给药并没有造成体重下降；AST检测也证明了LNP的没有造成肝损伤(如图21所示)。
5、免疫组化结果可见，实验组小鼠Ki67表达明显低于对照组，证明肿瘤细胞增值能力下降，而CD3、巨噬细胞(F480)比例明显增多，CAR-免疫细胞免疫治疗发挥作用(如图22所示)。
实施例2.21：原位CAR-免疫细胞疗法治疗实体瘤的免疫细胞分型
1、将实施例2.20的实验组、对照组小鼠中各随机选择4只，将肿瘤剪下；
2、将待剪碎处理的肿瘤置于1.5ml EP管中，加入200ul组织裂解液(瑞沃德)，使用剪刀剪碎，直至1ml枪吹吸基本无阻碍为止；
3、剪碎后补充至2ml，用巴氏管转移至研磨机器管中，再加入1ml组织裂解液，使用组织研磨机器研磨
4、研磨结束后通过0.45um滤膜过滤，转移至15ml离心管中，400g离心5min；弃上清加入6ml裂红液，冰上裂解5min；随后400g离心5min弃上清；
6、加入6ml DMEM重悬，400g离心5min弃上清，DMEM培养基重悬，获得单细胞悬液；
7、通过流式细胞术检测了37号LNP治疗对肿瘤免疫微环境重编程的影响。根据流式分析结果，治疗组的M2巨噬细胞(CD206+)浸润减少(图23)，这个结果证明肿瘤微环境中的促肿瘤的巨噬细胞发生了表型转移。在CD4+T细胞流式分析中我们发现，治疗组的肿瘤微环境中的Tfh细胞、Th1浸润增多(图24)，在CD8+T细胞流式分析中，proliferating CD8+T cells(Ki67+)、perforin T细胞的百分比也明显增加(图25)。综上所述，37号LNP递送CAR mRNA原位生成CAR-免疫细胞的治疗策略增加了增强了细胞毒性T细胞活性，改变了肿瘤免疫微环境。
实施例2.22：LNP在体内递送环状RNA 
1、将按照实施例2.2制备的43号LNP置于透析袋(3.5K，Thermo Scientific)、超纯水室温透析3h以上；透析后的LNP浓度在0.8-1ug/ul之间。将LNP与环状luc RNA LNP按照质量比为10:1混合孵育15min，通过15ml 50KDa超滤离心管5000g浓缩，获取进行瘤内注射的复合物，体积在30-50ul/mouse。
2、瘤内注射复合物5ug mRNA/mouse，分别在24h、48h、72h通过IVIS小动物活体成像系统来测定小鼠体内的生物荧光强度分布；小鼠在成像前需先腹腔注射100μL的D-荧光素钾盐(30mg/mL，溶于PBS)。结果如图26所示，43号LNP也可以递送环状RNA。
尽管以上结合对本申请的实施方案进行了描述，但本申请并不局限于上述的具体实施方案和应用领域，上述的具体实施方案仅仅是示意性的、指导性的，而不是限制性的。本领域的普通技术人员在本说明书的启示下和在不脱离本申请权利要求所保护的范围的情况下，还可以做出很多种的形式，这些均属于本申请保护之列。

Claims (55)

  1. 一种式(I)的化合物：
    或其药学上可接受的盐、前药或立体异构体，其中：
    所述G1和G2各自独立地为任选地取代的C2-C24直链亚烷基；
    所述L1和L2各自独立地为-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)x-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRaC(＝O)-、-C(＝O)NRb-、-NRaC(＝O)NRb-、-OC(＝O)NRb-、-NRaC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORb)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；
    Ra和Rb各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；
    x是0、1或2；
    所述G3和G4各自独立地为键、任选地取代的C2-C24直链亚烷基；
    所述L3和L4各自独立地为键、-OC(＝O)-、-C(＝O)O-、-OC(＝O)O-、-C(＝O)-、-O-、-S(O)i-、-SS-、-C(＝O)S-、-SC(＝O)-、-NRcC(＝O)-、-C(＝O)NRc-、-NRcC(＝O)NRd-、-OC(＝O)NRc-、-NRcC(＝O)O-、-SC(＝S)-、-C(＝S)S-、-C(＝S)-、-CH(OH)-、-P(＝O)(ORc)O-、-(C6-C10亚芳基)-或-(6至10元亚杂芳基)-；
    Rc和Rd各自独立地为H、任选地取代的C1-C12烷基或任选地取代的C1-C12烯基；
    i是0、1或2；
    所述G5和G6各自独立地为任选地取代的C2-C24直链烷基、任选地取代的C2-C24直链烯基；
    所述Z为任选地取代的C1-C12亚烷基、任选地取代的-ReG7Rf-；
    其中，Re和Rf为任选地取代的C1-C12亚烷基；
    G7为-NRg-、-(3-7元饱和环亚烷烃)-、-(3-7元杂环亚烷烃)-、-(3-7元环状亚芳基)-或-(3-7元环状亚杂芳基)-；
    Rg为任选地取代的C1-C12亚烷基；
    所述X和Y各自独立地为任选地取代的C1-C12直链烷基、-G1L1G3L3G5或X、Z连同其所连接的氮成环。
  2. 根据权利要求1所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A)所示的结构：
    其中，G1、G2、G3、G4、G5、G6、L1、L2、L3、L4、X和Y如权利要求1中所定义；
    G8为任选地取代的C1-C12亚烷基。
  3. 根据权利要求1所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B)所示的结构：
    其中，G1、G2、G3、G4、G5、G6、G7、L1、L2、L3、L4、Re、Rf、X和Y如权利要求1中所定义。
  4. 根据权利要求1至3中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G1和G2是未被取代的C2-C4亚烷基。
  5. 根据权利要求1至4中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中L1和L2是-C(＝O)O-。
  6. 根据权利要求1至5中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G3和G4为键。
  7. 根据权利要求1至5中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G3和G4为未被取代的C2-C4亚烷基。
  8. 根据权利要求1至6中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中L3和L4为键。
  9. 根据权利要求1-5、7中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中L3和L4是-OC(＝O)O-。
  10. 根据权利要求1至9中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，G5和G6为任选地取代的C4-C16直链烯基。
  11. 根据权利要求2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-1)所示的结构：
    其中，m为1或3，n为0或1，G5和G6的定义如权利要求10所定义，G8为权利要求2所定义，G9和G10为任选地取代的C1-C5直链烷烃。
  12. 根据权利要求2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-2)所示的结构：

    其中，m为1或3，n为0或1，G5和G6的定义如权利要求10所定义。
  13. 根据权利要求2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-3)所示的结构：
    其中，m为1或3，n为0或1，G5和G6的定义如权利要求10所定义。
  14. 根据权利要求2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-A-4)所示的结构：
    其中，G1、G2、G3、G4、G5、G6、L1、L2、L3、L4和Y的定义如权利要求1中所定义；G8为任选地取代的C1-C12亚烷基。
  15. 根据权利要求2、4-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，所述化合物具有式(I-A-5)所示的结构：
    其中，m为1或3，n为0或1，Y、G5和G6的定义如权利要求1中所定义；G8为任选地取代的C1-C12亚烷基。
  16. 根据权利要求2、4-10中任一项所述的用途，或其药学上可接受的盐、前药或立体异构体，所述化合物具有式(I-A-6)所示的结构：
    其中，m为1或3，n为0或1，Y、G5和G6的定义如权利要求1中所定义。
  17. 根据权利要求3-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B-1)所示的结构：
    其中，m为1或3，n为0或1，G5和G6的定义如权利要求10所定义。
  18. 根据权利要求3-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B-2)所示的结构：
    其中，m为1或3，n为0或1，G5和G6的定义如权利要求10所定义。
  19. 根据权利要求3-10中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，所述化合物具有式(I-B-3)所示的结构：
    其中，m为1或3，n为0或1，G5和G6的定义如权利要求10所定义。
  20. 根据权利要求3-10中任一项所述的用途，或其药学上可接受的盐、前药或立体异构体，所述化合物具有式(I-B-4)所示的结构：
    其中，G1、G2、G3、G4、G5、G6、G7、L1、L2、L3、L4、Re和Rf如权利要求1中所定义。
  21. 根据权利要求2、4-11中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其 特征在于，其中G8为任选地取代的C2-C4亚烷基。
  22. 根据权利要求2、4-11中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其特征在于，其中G9或G10或两者具有以下结构之一：甲基、乙基、2-羟基乙基。
  23. 根据权利要求1至22中任一项所述的化合物，其中G5或G6或两者具有以下结构之一：
  24. 根据权利要求1至23中任一项所述的化合物，或其药学上可接受的盐、前药或立体异构体，其为如下化合物：







  25. 一种组合物，其包含：治疗剂或预防剂；以及用于递送所述治疗剂或预防剂的载体，其中，所述载体包括阳离子脂质，所述阳离子脂质包括权利要求1至24中任一项所述的式(I)所示的化合物、或其药物可用的盐中的一种或多种。
  26. 根据权利要求25所述的组合物，其中所述治疗剂或预防剂选自核酸分子、小分子化合物、多肽或蛋白质中的一种或多种，优选，其中所述核酸分子选自单链DNA、双链DNA、短异构体、agomir、 antagomir、反义分子、小干扰RNA(siRNA)、不对称干扰RNA(aiRNA)、microRNA(miRNA)、Dicersubstrate RNA(dsRNA)、小发夹RNA(shRNA)、转移RNA(tRNA)、信使RNA(mRNA)、锁核酸(LNA)、肽核酸(PNA)或吗啉环寡聚核苷酸中的一种或多种。
  27. 根据权利要求26所述的组合物，所述治疗剂或预防剂包含至少一种编码抗原或其片段或表位的mRNA优选，所述的mRNA是单顺反子mRNA或多顺反子mRNA。
  28. 根据权利要求27所述的组合物，所述的抗原是病原性抗原。
  29. 根据权利要求26所述的组合物，所述mRNA包含一种或多种功能性核苷酸类似物，所述功能性核苷酸类似物选自假尿嘧啶核苷、1-甲基-假尿嘧啶核苷或5-甲基胞嘧啶中的一种或多种。
  30. 根据权利要求25，所述小分子化合物选自抗肿瘤药、抗感染药、局部麻醉药、抗抑郁药、抗惊厥药、抗生素/抗菌剂、抗真菌药、抗寄生虫药、激素、激素拮抗剂、免疫调节剂、神经递质拮抗剂、抗青光眼剂、麻醉剂或成像剂中的一种或多种。
  31. 根据权利要求25所述的组合物，所述载体与所述治疗或预防剂的质量比为5：1～50：1。
  32. 根据权利要求25所述的组合物，所述组合物为纳米颗粒制剂，所述纳米颗粒制剂的平均尺寸为10～500nm；或者；所述纳米颗粒的pKa为4.5～8.5。
  33. 根据权利要求25至32中任一项所述的组合物，其中，所述载体进一步包含或一种或多种中性脂质。
  34. 根据权利要求33所述的组合物，其中所述中性脂质为选自磷脂酰胆碱、磷脂酰乙醇胺、鞘磷脂、神经酰胺、甾醇及其衍生物中的一种或多种。
  35. 根据权利要求25至34中任一项所述的组合物，其中阳离子脂质与所述中性脂质的摩尔比为100：1～5:1。
  36. 根据权利要求25至32中任一项所述的组合物，其进一步包含类固醇，优选，所述类固醇为选自胆固醇、非甾醇、谷固醇、麦角固醇、菜油甾醇、豆甾醇、芸苔甾醇、番茄碱、番茄碱、熊果酸、α-生育酚、皮质类固醇中的一种或多种。
  37. 根据权利要求25至36中任一项所述的组合物，其中阳离子脂质与所述类固醇的摩尔比为2:1～4:1。
  38. 根据权利要求25至36中任一项所述的组合物，其中所述组合物进一步包含一种或多种能够与聚合物结合的脂质，优选，所述能够与聚合物结合的脂质为选自PEG修饰的磷脂酰乙醇胺、PEG修饰的磷脂酸、PEG修饰的神经酰胺、PEG修饰的二烷基胺、PEG修饰的二酰基甘油或PEG修饰的二烷基甘油中的一种或多种，进一步优选，其中所述阳离子脂质与所述能够与聚合物结合的脂质的摩尔比为100:1～20:1。
  39. 根据权利要求25至36中任一项所述的组合物，所述载体还包括中性脂质、结构脂质以及聚合物共轭脂质，所述阳离子脂质、所述中性脂质、所述类固醇脂质、以及所述聚合物共轭脂质的摩尔比为(15～70)：(1～15):(15～55):(0～3)。
  40. 根据权利要求25所述的组合物，其特征在于，所述的组合物还包括药物可用的赋形剂，优选，所述的赋形剂包括药物可用的稀释剂。
  41. 一种如权利要求1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或权利要求25至40中任一项所述的组合物在在制备药物中的应用，优选所述药物为选自基因药物、核酸疫苗、小分子药物、多肽或蛋白质药物中的任一种。
  42. 一种如权利要求1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或权利要求25至40中任一项所述的组合物在靶向免疫细胞中的用途。
  43. 一种如权利要求1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或权利要求25至40中任一项所述的组合物在制备靶向免疫细胞的药物中的用途。
  44. 根据权利要求42或43所述的用途，其中，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞。
  45. 一种如权利要求1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或权利要求25至40中任一项所述的组合物在促进细胞极化中的用途。
  46. 一种如权利要求1～24中任一项所述的式(I)所示的化合物、或其药学上可接受的盐、前药或立体异构体，或权利要求25至40中任一项所述的组合物在制备促进免疫细胞极化的药物中的用途。
  47. 根据权利要求45或46所述的用途，其中，所述细胞极化为由M0型向M1型极化。
  48. 根据权利要求45或46所述的用途，其中，所述细胞极化为由M2型向M0型极化。
  49. 根据权利要求45或46所述的用途，其中，所述细胞为巨噬细胞。
  50. 一种体外筛选脂质纳米颗粒的方法，其包括：
    在巨噬细胞细胞系中进行第一次筛选，获得可以转染巨噬细胞细胞系的脂质纳米颗粒；
    在获得的脂质纳米粒颗粒中选择FLuc荧光信号强度高于10000RLUs的脂质纳米粒颗粒在骨髓来源的原代巨噬细胞中进行第二次筛选；
    第二次筛选后获得目标脂质纳米颗粒。
  51. 根据权利要求50所述的方法，其中，所述巨噬细胞细胞系为Raw264.7细胞系。
  52. 一种筛选适用于体内免疫细胞mRNA递送的脂质纳米粒颗粒的方法，其包括：
    将包裹携带报告基因的CAR-mRNA的脂质纳米粒颗粒经尾静脉注射入野生型小鼠，筛选获得在给定器官有表达且表达比例高于80％的第一脂质纳米粒颗粒；
    任选的，将筛选获得第一脂质纳米粒颗粒包裹携带报告基因的CAR-mRNA，瘤内注射荷瘤小鼠，筛选获得只在肿瘤部位表达，其他器官不表达，且稳定表达24～48h的第二脂质纳米粒颗粒；
    将筛选获得第一或第二脂质纳米粒颗粒经尾静脉注射入Cre报告基因小鼠，筛选获得在免疫细胞具有Td tomato+细胞的目标脂质纳米粒颗粒。
  53. 根据权利要求50所述的方法，其中，所述给定器官选自脾脏或骨髓。
  54. 根据权利要求50所述的方法，其中，所述免疫细胞选自淋巴细胞、树突状细胞、巨噬细胞、粒细胞、肥大细胞中的任意一种。
  55. 根据权利要求50-54中任一项所述的方法，其中，所述目标脂质纳米颗粒为权利要求1-24中涉及的式(I)的化合物或其药学上可接受的盐、前药或立体异构体所制备得到。
PCT/CN2024/105654 2024-02-05 2024-07-16 一种新型脂质化合物以及组合物和核酸脂质纳米颗粒制剂及其筛选方法和应用 Pending WO2025166993A1 (zh)

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