Lipid nanoparticles for delivery of aminolipid compounds and biologically active ingredients

Abstract

Provided are amino lipid compounds for preparing lipid nanoparticles for delivering active ingredients, a method for preparing the same, lipid nanoparticles containing the amino lipid compounds, and pharmaceutical compositions, as well as uses thereof.

Description

[Technical Field]

[0001] The present disclosure relates to amino lipid compounds that can be used to prepare lipid nanoparticles for delivering active ingredients, and methods for preparing the same. The present disclosure also relates to lipid nanoparticles and pharmaceutical compositions containing the amino lipid compounds, and uses thereof. [Background technology]

[0002] Safe and effective targeted delivery of biologically active substances (e.g., nucleic acids, proteins, small molecule drugs, etc.) to cells, tissues, or organs remains a technical challenge in the field of drug delivery, especially for nucleic acid drugs, which are vulnerable to degradation by nucleases in plasma. Nucleic acid drugs (e.g., mRNA, antisense oligonucleotides (ASOs), microRNAs (miRNAs), small interfering RNAs (siRNAs), and aptamers) are gradually being developed as new therapeutic approaches and hold great therapeutic potential in cancer treatment, infection prevention, and genetic disease treatment. Lipid nanoparticle delivery of nucleic acid drugs has been widely used. However, there is room for further improvement in the targeting, safety, and delivery efficiency of nucleic acid drug delivery systems. Different lipid nanoparticles with different properties must be appropriately selected for different nucleic acid drugs, cells (or tissues, organs), and application scenarios. Therefore, there is a strong demand for the development of various lipid nanoparticles, especially amino lipid compounds for preparing lipid nanoparticles, to address the needs of nucleic acid drug delivery in various application scenarios. Summary of the Invention

[0003] Summary of the Invention In one aspect of the present disclosure, there is provided an amino lipid compound represented by formula (I): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1, and R2 are each defined below.

[0004] In another aspect of the present disclosure, there is provided a method for preparing the amino lipid compounds. In another aspect of the present disclosure, there is provided the use of the amino lipid compounds described above in the manufacture of a vehicle for an active ingredient. In another aspect of the present disclosure, there is provided a lipid nanoparticle comprising the amino lipid compound. In another aspect of the present disclosure, there is provided a pharmaceutical composition comprising the lipid nanoparticles described above. In another aspect of the present disclosure, there is provided a method for delivering a bioactive ingredient to a cell, tissue, or organ using the lipid nanoparticle or the pharmaceutical composition. In another aspect of the present disclosure, there is provided a method for producing a polypeptide and / or protein of interest in mammalian cells using the lipid nanoparticles or the pharmaceutical composition. In another aspect of the present disclosure, there is provided a use of the amino lipid compound, the lipid nanoparticle, or the pharmaceutical composition in the manufacture of a medicament. In another aspect of the present disclosure, there is provided a method for preventing and / or treating a disease or disorder in a mammal in need thereof with said lipid nanoparticles or said pharmaceutical composition. In another aspect of the present disclosure, there is provided a use of the amino lipid compound, the lipid nanoparticle, or the pharmaceutical composition in the manufacture of a pharmaceutical for nucleic acid transfer. [Brief explanation of the drawings]

[0005] [Figure 1] 1 shows the results of an in vivo safety (ALT enzyme activity) test of lipid nanoparticles containing different amino lipid compounds. [Figure 2] 1 shows the results of an in vivo safety (ALT enzyme activity) test of lipid nanoparticles containing different amino lipid compounds. [Figure 3] 1 shows the results of in vivo safety (AST enzyme activity) testing of lipid nanoparticles containing different amino lipid compounds. [Figure 4] 1 shows the results of in vivo safety (AST enzyme activity) testing of lipid nanoparticles containing different amino lipid compounds. [Figure 5] 1 shows the in vivo delivery results of lipid nanoparticles containing different amino lipid compounds. [Figure 6] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations within the spleen. [Figure 7] 1 shows the delivery efficiency of lipid nanoparticles containing different amino lipid compounds in different immune cell populations of PBMCs. DETAILED DESCRIPTION OF THE INVENTION

[0006] Detailed Description of the Invention definition Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as commonly understood by those skilled in the art. References to technology used herein are intended to mean technology commonly understood in the art, including variations or equivalent technology substitutes that are obvious to those skilled in the art. Although the following terms are believed to be well understood by those skilled in the art, the following definitions are provided to better explain this disclosure.

[0007] As used herein, the terms "comprising," "including," "having," "containing," or "involving," and other variations thereof, are inclusive or open-ended and do not exclude other, unrecited elements or method steps.

[0008] As used herein, the term "hydrocarbyl" refers to the group remaining after losing one hydrogen atom from an aliphatic hydrocarbon, and includes straight-chain or branched, saturated or unsaturated hydrocarbyl. Hydrocarbyl groups include, but are not limited to, alkyl, alkenyl, and alkynyl. Preferably, the hydrocarbyl group contains 1 to 24 carbon atoms (C1-C 24hydrocarbyl), for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 carbon atoms (C1, C2, C3, ... C 21 , C 22 , C 23 , or C 24 Examples of hydrocarbyl groups include C-C 24 Hydrocarbyl, C1-C 22 Hydrocarbyl, C1-C 20 Hydrocarbyl, C1-C 18 Hydrocarbyl, C1-C 16 Hydrocarbyl, C1-C 12 Hydrocarbyl, C1-C 10 Hydrocarbyl groups include, but are not limited to, hydrocarbyl, C1-C8 hydrocarbyl, C1-C7 hydrocarbyl, C1-C6 hydrocarbyl, C1-C4 hydrocarbyl, C1-C3 hydrocarbyl, C1-C2 hydrocarbyl, C2-C8 hydrocarbyl, C2-C4 hydrocarbyl, C4-C8 hydrocarbyl, C4-C9 hydrocarbyl, C5-C8 hydrocarbyl, C1-C4 hydrocarbyl, C2-C8 hydrocarbyl, C3 hydrocarbyl, C4 hydrocarbyl, C5 hydrocarbyl, C6 hydrocarbyl, C7 hydrocarbyl, and C8 hydrocarbyl. Unless expressly stated otherwise herein, hydrocarbyl groups are optionally substituted, and the substituents are referred to below in the definition of "optionally substituted." In certain embodiments, the hydrocarbyl group has no branches (i.e., is linear), one branch, two branches, or multiple branches.

[0009] As used herein, the term "hydrocarbylene" refers to the divalent group remaining after losing one hydrogen atom from hydrocarbyl, as defined above. Unless expressly stated otherwise in the specification, hydrocarbylene groups are also optionally substituted.

[0010] As used herein, the term "alkyl" refers to a linear or branched, saturated, monovalent hydrocarbyl. Preferably, an alkyl group contains 1 to 24 carbon atoms (C1-C 24 alkyl), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 carbon atoms (C1, C2, C3, ... C 21 , C 22 , C 23 , or C 24 Examples of alkyl groups include C1-C 24 Alkyl, C1-C 22 Alkyl, C1-C 20 Alkyl, C1-C 18 Alkyl, C1-C 16 Alkyl, C1-C 12 Alkyl, C1-C 10 Examples of alkyl groups include, but are not limited to, alkyl, C1-C8 alkyl, C1-C7 alkyl, C1-C6 alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, C2-C8 alkyl, C2-C4 alkyl, C4-C8 alkyl, C4-C9 alkyl, C5-C8 alkyl, C1-C4 alkyl, C2-C8 alkyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, and tridecane-7-yl. Unless otherwise specified explicitly in the specification, alkyl groups are optionally substituted.

[0011] As used herein, the term "alkylene" refers to the divalent group remaining after losing one additional hydrogen atom from an alkyl, as defined above. Unless expressly stated otherwise in the specification, alkylene is also optionally substituted.

[0012] As used herein, the term "alkenyl" refers to a straight or branched chain monovalent hydrocarbyl containing one or more double bonds (C=C). Preferably, an alkenyl group contains 2 to 24 carbon atoms (C-C 24alkenyl), for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 carbon atoms (C2, C3, C4, ... C 21 , C 22 , C 23 , or C 24 alkenyl) and having 1, 2, 3, 4, or more double bonds. Examples of alkenyl groups include C-C 24 Alkenyl, C2-C 22 Alkenyl, C2-C 20 Alkenyl, C2-C 18 Alkenyl, C2-C 16 Alkenyl, C2-C 12 Alkenyl, C2-C 10 Examples of alkenyl include, but are not limited to, alkenyl, C2-C8 alkenyl, C2-C7 alkenyl, C2-C6 alkenyl, C2-C4 alkenyl, C2-C3 alkenyl, C4-C8 alkenyl, C4-C9 alkenyl, and C5-C8 alkenyl. Some more specific examples include, but are not limited to, ethenyl, propenyl, but-1-enyl, but-2-enyl, pent-1-enyl, pent-2-enyl, hex-1-enyl, hex-2-enyl, hex-3-enyl, hept-1-enyl, hept-2-enyl, hept-3-enyl, oct-1-enyl, oct-2-enyl, oct-3-enyl, non-1-enyl, non-2-enyl, and non-3-enyl. In some preferred embodiments, the alkenyl group has one double bond. Unless stated otherwise explicitly in the specification, an alkenyl group is optionally substituted.

[0013] As used herein, the term "alkenylene" refers to the divalent group remaining after losing one additional hydrogen atom from the alkenyl defined above. Unless expressly stated otherwise in the specification, the alkenylene group is optionally substituted.

[0014] As used herein, the term "alkynyl" refers to a linear or branched monovalent alkynyl group containing one or more triple bonds (C≡C). Preferably, the alkynyl group contains 2 to 24 carbon atoms (C-C 24 alkynyl), for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 carbon atoms (C2, C3, C4, ... C 21 , C 22 , C 23 , or C 24 Alkynyl groups include C2-C3 alkyl groups having one, two, three, four, or more triple bonds. 24 Alkynyl, C2-C 22 Alkynyl, C2-C 20 Alkynyl, C2-C 18 Alkynyl, C2-C 16 Alkynyl, C2-C 12 Alkynyl, C2-C 10 Examples of alkynyl include, but are not limited to, alkynyl, C2-C8 alkynyl, C2-C7 alkynyl, C2-C6 alkynyl, C2-C4 alkynyl, C2-C3 alkynyl, C4-C8 alkynyl, C4-C9 alkynyl, and C5-C8 alkynyl. Some more specific examples include, but are not limited to, ethynyl, propynyl, but-1-ynyl, but-2-ynyl, pent-1-ynyl, pent-2-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hept-1-ynyl, hept-2-ynyl, hept-3-ynyl, oct-1-ynyl, oct-2-ynyl, oct-3-ynyl, non-1-ynyl, non-2-ynyl, and non-3-ynyl. In some embodiments, the alkynyl group has one triple bond. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted.

[0015] As used herein, the term "alkynylene" refers to the divalent group remaining after losing one additional hydrogen atom from the alkynyl defined above. Unless otherwise expressly stated in the specification, the alkynylene group is optionally substituted.

[0016] As used herein, the terms "cyclohydrocarbyl," "cyclohydrocarbylene," and "hydrocarbon ring" refer to saturated (i.e., "cycloalkyl" and "cycloalkylene") or unsaturated (i.e., having one or more double bonds (cycloalkenyl) and / or triple bonds (cycloalkynyl) in the ring), monocyclic or polycyclic hydrocarbon rings having ring carbon atoms. In certain embodiments, "cyclohydrocarbyl," "cyclohydrocarbylene," and "hydrocarbon ring" have, for example, 3 to 10, suitably 3 to 8, more suitably 3 to 6, e.g., 5 to 6, or 5 to 7 ring carbon atoms. "Cyclohydrocarbyl," "cyclohydrocarbylene," and "hydrocarbon ring" include, but are not limited to, cyclopropyl(ren)(ring), cyclobutyl(ren)(ring), cyclopentyl(ren)(ring), cyclohexyl(ren)(ring), cycloheptyl(ren)(ring), cyclooctyl(ren)(ring), cyclononyl(ren)(ring), cyclohexenyl(ren)(ring), and the like. Unless expressly stated otherwise in this specification, cyclohydrocarbyl, cyclohydrocarbylene, and hydrocarbon rings are optionally substituted.

[0017] As used herein, the term "cycloalkyl" refers to a saturated monocyclic or polycyclic (e.g., bicyclic) hydrocarbon ring (e.g., monocyclic such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, or bicyclo[5.2.0]nonyl, spirocyclic such as decalin, bicyclic, fused, or bridged systems, etc.). In certain embodiments, cycloalkyl groups have, for example, 3 to 10, e.g., 3 to 7, 5 to 6, or 5 to 7 carbon atoms. Unless expressly stated otherwise in the specification, cycloalkyl groups are optionally substituted.

[0018] As used herein, the term "heterohydrocarbyl" or any subclass thereof (e.g., heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, etc.) refers to a stable linear, branched, or cyclic hydrocarbon radical or combination thereof consisting of the specified number of carbon atoms and at least one heteroatom. A heteroatom is an atom other than carbon or hydrogen. In certain embodiments, a heterohydrocarbyl group contains one, two, or more heteroatoms. In certain embodiments, a heterohydrocarbyl group contains one or more of the same or different heteroatoms. Preferably, the heteroatom is selected from O, N, and S. Examples of heterohydrocarbyl groups include, but are not limited to, -CH-CH-O-CH, -CH-CH-CH-O-CH-CH, -CH-(CH)-O-(CH)-CH, -CH-CH-NH-CH, -CH-CH-N(CH)-CH, -CH-S-CH-CH, -CH-CH, -CH=CH-O-CH, -CH-CH=N-OCH, -CH=CH-N(CH)-CH, and -CH-NH-OCH. Unless stated otherwise explicitly in the specification, heterohydrocarbyl groups are optionally substituted.

[0019] As used herein, the term "heterohydrocarbylene" or its sub-concepts (heteroalkylene, heteroalkenylene, heteroalkynylene, heteroarylene, etc.) refers to the divalent group remaining after losing one additional hydrogen atom from the heterohydrocarbyl defined above. Unless otherwise expressly stated in this specification, "heterohydrocarbylene" or its sub-concepts (heteroalkylene, heteroalkenylene, heteroalkynylene, heteroarylene, etc.) are optionally substituted.

[0020] As used herein, the term "heterocycle," "heterocyclyl," or "heterocyclylene" refers to a cyclic group having a cyclic structure and containing one or more heteroatoms among the ring-forming atoms. In certain embodiments, the ring-forming atoms contain one or more heteroatoms, which may be the same or different. In certain embodiments, the one or more heteroatoms contained in the ring-forming atoms are selected from N, O, and S. A "heterocycle," "heterocyclyl," or "heterocyclylene" disclosed herein is saturated or unsaturated. In certain embodiments, a "heterocycle," "heterocyclyl," or "heterocyclylene" consists of a monocyclic ring, a bicyclic ring, or a polycyclic ring. In certain embodiments, a "heterocycle," "heterocyclyl," or "heterocyclylene" is a 4- to 10-membered heterocycle, for example, a 4- to 7-membered heterocycle or a 5- to 7-membered heterocycle. Preferably, in certain embodiments, the heterocyclic group is an optionally substituted 4- to 10-membered saturated heterocycle, wherein the ring-forming atoms contain 1, 2, 3, 4, 5, or 6 heteroatoms selected from N, O, and S. More preferably, the heterocyclic group is an optionally substituted 4- to 7-membered saturated heterocycle, wherein the ring-forming atoms contain 1, 2, 3, or 4 heteroatoms selected from N, O, and S; more preferably, the heterocyclic group is an optionally substituted 5- to 7-membered (e.g., 5- to 6-membered) saturated heterocycle, wherein the ring-forming atoms contain 1, 2, or 3 heteroatoms selected from N, O, and S. Examples of heterocycles include, but are not limited to, azetidine, oxetanyl, tetrahydrofuran, pyrrolidine, imidazolidine, pyrazolidine, tetrahydropyran, piperidine, morpholine, thiomorpholine, and piperazine, preferably pyrrolidine, piperidine, piperazine, and morpholine. A heterocycle may be optionally substituted with one or more substituents, the substituents of which are referred to below in the definition of "optionally substituted." Unless expressly stated otherwise in the specification, a heterocycle, heterocyclyl, or heterocyclylene is optionally substituted.

[0021] As used herein, the term "aryl" refers to an all-carbon monocyclic or fused polycyclic aromatic group having a conjugated π electron system. For example, as used herein, "C 6-14 The term "aryl" means an aromatic group containing 6 to 14 (e.g., 6 to 12) carbon atoms, such as phenyl or naphthyl. Unless stated otherwise specifically in the specification, an aryl group is optionally substituted.

[0022] As used herein, the term "heteroaryl" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) aromatic group whose ring atoms consist of carbon atoms and at least one heteroatom and have a conjugated π-electron system, e.g., 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 carbon atoms and 1, 2, 3, 4, or 5 identical or different heteroatoms independently selected from N, O, S, and S(O)2. One or more ring carbon atoms in a heteroaryl group may be substituted with C(O). The heteroaryl group may be benzofused. Unless otherwise expressly defined herein, the heteroaryl group is optionally substituted.

[0023] As used herein, the term "optionally substituted" means that one or more hydrogen atoms attached to an atom or group are independently unsubstituted or independently substituted with one or more (e.g., 1, 2, 3, or 4) substituents. Substituents may independently include deuterium (D), tritium (T), halogen, -OH, mercapto, cyano, -CD3, C1-C6 alkyl (preferably C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl (preferably C3-C8 cycloalkyl), aryl, heterocyclyl (preferably 3- to 8-membered heterocyclyl), heteroaryl, arylC1-C6 alkyl-, heteroarylC1-C6 alkyl, C1-C6 haloalkyl, -OC1-C6 alkyl (preferably -OC1-C3 alkyl), -OC2-C6 alkenyl, OC1-C6 alkylphenyl, C1-C6 alkyl-OH (preferably C1-C4 alkyl-OH), C1-C6 alkynyl, alkyl, -SH, C1-C6 alkyl-O—C1-C6 alkyl, O-C1-C6 haloalkyl, NH2, C1-C6 alkyl-NH2 (preferably C1-C3 alkyl-NH2), —N(C1-C6 alkyl)2 (preferably —N(C1-C3 alkyl)2), —NH(C1-C6 alkyl) (preferably —NH(C1-C3 alkyl)), —N(C1-C6 alkyl)(C1-C6 alkylphenyl), —NH(C1-C6 alkylphenyl), nitro, —C(O)—OH, —C(O)OC1-C6 alkyl (preferably —C(O)OC1-C3 alkyl), —CONRiRii (wherein Ri and / or Ri are H, D and C1-C6 alkyl, preferably C1-C3 alkyl).), —NHC(O)(C1-C6 alkyl), —NHC(O)(phenyl), —N(C1-C6 alkyl)C(O)(C1-C6 alkyl), —N(C1-C6 alkyl)C(O)(phenyl), —C(O)C1-C6 alkyl, —C(O)heteroaryl (preferably —C(O)-5- to 7-membered heteroaryl), —C(O)C1-C6 alkylphenyl, —C(O)C1-C6 haloalkyl, —OC(O)C1-C6 alkyl (preferably —OC(O)C1-C3 alkyl), —S( and -NHS(O)-Ci-C6 alkyl, -S(O)-Ci-C6 alkyl, -S(O)-phenyl, -S(O)-Ci-C6 haloalkyl, -S(O)2NH2, -S(O)2NH(Ci-C6 alkyl), -S(O)2NH(phenyl), -NHS(O)2(Ci-C6 alkyl), -NHS(O)2(phenyl) and -NHS(O)2(Ci-C6 haloalkyl), wherein each of alkyl, cycloalkyl, phenyl, aryl, heterocyclyl, and heteroaryl is further halogen, -OH, -NH2, cycloalkyl, 3- to 8-membered heterocyclyl, C1-C4 alkyl, C1-C4 haloalkyl-, -OC1-C4 alkyl, -C1-C4 alkyl-OH, -C1-C4 alkyl-O-C1-C4 alkyl, -OC1-C4 haloalkyl, cyano, nitro, -C(O)-OH, -C(O)OC1-C6 alkyl, -CON(C1-C6 alkyl)2, -CONH(C1-C6 alkyl), -CONH2, -NHC(O)(C1-C6 alkyl), -NH(C1

[0023] The substituents are optionally substituted with one or more substituents selected from, but not limited to, -C6 alkyl)C(O)(C1-C6 alkyl), -SO2(C1-C6 alkyl), -SO2(phenyl), -SO2(C1-C6 haloalkyl), -SONH2, -SONH(C1-C6 alkyl), -SONH(phenyl), -NHSO2(C1-C6 alkyl), -NHSO2(phenyl), and -NHSO2(C1-C6 haloalkyl). When an atom or group is substituted with multiple substituents, the multiple substituents may be the same or different.

[0024] In certain embodiments, the substituents are independently selected from halogen (e.g., chlorine, bromine, fluorine, iodine), carboxylic acid (e.g., —C(═O)—OH), oxygen (e.g., ═O), sulfur (e.g., ═S), hydroxyl (e.g., —OH), ester group (e.g., —C(═O)OR or —OC(═O)R), aldehyde group (e.g., —C(═O)H), carbonyl (e.g., represented by —C(═O)R or C═O), acyl halide (e.g., —C(═O)X, where X is bromine, fluorine, chlorine, or iodine), carboxylic acid ester group (e.g., —OC(═O)OR), alkoxy group (e.g., —OR), acetal (e.g., —C(OR)R, where each OR is the same or different and is an alkoxy group), phosphate (e.g., P(═O) 3- ), thiol (e.g., -SH), sulfoxide (e.g., -S(=O)Riii), sulfinic acid (e.g., -S(=O)OH), sulfonic acid (e.g., -S(=O)2OH), thioaldehyde (e.g., -C(=S)H), sulfate (e.g., S(=O)4 2-), sulfonyl (e.g., -S(=O)R), sulfinyl (e.g., -S(=O)R), amido group (e.g., -C(=O)N(R) or -N(R)C(=O)R), azido (e.g., -N), nitro (e.g., -NO), cyano (e.g., -CN), isocyano (e.g., -NC), acyloxy (e.g., -OC(=O)R), amino (e.g., -N(R), -N(R)H, or -NH), carbamoyl (e.g., -OC(=O)N(R), -OC(=O), )N(Riii)H, or -OC(=O)NH2), sulfonamide groups (e.g., -S(=O)2N(Riii)2, -S(=O)2N(Riii)H, -S(=O)2NH2, -N(Riii)S(=O)2Riii, -N(H)S(=O)2Riii, -N(Riii)S(=O)2H, or -N(H)S(=O)2H), alkyl, alkenyl, alkynyl, cyclohydrocarbyl (e.g., cycloalkyl, cycloalkenyl, or cycloalkynyl), heterocyclohydrocarbyl (e.g., one selected from S, N, and O), heterocycloalkyl containing one or more heteroatoms, or heterocycloalkenyl containing one or more heteroatoms selected from S, N, and O), aryl (e.g., phenyl or a fused ring group), heteroaryl (e.g., an 8- to 10-membered bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur), -C(=O)SRiii, -C(=N-CN)N(Riii), -C(=NO-CH3)N(Riii), -C(=N-SO2-NH2)N(Riii), -C(=CH-NO2)N(R iii)2, -OC(=O)N(Riii)2, -CHN(Riii)N(Riii)2, -C(=O)N(Riii)ORiii, -N(Riii)2C(=O)ORiii, -OP(=O)(ORiii)2, -P(=O)(ORiii)2, -N(ORiii)C (=O)Riii, -N(ORiii)S(=O)2Riii, -N(ORiii)C(=O)ORiii, -N(ORiii)C(=O)N(Riii)2, -N(ORiii)C(=S)N(Riii)2, -N(ORiii)C(NRiii)N(Riii)2,In any of the above, R is hydrogen, or alkyl, or alkenyl, or alkynyl, or heteroalkyl, or heteroalkenyl, or heteroalkynyl, as defined herein. In some embodiments, R is hydrogen, or C-C, as defined herein. 12 Alkyl, or C2-C 12 Alkenyl, or C2-C 12 Alkynyl, or C2-C 12 Heteroalkyl, or C3-C 12 Heteroalkenyl, or C3-C 12 It is heteroalkynyl.

[0025] In certain embodiments, the substituents themselves may be further substituted, for example, with one or more substituents as defined herein. For example, C1-C6 alkyl as a substituent may be further substituted with one or more substituents as defined herein. As used herein, the term "halo" or "halogen" group is defined to include F, Cl, Br, or I.

[0026] As used herein, "pharmaceutically acceptable salts" refers to acid or base salts of compounds of the present disclosure that retain the biological effectiveness and properties of the compounds of the present disclosure and that are not typically biologically or otherwise undesirable. In many cases, the compounds of the present invention are capable of forming acid and / or base salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto.

[0027] The compounds of the present disclosure can form pharmaceutically acceptable acid addition salts with inorganic and / or organic acids. Inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids include, but are not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphanic acid, camphor-10-sulfonic acid, caprylic acid, hexanoic acid, octanoic 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, glucuronic acid, glutamic acid, These include, but are not limited to, glutaric acid, 2-oxoglutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, and undecylenic acid.

[0028] Pharmaceutically acceptable base addition salts can be prepared from the compounds of the present disclosure and inorganic and / or organic bases. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, iron salts, zinc salts, copper salts, manganese salts, and aluminum salts. Preferred inorganic salts are ammonium salts, sodium salts, potassium salts, calcium salts, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary amines, secondary amines, tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, and the following basic ion exchange resins: ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, deanol, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benezamine, benzathine, ethylenediamine, glucosamine, methylglucosamine, theobromine, triethanolamine, tromethamine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0029] Numerical ranges described herein should be understood to encompass the boundaries and all subranges contained therein. For example, a range of "1 to 10" should be understood to include not only the explicitly stated values ​​1 and 10, but also individual values ​​(e.g., 2, 3, 4, 5, 6, 7, 8, and 9) and subranges (e.g., 1 to 2, 1.5 to 2.5, 1 to 3, 1.5 to 3.5, 2.5 to 4, 3 to 4.5, etc.) within the range of 1 to 10. This principle also applies to ranges using only one value as the minimum or maximum value.

[0030] As used herein, the term "isomer" refers to different compounds with the same molecular formula. "Stereoisomers" are isomers that differ only in the arrangement of 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 ratio may be called a "racemic" mixture. "Diastereoisomers" are stereoisomers that have at least two asymmetric atoms and are not mirror images of each other. "Tautomers" are isomers of a compound that are in equilibrium with each other. The concentration of isomers depends on the environment in which the compound is present, for example, whether the compound is a solid, in an organic solution, or in an aqueous solution.

[0031] In certain embodiments, "stereoisomer" also includes E isomers, Z isomers, or mixtures thereof, cis isomers, trans isomers, or mixtures thereof.

[0032] Nucleic acids and / or polynucleotides useful in the present disclosure include a coding region encoding a polypeptide of interest, a 5'-UTR at the 5'-end of the coding region, and a 3'-UTR at the 3'-end of the coding region. In some embodiments, the nucleic acid or polynucleotide further includes at least one of a polyadenylation region and a Kozak sequence. In some embodiments, the nucleic acid or polynucleotide (e.g., mRNA) may include a 5' cap structure. Any region of the nucleic acid may include one or more alternative nucleosides, such as 5-substituted uridine (e.g., 5-methoxyuridine), 1-substituted pseudouridine (e.g., 1-methyl-pseudouridine or 1-ethyl-pseudouridine), and / or 5-substituted cytidine (e.g., 5-methyl-cytidine).

[0033] The term "5'-UTR" or "5'-untranslated region" refers to an RNA sequence in an mRNA that is located upstream of a coding sequence and is not translated into protein. The 5'-UTR of a gene typically begins at the transcription initiation site and ends at the nucleotide upstream of the translation initiation codon of the coding sequence. The 5'-UTR may contain elements that control gene expression, such as a ribosome binding site, a 5'-terminal oligopyrimidine tract, and a translation initiation signal such as a Kozak sequence. mRNA may be posttranscriptionally modified by the addition of a 5'-cap. Therefore, the 5'-UTR in a mature mRNA can also refer to the RNA sequence between the 5'-cap and the initiation codon. As used herein, the term "3'-untranslated region" or "3'-UTR" refers to an RNA sequence in an mRNA that is located downstream of a coding sequence and is not translated into protein. The 3'-UTR in an mRNA is located between the stop codon of the coding sequence and the poly(A) sequence, for example, beginning at the nucleotide downstream of the stop codon and ending at the nucleotide upstream of the poly(A) sequence. The sequences of the 5'-UTR and / or 3'-UTR may be homologous or heterologous to the coding region sequence. The 3'-UTR may consist of a 3'-UTR derived from at least one of the albumin gene, the α-globin gene, the β-globin gene, the tyrosine hydroxylase gene, the lipoxygenase gene, and the collagen α gene.

[0034] As used herein, the terms "polyadenylation region," "poly(A) sequence," and "poly(A)" are used interchangeably. Naturally occurring poly(A) sequences typically consist of adenine ribonucleotides. Preferably, "polyadenylation region" refers to a poly(A) sequence containing nucleotides or nucleotide segments other than adenine ribonucleotides. Poly(A) sequences are usually located at the 3' end of an mRNA, e.g., at the 3' end (downstream) of the 3'-UTR. The length of the poly(A) region may vary. In particular, in some embodiments, the length of the poly(A) region of a nucleic acid molecule of the present disclosure is at least 30 nucleotides; in some embodiments, the length of the poly(A) region of a nucleic acid molecule of the present disclosure is at least 80 nucleotides; and in some embodiments, the length of the poly(A) region of a nucleic acid molecule of the present disclosure is at least 100 nucleotides.

[0035] As used herein, the term "5' cap structure" refers to a 5' cap structure typically located at the 5' end of a mature mRNA. In some embodiments, the 5' cap structure is linked to the 5' end of an mRNA via a 5'-5'-triphosphate bond. The 5' cap structure is typically formed from modified (e.g., methylated) ribonucleotides (particularly guanine nucleotide derivatives). For example, m7GpppN (cap 0, or "cap 0" is a cap structure formed by the interaction of the 5'-phosphate group of hnRNA with the 5'-phosphate group of m7GTP under the action of guanylate transferase to form a 5',5'-phosphodiester bond), where N is the terminal 5' nucleotide of the nucleic acid having the 5'-cap structure. In some embodiments, 5' cap structures include, but are not limited to, cap 0, cap 1 (a cap structure formed by further methylating the 2'-OH of the ribose on the first nucleotide of an hnRNA based on cap 0, or "cap 1"), cap 2 (a cap structure formed by further methylating the 2'-OH of the ribose on the second nucleotide of an hnRNA based on cap 1, or "cap 2"), cap 4, a cap 0 analog, a cap 1 analog, a cap 2 analog, or a cap 4 analog.

[0036] Amino lipid compounds In one aspect, the present disclosure provides an amino lipid compound represented by the following formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: [ka] During the ceremony, A1, A2, and A3 are one of the following:

[0037] (1) In the absence of a dashed line connecting A1 and A2 and a dashed line connecting A1 and A3, A1 is a C1-C5 hydrocarbyl or a C1-C5 heterohydrocarbyl, A2 is a C1-C5 hydrocarbyl or a C1-C5 heterohydrocarbyl, and A3 is a C1-C5 hydrocarbylene or a bond; (2) if the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, then A1 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A2 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2 together with the nitrogen atom to which they are both attached form a 4-, 5-, or 6-membered ring; or (3) if the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, then A1 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A2 is C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both attached, form a 4-, 5-, or 6-membered ring; A4 is a C1-C5 hydrocarbylene or a bond; A5 is C1-C 16 is a hydrocarbylene or bond; A6 is C1-C 16 is a hydrocarbylene or bond; A7 is C1-C 18 is a hydrocarbylene or bond; A8 is C1-C 18 is a hydrocarbylene or bond; Z1 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)NR3-, or -NR3C(=O)-; R3 is H or C1-C8 hydrocarbylene; Z2 is -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)NR4-, or -NR4C(=O)-; R4 is H or C1-C3 hydrocarbylene; Y is -Z3C(=O)Z4- or -N(R5)-; Z3 is -O-, -N(R6)-, -S-, or a bond; Z4 is -O-, -N(R7)-, -S-, or a bond; R5 is -C(=O)A9Z5A 10 or -C(=O)A 11 and; Z5 is -O- or -S-; A9 is a C1-C3 hydrocarbylene or a bond; A 10 is C1-C8 hydrocarbyl; A 11 is a C1-C3 hydrocarbyl; R6 is H, or C1-C8 hydrocarbyl; R7 is H, or C1-C8 hydrocarbyl; X is C or N; R1 is H or C1-C 18 hydrocarbyl, Z6R8, or -CH(OR9)2; Z6 is -C(=O)O-, -OC(=O)-, or -O-; R8 is H, C1-C 18 Hydrocarbyl or C1-C containing O or S 18 is heterohydrocarbyl; R9 is C1-C 18 Hydrocarbyl or C1-C containing O or S 18 is heterohydrocarbyl; R2 is H or C1-C 18 Hydrocarbyl, Z7R 10 , or -CH(OR 11 )2; Z7 is -C(=O)O-, -OC(=O)-, or -O-; R10 is H, C1-C 18 Hydrocarbyl or C1-C containing O or S 18 is heterohydrocarbyl; R 11 is C1-C 18 Hydrocarbyl or C1-C containing O or S 18 is heterohydrocarbyl; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is alkylene, alkenylene, or alkynylene; Preferably, the heterohydrocarbyl is a heteroalkyl, heteroalkenyl, or heteroalkynyl.

[0038] In some embodiments, the present disclosure provides a compound wherein R1 is Z6R8 or -CH(OR9)2 and R2 is Z7R 10 or -CH(OR 11 )2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0039] In some embodiments, in the amino lipid compounds represented by Formula (I), when there is no dashed line connecting A1 to A2 and no dashed line connecting A1 to A3, A1 is a C1-C5 hydrocarbyl or a C1-C5 heterohydrocarbyl, A2 is a C1-C5 hydrocarbyl or a C1-C5 heterohydrocarbyl, and A3 is a C1-C5 hydrocarbylene or a bond, i.e., having the structure represented by Formula (Ia): [ka] wherein A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1, and R2 are as defined in formula (I).

[0040] In some embodiments, in the amino lipid compound of Formula (I), if the dashed line connecting A1 and A2 is a bond, and there is no dashed line connecting A1 and A3, then A1 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A2 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both attached, form a 4-, 5-, or 6-membered ring, i.e., having a structure represented by Formula (Ib): [ka] wherein A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1, and R2 are as defined in formula (I).

[0041] In some embodiments, in the amino lipid compound of Formula (I), when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A1 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A2 is C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both attached, form a 4-, 5-, or 6-membered ring, i.e., having a structure represented by Formula (Ic): [ka] wherein A4, A5, A6, A7, A8, Z1, Z2, Y, X, R1, and R2 are as defined in formula (I).

[0042] In some embodiments, the amino lipid compound of formula (I), when X is C, has the structure of formula (Id): [ka] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R1, and R2 are as defined in formula (I).

[0043] In some embodiments, the amino lipid compound of formula (I), when X is N, has a structure of formula (Ie): [ka] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R1, and R2 are as defined in formula (I).

[0044] In some embodiments, the amino lipid compound of formula (I) has a structure of formula (II) when R1 is -CH(OR9)2: [ka] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, X, R2, and R9 are as defined in formula (I).

[0045] In some embodiments, the amino lipid compound of formula (II), when X is C, has the structure of formula (IIa): [ka] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R2, and R9 are as defined in formula (I).

[0046] In some embodiments, the amino lipid compound of formula (II), when X is N, has the structure of formula (IIb): [ka] wherein A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R2, and R9 are as defined in formula (I).

[0047] In some embodiments, the amino lipid compounds of formula (I) are those in which R1 is -CH(OR9)2 and R2 is -CH(OR 11 )2, it has a structure represented by formula (III): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, X, R9, and R 11 is as defined in formula (I).

[0048] In some embodiments, the amino lipid compound of formula (III), when X is C, has the structure of formula (IIIa): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R9, and R 11 is as defined in formula (I).

[0049] In some embodiments, the amino lipid compound of formula (III), when X is N, has the structure of formula (IIIb): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y, R9, and R 11 is as defined in formula (I).

[0050] In some embodiments, the amino lipid compound of formula (I) is Y is -Z3C(=O)Z4-; Z3 is -O-; Z4 is -O-; X is C; R1 is -CH(OR9)2 and R2 is -CH(OR 11 )2, Having a structure represented by formula (IV): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9, and R 11 is as defined in formula (I).

[0051] In some embodiments, the amino lipid compound of formula (I) is Y is -Z3C(=O)Z4-; Z3 is -O-; Z4 is -O-; X is C; Z1 is -C(=O)O-, or -OC(=O)-; Z2 is -C(=O)O-, or -OC(=O)-; R1 is -CH(OR9)2 and R2 is -CH(OR 11 )2, Having a structure represented by formula (Va), (Vb), (Vc), or (Vd): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, R9, and R 11 is as defined in formula (I).

[0052] In some embodiments, the present disclosure provides an amino lipid compound represented by Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 is C1, C2, C3, C4, or C5 hydrocarbyl, C1, C2, C3, C4, or C5 heterohydrocarbyl, C1, C2, or C3 hydrocarbylene, or C1, C2, or C3 heterohydrocarbylene.

[0053] In some embodiments, the present disclosure provides an amino lipid compound represented by Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A2 is C1, C2, C3, C4, or C5 hydrocarbyl, C1, C2, C3, C4, or C5 heterohydrocarbyl, C1, C2, or C3 hydrocarbylene, or C1, C2, or C3 heterohydrocarbylene.

[0054] In some embodiments, the present disclosure provides an amino lipid compound represented by Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is a C1, C2, C3, C4, or C5 hydrocarbylene or a bond.

[0055] In some embodiments, the present disclosure provides an amino lipid compound represented by Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A4 is a C1, C2, or C3 hydrocarbylene or a bond.

[0056] In some embodiments, the present disclosure provides a method for treating A5 comprising administering to a patient a method for treating a patient, the method comprising administering to a patient a method for treating a patient, the method comprising administering to a patient a method for treating a patient, the method comprising administering to a patient a method for treating a patient 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16Provided is an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a hydrocarbylene.

[0057] In some embodiments, the present disclosure provides a method for treating A6 comprising administering to a patient a method for treating A6 comprising administering to a patient a method for treating A6 comprising administering to a patient a method for treating A6 comprising administering to a patient a method for treating A6 10 , C 11 , C 12 , C 13 , C 14 , C 15 , or C 16 Provided is an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a hydrocarbylene.

[0058] In some embodiments, the present disclosure provides a method for treating A7 comprising administering to a patient a compound selected from the group consisting of C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0059] In some embodiments, the present disclosure provides a method for treating A8 comprising administering to a patient a method for treating A8 comprising administering to a patient a method for treating A8 comprising administering to a patient a method for treating A8 comprising administering to a patient a method for treating A8 10 , C 11, C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0060] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A9 is C1, C2, or C3 hydrocarbylene.

[0061] In some embodiments, the present disclosure provides a 10 is C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0062] In some embodiments, the present disclosure provides a 11 is C1, C2, or C3 hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0063] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R6 is H, or C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbyl.

[0064] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), or (IIIb) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R7 is H, or C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbyl.

[0065] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), or (IV) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R3 is H, or C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbylene.

[0066] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), or (IV) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R4 is H, or C1, C2, or C3 hydrocarbylene.

[0067] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), or (IV) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R4 is an optionally substituted C1-C3 hydrocarbylene; preferably, R4 is a C1-C3 hydrocarbylene optionally substituted with hydroxyl, an ester group, hydrocarbyloxy, hydrocarbyl, halogen, oxygen, sulfur, amino, or amido group.

[0068] In some embodiments, the present disclosure provides a method for treating a cycloaliphatic disorder in which R is H or C, ... 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a hydrocarbyl.

[0069] In some embodiments, the present disclosure provides a compound in which R is H, a linear C-C 18 Alkyl, straight chain C2-C 18 Alkenyl, or straight chain C2-C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is alkynyl.

[0070] In some embodiments, the present disclosure provides a linear C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C16 , C 17 , or C 18 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is alkynyl.

[0071] In some embodiments, the present disclosure provides a method for treating a rhodium salt of ... 18 Alkyl, branched C3-C 18 Alkenyl, or branched C4-C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is alkynyl.

[0072] In some embodiments, the present disclosure provides that R is a branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12, C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is alkynyl.

[0073] In some embodiments, the present disclosure provides a method for treating a cancer comprising administering to a patient a cancer-related disorder, wherein R is C, ... 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Hydrocarbyl or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), which is a heterohydrocarbyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0074] In some embodiments, the present disclosure provides a method for treating a medicament comprising administering to a subject therapies ... 18 Alkyl, or straight chain C2-C 18 Alkenyl, or straight chain C2-C 18Alkynyl or straight chain C1-C containing O or S 18 Heteroalkyl or straight chain C2-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), which is a heteroalkenyl or a linear heteroalkynyl containing O or S, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0075] In some embodiments, the present disclosure provides that R8 is a linear C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0076] In some embodiments, the present disclosure provides a method for treating a rhodium salt of a rhodium salt of a branched C3-C 18 Alkyl or branched C3-C 18 Alkenyl, or branched C4-C 18 Alkynyl or branched C3-C containing O or S 18 Heteroalkyl or branched C3-C containing O or S 18 Heteroalkenyl or branched C4-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0077] In some embodiments, the present disclosure provides that R is a branched C, C, C, C, C, C, C, C, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0078] In some embodiments, the present disclosure provides [ka] The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), or (Ie), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0079] In some embodiments, the present disclosure provides a method for treating a cancer comprising administering to a patient a cancer-related disorder, wherein R is C, ... 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Hydrocarbyl or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is a heterohydrocarbyl amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0080] In some embodiments, the present disclosure provides a method for treating a rhodium salt of ... 18 Alkyl, or straight chain C2-C 18 Alkenyl, or straight chain C2-C 18 Alkynyl or straight chain C1-C containing O or S 18 Heteroalkyl or straight chain C2-C containing O or S 18 Heteroalkenyl or straight chain C2-C containing O or S18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0081] In some embodiments, the present disclosure provides that R9 is a linear C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0082] In some embodiments, the present disclosure provides a method for treating a rhodium salt of a rhodium salt of a branched C3-C 18 Alkyl or branched C3-C 18 Alkenyl, or branched C4-C 18 Alkynyl or branched C3-C containing O or S 18 Heteroalkyl or branched C3-C containing O or S 18 Heteroalkenyl or branched C4-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0083] In some embodiments, the present disclosure provides that R9 is a branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C14 , C 15 , C 16 , C 17 , or C 18 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0084] In some embodiments, the present disclosure provides [ka] The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), wherein:

[0085] In some embodiments, the present disclosure provides a method for treating a cycloaliphatic disorder in which R2 is H or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a hydrocarbyl.

[0086] In some embodiments, the present disclosure provides a compound wherein R2 is H, a linear C1-C 18 Alkyl, straight chain C2-C 18 Alkenyl, or straight chain C2-C 18The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is an alkynyl.

[0087] In some embodiments, the present disclosure provides that R2 is a linear C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is an alkynyl.

[0088] In some embodiments, the present disclosure provides a method for treating a cyclohexyl 1-hydroxybenzoate comprising administering to a subject a cyclohexyl 1-hydroxybenzoate, wherein R is H, a branched C 18 Alkyl, branched C3-C 18 Alkenyl, or branched C4-C 18The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is an alkynyl.

[0089] In some embodiments, the present disclosure provides that R2 is a branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is an alkynyl.

[0090] In some embodiments, the present disclosure provides R 10 C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17, or C 18 Hydrocarbyl, or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl.

[0091] In some embodiments, the present disclosure provides R 10 is a straight chain C1-C 18 Alkyl, or straight chain C2-C 18 Alkenyl, or straight chain C2-C 18 Alkynyl or straight chain C1-C containing O or S 18 Heteroalkyl or straight chain C2-C containing O or S 18 Heteroalkenyl or straight chain C2-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heteroalkynyl. In some embodiments, the present disclosure provides R 10 Straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14, C 15 , C 16 , C 17 , or C 18 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heteroalkynyl.

[0092] In some embodiments, the present disclosure provides R 10 Branch C3-C 18Alkyl or branched C3-C 18 Alkenyl, or branched C4-C 18 Alkynyl or branched C3-C containing O or S 18 Heteroalkyl or branched C3-C containing O or S 18 Heteroalkenyl or branched C4-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heteroalkynyl.

[0093] In some embodiments, the present disclosure provides R 10 Branches C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C17 , or C 18 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heteroalkynyl.

[0094] In some embodiments, the present disclosure provides R 10 but [ka] The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0095] In some embodiments, the present disclosure provides R 11 are C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18Hydrocarbyl or C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is a heterohydrocarbyl amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0096] In some embodiments, the present disclosure provides R 11 is a straight chain C1-C 18 Alkyl, or straight chain C2-C 18 Alkenyl, or straight chain C2-C 18 Alkynyl or straight chain C1-C containing O or S 18 Heteroalkyl or straight chain C2-C containing O or S 18 Heteroalkenyl or straight chain C2-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0097] In some embodiments, the present disclosure provides R 11 Straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0098] In some embodiments, the present disclosure provides R 11 Branch C3-C 18 Alkyl or branched C3-C 18 Alkenyl, or branched C4-C 18 Alkynyl or branched C3-C containing O or S 18 Heteroalkyl or branched C3-C containing O or S 18 Heteroalkenyl or branched C4-C containing O or S 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0099] In some embodiments, the present disclosure provides R 11 Branches C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 Provided is an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), which is a heteroalkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0100] In some embodiments, the present disclosure provides R 11 but [ka] The present invention provides an amino lipid compound represented by the above formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), wherein:

[0101] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (Va), (Vb), (Vc), or (Vd), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the hydrocarbyl, hydrocarbylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, and heterohydrocarbyl are optionally substituted; and the hydrocarbyl, hydrocarbylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, and heterohydrocarbyl are optionally substituted with hydroxyl, ester group, hydrocarbyloxy, hydrocarbyl, halogen, oxygen, sulfur, amino, or amido group.

[0102] In yet another aspect, the present disclosure provides an amino lipid compound represented by the following (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: [ka] During the ceremony A1, A2, and A3 are one of the following: (1) In the absence of a dashed line connecting A1 and A2 and a dashed line connecting A1 and A3, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond; (2) If the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (3) If the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene, and A1, A2, and A3, together with the nitrogen atom to which they are all bonded, form a nitrogen-containing spiro heterocycle, a nitrogen-containing fused heterocycle, or a nitrogen-containing bridged heterocycle; A4 is a C1-C5 hydrocarbylene or a bond; A5, A6, A7, A8, and A 12 are independently C1-C 18 is a hydrocarbylene or bond; Z1 and Z2 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10)-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-, Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2 NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP(=O )O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S-, or -SC(=O)O-; X is C or N; R1 is H, C1-C 24 Hydrocarbyl, C1-C 24 heterohydrocarbyl, Z6R8, or -CH(OR9)2; R2 is H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, Z7R 10 , or -CH(OR 11 )2; Z3 and Z4 are each independently -O-, -N(R6)-, -S-, or a bond; Z6 and Z7 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; R5 is -C(=O)A9Z5A 10 , -C(=O)A 11 , H, or C1-C8 hydrocarbyl; Z5 is -O- or -S-; each R6 is independently H or C1-C8 hydrocarbyl; R8 and R 10 are independently H, C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; R9 and R 11 are independently C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; A9 is a C1-C8 hydrocarbylene or a bond; A 10 and A 11 are each independently C1-C8 hydrocarbyl; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is alkylene, alkenylene, or alkynylene; Preferably, the hydrocarbylene is alkylene, alkenylene, or heteroalkynylene; Preferably, the heterohydrocarbyl is heteroalkyl, heteroalkenyl, or heteroalkynyl; Preferably, the heterohydrocarbylene is a heteroalkylene, heteroalkenylene, or heteroalkynylene.

[0103] In yet another aspect, the present disclosure provides an amino lipid compound represented by the following formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: [ka] During the ceremony, A1, A2, and A3 are one of the following: (1) In the absence of a dashed line connecting A1 and A2 and a dashed line connecting A1 and A3, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond; (2) If the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (3) If the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is H, C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene, and A1, A2, and A3, together with the nitrogen atom to which they are all bonded, form a nitrogen-containing spiro heterocycle, a nitrogen-containing fused heterocycle, or a nitrogen-containing bridged heterocycle; A4 is a C1-C5 hydrocarbylene or a bond; A5, A6, A7, A8, and A 12 are independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; Z1 and Z2 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O) 2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP(= O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S-, or -SC(=O)O-; X is C or N; R1 is H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, Z6R8, -C(R6)(OA 13 Z8R9)2, -C(R6)(SA 13Z8R9)2, or -C(R6)(SA 13 Z8R9)(OA 13 Z8R9); R2 is H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, Z7R 10 , -C(R6)(OA 14 Z9R 11 )2, -C(R6)(SA 14 Z9R 11 )2, or -C(R6)(SA 14 Z9R 11 )(OA 14 Z9R 11 ) and; Z3 and Z4 are each independently -O-, -N(R6)-, -S-, or a bond; Z6 and Z7 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; R5 is -C(=O)A9Z5A 10 , -C(=O)A 11 , H, or C1-C8 hydrocarbyl; Z5 is -O- or -S-; Z8 and Z9 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(=O)2O-, or a bond; each R6 is independently H or C1-C8 hydrocarbyl; R8 and R 10 are independently H, C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; R9 and R 11 are independently C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; A9 is a C1-C8 hydrocarbylene or a bond; A 10 and A 11 are each independently C1-C8 hydrocarbyl; A 13 and A 14 are each independently C1-C8 hydrocarbylene, C1-C8 heterohydrocarbylene, or a bond; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is alkylene, alkenylene, or alkynylene; Preferably, the heterohydrocarbyl is heteroalkyl, heteroalkenyl, or heteroalkynyl; Preferably, the heterohydrocarbylene is a heteroalkylene, heteroalkenylene, or heteroalkynylene.

[0104] The present disclosure provides an amino lipid compound represented by formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, comprising one or more of the following characteristics, where applicable:

[0105] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 is H and A2 is H, or A1 is H and A2 is not H, or A1 is not H and A2 is H.

[0106] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2 are each independently C1, C2, C3, C4, or C5 hydrocarbyl, or C1, C2, C3, C4, or C5 heterohydrocarbyl, or C1, C2, C3, C4, or C5 hydrocarbylene, or C1, C2, C3, C4, or C5 heterohydrocarbylene.

[0107] In some embodiments, the present disclosure provides that A1 and A2 are each independently C1-C5 alkyl, or C2-C5 alkenyl having one or two double bonds, or C2-C5 alkynyl having one or two triple bonds, or C1-C5 heteroalkyl containing S or O, or C2-C5 heteroalkenyl having one or two double bonds and containing S or O, or C2-C5 heteroalkynyl having one or two triple bonds and containing S or O, or C1-C5 alkylene or a C2-C5 alkenylene having one or two double bonds, or a C2-C5 alkynylene having one or two triple bonds, or a C1-C5 heteroalkylene containing S or O, or a C2-C5 heteroalkenylene having one or two double bonds and containing S or O, or a C2-C5 heteroalkynylene having one or two triple bonds and containing S or O, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0108] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and / or A2 is unsubstituted C1-C5 hydrocarbyl, or unsubstituted C1-C5 heterohydrocarbyl, or unsubstituted C1-C5 hydrocarbylene, or unsubstituted C1-C5 heterohydrocarbylene.

[0109] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and / or A2 is a substituted C1-C5 hydrocarbyl, or a substituted C1-C5 heterohydrocarbyl, or a substituted C1-C5 hydrocarbylene, or a substituted C1-C5 heterohydrocarbylene.

[0110] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and / or A2 is substituted C1-C5 alkyl, or substituted C2-C5 alkenyl, or substituted C3-C5 alkynyl, or substituted C1-C5 alkylene, or substituted C2-C5 alkenylene, or substituted C3-C5 alkynylene.

[0111] In some embodiments, the present disclosure provides that A1 and / or A2 are C1-C5 alkyl, C2-C5 alkenyl, C3-C5 alkynyl, C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene, and are selected from the group consisting of hydroxyl, cyano, phenyl, C3-C7 cyclohydrocarbyl, C3-C7 cyclohydrocarbyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-10 membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -OR 12 , -C(=O)R 12 , -C(=O)SR 12 , -OC(=O)R 12 , -OC(=O)OR 12 , -N(R 12 )2, -C(=O)N(R 12 )2, -C(=S)N(R 12 )2, -S(=O)2R 12 , -S(=O)2N(R 12 )2, -OC(=O)N(R 12 )2, -CH(NR 12 )N(R 12 )2, -C(NR 12 )2R 12 , -C(=O)N(R 12 ) OR 12 , -CH(R 12 )N(R 12 )2C(=O)OR 12 , -C(R 12 )3, -N(R 12 )C(=O)R 12 , -N(R12 )C(=O)OR 12 , -N(R 12 )S(=O)2R 12 , -N(R 12 )C(=O)N(R 12 )2, -N(R 12 )C(=S)N(R 12 )2, -N(R 12 )C(NR 12 )N(R 12 )2, -N(R 12 )C(CHR 12 )N(R 12 )2, -N(OR 12 )C(=O)R 12 , -N(OR 12 )S(=O)2R 12 , -N(OR 12 )C(=O)OR 12 , -N(OR 12 )C(=O)N(R 12 )2, -N(OR 12 )C(=S)N(R 12 )2, -N(OR 12 )C(NR 12 )N(R 12 )2, -N(OR 12 )C(CHR 12 )N(R 12 )2, -OP(=O)(OR 12 )2, -P(=O)(OR 12 )2, or 3- to 7-membered cycloaliphatic rings and 3- to 7-membered heterocycloyl rings each containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2, -C(=NO-CH3)N(R 12 )2, -C(=N-SO2-NH2)N(R 12 )2, -C(=CH-NO2)N(R 12 )2, or -C(=O)OR 12 wherein each R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is a heteroalkynyl.

[0112] In some embodiments, the present disclosure provides compounds wherein A and / or A contain 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and are selected from C-C alkyl, ═O, —C-C alkylene-hydroxyl, —C(═O)N(R 15 ) C3-C7 cyclohydrocarbyl substituted with 2; 8-10 membered bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur and optionally substituted with C1-C5 alkyl, hydroxyl; [ka] C1-C5 alkyl, C2-C5 alkenyl, C3-C5 alkynyl, C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene, each substituted with 15 are independently H or C1-C3 alkyl, and d is 0, 1, 2, 3, 4, or 5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0113] In some embodiments, the present disclosure provides that A1 and / or A2 [ka] The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0114] In some embodiments, the present disclosure provides that A1 and / or A2 [ka] may be The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein a is 1, 2, 3, 4, or 5; preferably, a is 1, 2, or 3.

[0115] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is a bond. In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1, C2, C3, C4, or C5 hydrocarbylene. In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds.

[0116] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is unsubstituted C1-C5 alkylene, or unsubstituted C2-C5 alkenylene, or unsubstituted C3-C5 alkynylene. In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is substituted C1-C5 alkylene, or substituted C2-C5 alkenylene, or substituted C3-C5 alkynylene.

[0117] In some embodiments, the present disclosure provides: A3 is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene, substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0118] In some embodiments, the present disclosure provides 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 When R is C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene substituted with 13 and / or R 14 may be bonded to the C atom of A3 to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0119] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein, when the dashed line connecting A1 and A2 is a bond and when there is no dashed line connecting A1 and A3, A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycle.

[0120] In some embodiments, A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 3-, 4-, 5-, or 6-membered heterocycle. In some embodiments, A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 4-, 5-, or 6-membered heterocycle.

[0121] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein, when the dashed line connecting A1 and A3 is a bond and when there is no dashed line connecting A1 and A2, A1 and A3 together with the nitrogen atom to which they are both attached form an N-containing 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycle.

[0122] In some embodiments, A1 and A3 together with the nitrogen atom to which they are both attached form an N-containing 3-, 4-, 5-, or 6-membered heterocycle. In some embodiments, A1 and A3 together with the nitrogen atom to which they are both attached form an N-containing 4-, 5-, or 6-membered heterocycle.

[0123] In some embodiments, the present disclosure provides: [ka] but [ka] [ka] (wherein c is 1, 2, 3, 4, or 5; preferably, c is 2, 3, or 4; preferably, c is 2 or 3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0124] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A4 is a bond.

[0125] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A4 is C1, C2, C3, C4, or C5 hydrocarbylene.

[0126] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A4 is C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds.

[0127] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A4 is unsubstituted C1-C5 alkylene, or unsubstituted C2-C5 alkenylene, or unsubstituted C3-C5 alkynylene.

[0128] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A4 is substituted C1-C5 alkylene, or substituted C2-C5 alkenylene, or substituted C3-C5 alkynylene.

[0129] In some embodiments, the present disclosure provides that A4 is selected from the group consisting of hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, —R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 , C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene, substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0130] In some embodiments, the present disclosure provides a compound wherein A4 is -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 When R is C1-C5 alkylene, C2-C5 alkenylene, or C3-C5 alkynylene substituted with 13 and / or R 14 may be bonded to the C atom of A4 to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring, an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0131] In some embodiments, the present disclosure provides A5, A6, A7, A8, and A 12 are independent of each other, C1-C 18 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is a hydrocarbylene or bond.

[0132] In some embodiments, the present disclosure provides A5, A6, A7, A8, and A 12 are independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17, or C 18 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is a hydrocarbylene or bond.

[0133] In some embodiments, A5, A6, A7, A8, and A 12 are each independently a bond. In some other embodiments, A5, A6, A7, A8, and A 12 are independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is a hydrocarbylene.

[0134] In some embodiments, the present disclosure provides A5, A6, A7, A8, and A 12 are independent of each other, C1-C 18 Alkylene or C2-C with 1, 2, 3 or more double bonds 18 Alkenylene or C2-C with 1, 2, 3, or more triple bonds 18 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is an alkynylene.

[0135] In some embodiments, the present disclosure provides a 12 are C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18The present invention provides an amino lipid compound represented by the above formula (II-I), which is a hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0136] In some embodiments, the present disclosure provides a 12 is a bond, and A5 and A6 are not both C1 hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0137] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A7 and A8 are each independently C1, C2, C3, C4, C5, C6, or C7 hydrocarbylene or a bond.

[0138] In some embodiments, the present disclosure provides a 12 is C1 hydrocarbylene, and A5 is C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 or A 12 is C1 hydrocarbylene, and A6 is C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 The present invention provides an amino lipid compound represented by the above formula (II-I), which is a hydrocarbylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0139] In some embodiments, the present disclosure provides that A5 and / or A6 are unsubstituted C1-C12 Alkylene or unsubstituted C2-C 12 Alkenylene or unsubstituted C3-C 12 The amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, is provided, wherein A5 and / or A6 are unsubstituted C1-C 12 It is alkylene, or unsubstituted C3-C9 alkylene, or unsubstituted C4-C9 alkylene, or unsubstituted C5-C8 alkylene, or unsubstituted C8 alkylene.

[0140] In some embodiments, the present disclosure provides that A5 and / or A6 are substituted C1-C 12 Alkylene, or substituted C2-C 12 Alkenylene or substituted C3-C 12 The amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, is provided, wherein A5 and / or A6 are substituted C1-C 12 It is alkylene, or substituted C3-C9 alkylene, or substituted C4-C9 alkylene, or substituted C5-C8 alkylene, or substituted C8 alkylene.

[0141] In some embodiments, the present disclosure provides that A7 and / or A8 are unsubstituted C1-C 12 Alkylene or unsubstituted C2-C 12 Alkenylene or unsubstituted C3-C 12 The amino lipid compound represented by the above formula (II-I) or its pharmaceutically acceptable salt, or its stereoisomer is provided, wherein A7 and / or A8 are alkynylene. For example, A7 and / or A8 are unsubstituted C1-C5 alkylene, unsubstituted C2-C4 alkylene, or unsubstituted C3 alkylene.

[0142] In some embodiments, the present disclosure provides that A7 and / or A8 are substituted C1-C 12 Alkylene, or substituted C2-C 12 Alkenylene or substituted C3-C 12The amino lipid compound represented by the above formula (II-I) or its pharmaceutically acceptable salt, or its stereoisomer is provided, wherein A7 and / or A8 are alkynylene. For example, A7 and / or A8 are substituted C1-C5 alkylene, or substituted C2-C4 alkylene, or substituted C3 alkylene.

[0143] In some embodiments, the present disclosure provides a 12 Unsubstituted C1-C 12 Alkylene or unsubstituted C2-C 12 Alkenylene or unsubstituted C3-C 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is an alkynylene. For example, A 12 is unsubstituted C1-C5 alkylene or unsubstituted C1-C3 alkylene.

[0144] In some embodiments, the present disclosure provides a 12 Substitutes C1-C 12 Alkylene, or substituted C2-C 12 Alkenylene or substituted C3-C 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is an alkynylene. For example, A 12 is a substituted C1-C5 alkylene or a substituted C1-C3 alkylene.

[0145] In some embodiments, the present disclosure provides A5, A6, A7, A8 and A 12 At least one of is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 , substituted with, C1-C 12 Alkylene, C2-C 12 Alkenylene, or C3-C 12 is alkynylene, During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0146] In some embodiments, the present disclosure provides A5, A6, A7, A8 and A 12 At least one of the following is -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 Substituted with, C1-C 12 Alkylene, C2-C 12 Alkenylene, or C3-C 12 When R is alkynylene, 13 and / or R 14 is substituted A5, A6, A7, A8, or A 12 and a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0147] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A9 is a bond.

[0148] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A9 is C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbylene, or C1, C2, C3, C4, C5, C6, C7, or C8 heterohydrocarbylene.

[0149] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A9 is C1-C8 alkylene, or C2-C8 alkenylene having one, two or more double bonds, or C2-C8 alkynylene having one, two or more triple bonds.

[0150] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each A9 is independently unsubstituted C1-C8 alkylene, or unsubstituted C2-C8 alkenylene, or unsubstituted C3-C8 alkynylene.

[0151] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein at least one of A9 is substituted C1-C8 alkylene, or substituted C2-C8 alkenylene, or substituted C3-C8 alkynylene.

[0152] In some embodiments, the present disclosure provides that at least one of the A groups is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, —R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR14 C1-C8 alkylene, C2-C8 alkenylene, or C3-C8 alkynylene, substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0153] In some embodiments, the present disclosure provides 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14)2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 When R is C1-C8 alkylene, C2-C8 alkenylene, or C3-C8 alkynylene substituted with 13 and / or R 14 may be bonded to the C atom of the substituted A to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0154] In some embodiments, the present disclosure provides a 10 and A 11 are each independently C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbyl, or C1, C2, C3, C4, C5, C6, C7, or C8 heterohydrocarbyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0155] In some embodiments, the present disclosure provides a 10 and A 11 are each independently C1-C8 alkyl, or C2-C8 alkenyl having one, two or more double bonds, or C2-C8 alkynyl having one, two or more triple bonds, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0156] In some embodiments, the present disclosure provides 10 and / or each A 11is unsubstituted C1-C8 alkyl, or unsubstituted C2-C8 alkenyl, or unsubstituted C3-C8 alkynyl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0157] In some embodiments, the present disclosure provides the method of claim 1. 10 Group and / or the above A 11 Provided is an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein at least one of the groups is substituted C1-C8 alkyl, or substituted C2-C8 alkenyl, or substituted C3-C8 alkynyl.

[0158] In some embodiments, the present disclosure provides the method of claim 1. 10 Group and / or the above A 11 At least one of the groups is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 C1-C8 alkyl, C2-C8 alkenyl, or C3-C8 alkynyl substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0159] In some embodiments, the present disclosure provides a 10 and / or A 11 Ga-R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13C(=O)OR 14 When R is C1-C8 alkyl, C2-C8 alkenyl, or C3-C8 alkynyl substituted with 13 and / or R 14 is the substituted A 10 or A 11 and a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0160] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R5 is unsubstituted C1-C8 alkyl, or unsubstituted C2-C8 alkenyl, or unsubstituted C2-C8 alkynyl. In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R5 is substituted C1-C8 alkyl, or substituted C2-C8 alkenyl, or substituted C2-C8 alkynyl.

[0161] In some embodiments, the present disclosure provides a compound wherein R5 is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, —R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0162] In some embodiments, the present disclosure provides 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 When R is C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl substituted with 13 and / or R 14 may be bonded to the C atom of R5 to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0163] In some embodiments, the present disclosure provides a method for the preparation of a cycloalkyl group comprising the steps of: Y1 being -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -C(=S)O-, -OC(=S)-, -C(=S)-, -C(=S)S-, -SC(=S)-, -C(=S)N(R6)-, -N(R6)C(=S)-, -OC(=S)O-, -OC(=S)S-, -SC(=S) O-, -SC(=S)S-, -N(R6)C(=S)O-, -OC(=S)N(R6)-, -N(R6)C(=S)N(R6)-, -SC(=S)N(R6)-, -N(R6)C(=S)S-, -N(C(=S)A9OA 10)-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S-, or -SC(=O)O-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0164] In some embodiments, Y is -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R)-, -N(R)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R)C(=O)O-, -OC(=O)N(R)-, -N(R)C(=O)N(R)-, -SC(=O)N(R)-, -N(R)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A 11 ), -OS(=O)2O-, -OS(=O)O-, -OS(=O)2NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OS(=O)2O-, -OS(=O)O-, -OP(=O)O -, -OP(=O)(OH)O-, -OP(=O)(H)O-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S-, or -SC(=O)O-.

[0165] In some embodiments, Y is —N(H)C(═O)N(H)—, —S—, —OC(═O)O—, —N(H)C(═O)O—, —OC(═O)N(H)—, —C(═O)O—, —OC(═O)—, —N((CH)C(═O)OCH 11 )C(=O)O-, -OC(=O)N((CH2)3C(=O)OC5H11 ) -, -N(H)C(=O)-, -C(=O)N(H)-, -N(C(=O)(CH2)3OC8H 17 ) -, -N(C(=O)CH2OCH3), -N(C(=O)CH3), -N(C(=O)C3H7), -N(C3H7)C(=O)O-, -OC(=O)N(C6H 13 ) -, -C(=O)N(C4H9)-, -N(CH(CH3)2)C(=O)-, -N((CH2)3C(=O)OC2H5)C(=O)O-, -N((CH2)3C(=O)OCH2CH=CHC3H7)C(=O)O-, -N(C4H9)C(=O)-, -O-, -S(=O)2O-, -OS(=O)2-, -OS(=O)2O-, -OS(=O)O-, -S(=O)2NH-, -NHS(=O)2-, -OS(=O)2NH-, -NHS(=O)2NH-, -OP(=O)(H)O-, -OP(=O)(OH)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)N(H)-, -N(H)C(=O)S-, -C(=O)S-, or -SC(=O)-.

[0166] In some embodiments, the present disclosure provides that Y1 is -C(=O)O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R) C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 ) -, -N(C(=O)A9SA<00​​​​)-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S-, or -SC(=O)O-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0167] In some embodiments, the present disclosure provides a compound wherein Z is —C(═O)O—, —O—, —C(═O)—, —S—, —C(═O)S—, —SC(═O)—, —C(═O)N(R)—, —N(R)C(═O)—, —OC(═O)O—, —OC(═O)S—, —SC(═O)O—, —SC(═O)S—, —N(R)C(═O)O—, —OC(═O)N(R)—, —N(R)C(═O)N(R)—, —SC(═O)N(R)—, —N(R)C(═O)S—, —N(C(═O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0168] In some embodiments, the present disclosure provides a method for treating a cancer of the present invention, wherein Z is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R)-, -N(R)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R)C(=O)O-, -OC(=O)N(R)-, -N(R)C(=O)N(R)-, -SC(=O)N(R)-, -N(R)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0169] In some embodiments, the present disclosure provides that R and R are each independently C, ... 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Hydrocarbyl, or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl.

[0170] In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer treatment, ... a method for treating a cancer cell, or a cancer treatment, wherein R and / or R are C-C 24 Alkyl (e.g., C5-C 16 Alkyl, C6-C 14 Alkyl, C6-C 12 alkyl), C2-C 24 Alkenyl (e.g., C5-C 16 Alkenyl, C6-C 14 Alkenyl, C6-C 12 alkenyl), C2-C 24 Alkynyl (e.g., C5-C 16 Alkynyl, C6-C 14 Alkynyl, C6-C 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0171] In some embodiments, the present disclosure provides a method for treating a rhodium salt of ... 24 Alkyl (e.g., unsubstituted C5-C 16 Alkyl, unsubstituted C6-C 14 Alkyl, unsubstituted C6-C 12 alkyl), unsubstituted C2-C 24 Alkenyl (e.g., unsubstituted C5-C 16 Alkenyl, unsubstituted C6-C 14 Alkenyl, unsubstituted C6-C 12 alkenyl), unsubstituted C2-C 24 Alkynyl (e.g., unsubstituted C5-C 16 Alkynyl, unsubstituted C6-C 14 Alkynyl, unsubstituted C6-C 12The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0172] In some embodiments, the present disclosure provides that R and / or R are substituted C-C 24 alkyl (e.g., substituted C5-C 16 Alkyl, substituted C6-C 14 Alkyl, substituted C6-C 12 alkyl), substituted C2-C 24 Alkenyl (e.g., substituted C5-C 16 Alkenyl, substituted C6-C 14 Alkenyl, substituted C6-C 12 alkenyl), substituted C2-C 24 Alkynyl (e.g., substituted C5-C 16 Alkynyl, substituted C6-C 14 Alkynyl, substituted C6-C 12 Alkynyl, substituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0173] In some embodiments, the present disclosure provides that R and R are each independently a straight chain C-C 24 Alkyl, straight chain C2-C with 1, 2, 3, 4 or more double bonds 24 Alkenyl, straight chain C2-C with 1, 2, 3, 4 or more triple bonds 24 Alkynyl, straight chain C1-C containing O or S 24 Heteroalkyl, straight chain C2-C with 1, 2, 3, 4 or more double bonds and containing O or S 24 Heteroalkenyl or straight chain C2-C with 1, 2, 3, 4 or more triple bonds and containing O or S 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0174] In some embodiments, the present disclosure provides that R and R are each independently a straight chain C, ... 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkynyl, or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0175] In some embodiments, the present disclosure provides that R and R are each independently a branched C-C 24 Alkyl or branched C3-C with 1, 2, 3, 4 or more double bonds 24 Alkenyl or branched C4-C with 1, 2, 3, 4 or more triple bonds 24 Alkynyl or branched C3-C containing O or S 24 Heteroalkyl or branched C3-C with 1, 2, 3, 4, or more double bonds and containing O or S 24Heteroalkenyl or branched C4-C with 1, 2, 3, 4, or more triple bonds and containing O or S 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0176] In some embodiments, the present disclosure provides that R and R are each independently a branched C, ... 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0177] In some embodiments, the present disclosure provides R and R 10 are independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Hydrocarbyl, or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl.

[0178] In some embodiments, the present disclosure provides R and / or R 10 But C1-C 20 Alkyl (e.g., C2-C 10 Alkyl, C2-C8 alkyl, C7-C 18 alkyl), or C1-C 16 Alkenyl (e.g., C5-C 12 alkenyl, C5-C8 alkenyl, C5 alkenyl, C6 alkenyl), or C5-C 16 Alkynyl (e.g., C5-C 12 Alkynyl, C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0179] In some embodiments, the present disclosure provides R and / or R 10 But unsubstituted C1-C 20 Alkyl (e.g., unsubstituted C-C 10 Alkyl, unsubstituted C2-C8 alkyl, unsubstituted C7-C 18 alkyl), or unsubstituted C1-C 16 Alkenyl (e.g., unsubstituted C5-C 12 alkenyl, unsubstituted C5-C8 alkenyl, unsubstituted C5 alkenyl, unsubstituted C6 alkenyl), or unsubstituted C5-C 16 Alkynyl (e.g., unsubstituted C5-C 12 Alkynyl, unsubstituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0180] In some embodiments, the present disclosure provides R and / or R 10 But substitution C1-C 20 Alkyl (e.g., substituted C-C 10 Alkyl, substituted C2-C8 alkyl, substituted C7-C 18 alkyl), or substituted C1-C 16 Alkenyl (e.g., substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C5 alkenyl, substituted C6 alkenyl), or substituted C5-C 16 Alkynyl (e.g., substituted C5-C 12 Alkynyl, substituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0181] In some embodiments, the present disclosure provides R and R 10 are each independently linear C1-C 24 Alkyl, straight chain C2-C with 1, 2, 3, 4 or more double bonds 24 Alkenyl, straight chain C2-C with 1, 2, 3, 4 or more triple bonds 24 Alkynyl, straight chain C1-C containing O or S24 Heteroalkyl, straight chain C2-C with 1, 2, 3, 4 or more double bonds and containing O or S 24 Heteroalkenyl or straight chain C2-C with 1, 2, 3, 4 or more triple bonds and containing O or S 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0182] In some embodiments, the present disclosure provides R and R 10 are each independently linear C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C20 , C 21 , C 22 , C 23 , or C 24 Alkynyl; or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0183] In some embodiments, the present disclosure provides R and R 10 Each independently branches C3-C 24 Alkyl or branched C3-C with 1, 2, 3, 4 or more double bonds 24 Alkenyl or branched C4-C with 1, 2, 3, 4 or more triple bonds 24 Alkynyl or branched C3-C containing O or S 24 Heteroalkyl or branched C3-C with 1, 2, 3, 4, or more double bonds and containing O or S 24 Heteroalkenyl or branched C4-C with 1, 2, 3, 4, or more triple bonds and containing O or S 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0184] In some embodiments, the present disclosure provides R and R 10 are independently branched into C3, C4, C5, C6, C7, C8, C9, and C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24Alkenyl, or branched C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20, C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0185] In some embodiments, the present disclosure provides R and / or R 10 is hydroxyl, halogen, =O, =S, cyano, cyclohydrocarbyl, aryl, heterocycle, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 Substituted with, C1-C 20 Alkyl (e.g., substituted C-C 10 Alkyl, substituted C2-C8 alkyl, substituted C7-C 18 alkyl), C1-C 16 Alkenyl (e.g., substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C5 alkenyl, substituted C6 alkenyl), or C5-C 16 Alkynyl (e.g., substituted C5-C 12 Alkynyl, substituted C 10 alkynyl), During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0186] In some embodiments, the present disclosure provides R and / or R 10 are each independently, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13C(=O)OR 14 When substituted with R 13 and / or R 14 is substituted R8 or R 10 and a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0187] In some embodiments, the present disclosure provides R and / or R 10 are each independently substituted aryl, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0188] In some embodiments, R or R 10 teeth [ka] and alkyl substituted phenyl such as:

[0189] In some embodiments, the present disclosure provides R and R 10 are each independently [ka] The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0190] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R6 is independently C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbyl, or C1, C2, C3, C4, C5, C6, C7, or C8 heterohydrocarbyl.

[0191] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R6 is independently C1-C8 alkyl, or C2-C8 alkenyl having one, two or more double bonds, or C2-C8 alkynyl having one, two or more triple bonds.

[0192] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R6 is independently C1, C2, C3, C4, C5, C6, C7, or C8 alkyl.

[0193] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each R6 is independently unsubstituted C1-C8 alkyl, or unsubstituted C2-C8 alkenyl, or unsubstituted C2-C8 alkynyl, or unsubstituted C1-C8 heteroalkyl, or unsubstituted C2-C8 heteroalkenyl, or unsubstituted C2-C8 heteroalkynyl. For example, each R6 is independently unsubstituted C1-C5 alkyl, unsubstituted C1-C3 alkyl, or unsubstituted C1 alkyl.

[0194] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein at least one of the R6 groups is a substituted C1-C8 alkyl, or a substituted C2-C8 alkenyl, or a substituted C2-C8 alkynyl, for example, one of the R6 groups is a substituted C1-C5 alkyl, a substituted C1-C3 alkyl, or a substituted C3 alkyl.

[0195] In some embodiments, the present disclosure provides a method for forming a ring structure in which at least one of the R groups is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, —R 14 , -R 13 OR 14 , -R 13SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0196] In some embodiments, the present disclosure provides a method for treating a cancer, wherein R6 is -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 When R is C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl substituted with 13 and / or R 14 may be bonded to the C atom of the substituted R6 to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0197] In some embodiments, the present disclosure provides: A 13 and A 14 are each independently C1, C2, C3, C4, C5, C6, C7, or C8 hydrocarbylene, or C1, C2, C3, C4, C5, C6, C7, or C8 heterohydrocarbylene, or a bond, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, A 13 and A 14 are each independently a bond.

[0198] In some embodiments, the present disclosure provides a 13 and A 14 are each independently a C1-C8 alkylene, a C2-C8 alkenylene having one, two or more double bonds, or a C2-C8 alkynylene having one, two or more triple bonds, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0199] In some embodiments, the present disclosure provides: Each A 13 and each A 14 are independently C1-C8 alkylene, C2-C8 alkenylene, or C2-C8 alkynylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0200] In some embodiments, the present disclosure provides 13 and / or each A 14 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A is unsubstituted C1-C8 alkylene, unsubstituted C2-C8 alkenylene, or unsubstituted C2-C8 alkynylene. 13 and A 14 are each independently an unsubstituted C2-C5 alkylene or an unsubstituted C3-C4 alkylene.

[0201] In some embodiments, the present disclosure provides a 13 Group and / or A 14 Provided is an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein at least one of the groups is a substituted C1-C8 alkylene, or a substituted C2-C8 alkenylene, or a substituted C2-C8 alkynylene.

[0202] In some embodiments, the present disclosure provides a13 Group and / or A 14 At least one of the groups is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 C1-C8 alkylene, C2-C8 alkenylene, or C2-C8 alkynylene, substituted with During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0203] In some embodiments, the present disclosure provides a 13 and / or A 14 But -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 When R is C1-C8 alkylene, C2-C8 alkenylene, or C2-C8 alkynylene substituted with 13 and / or R 14 is the substituted A 13 or A 14 and a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0204] In some embodiments, the present disclosure provides R and R 11 are independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Hydrocarbyl, or C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is a heterohydrocarbyl.

[0205] In some embodiments, the present disclosure provides that each R9 is independently C1-C 12 Alkyl (e.g., C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g., C5-C 12 alkenyl, C5-C8 alkenyl, C6 alkenyl), or C5-C 16 Alkynyl (e.g., C9-C 11 Alkynyl, C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0206] In some embodiments, the present disclosure provides that each R is an unsubstituted C-C 12Alkyl (e.g., unsubstituted C3-C9 alkyl, unsubstituted C5-C8 alkyl, unsubstituted C6 alkyl, unsubstituted C7 alkyl), unsubstituted C5-C 16 Alkenyl (e.g., unsubstituted C5-C 12 alkenyl, unsubstituted C5-C8 alkenyl, unsubstituted C6 alkenyl), or unsubstituted C5-C 16 Alkynyl (e.g., unsubstituted C9-C 11 Alkynyl, unsubstituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0207] In some embodiments, the present disclosure provides that at least one of the A groups is a substituted C-C 12 Alkyl (e.g., substituted C3-C9 alkyl, substituted C5-C8 alkyl, substituted C6 alkyl, substituted C7 alkyl), substituted C5-C 16 Alkenyl (e.g., substituted C5-C 12 alkenyl, substituted C5-C8 alkenyl, substituted C6 alkenyl), or substituted C5-C 16 Alkynyl (e.g., substituted C9-C 11 Alkynyl, substituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0208] In some embodiments, the present disclosure provides that each R 11 are independent, C1-C 12 Alkyl (e.g., C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g., C5-C 12 alkenyl, C5-C8 alkenyl, C6 alkenyl), or C5-C 16 Alkynyl (e.g., C9-C 11 Alkynyl, C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0209] In some embodiments, the present disclosure provides that each R 11 Unsubstituted C1-C 12 Alkyl (e.g., unsubstituted C3-C9 alkyl, unsubstituted C5-C8 alkyl, unsubstituted C6 alkyl, unsubstituted C7 alkyl), unsubstituted C5-C 16 Alkenyl (e.g., unsubstituted C5-C 12 alkenyl, unsubstituted C5-C8 alkenyl, unsubstituted C6 alkenyl), or unsubstituted C5-C 16 Alkynyl (e.g., unsubstituted C9-C 11 Alkynyl, unsubstituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0210] In some embodiments, the present disclosure provides the method of claim 1. 11 At least one of the groups is a substituted C-C 12 Alkyl (e.g., substituted C3-C9 alkyl, substituted C5-C8 alkyl, substituted C6 alkyl, substituted C7 alkyl), substituted C5-C 16 Alkenyl (e.g., substituted C5-C 12 Alkenyl, substituted C5-C8 alkenyl, substituted C6 alkenyl), substituted C5-C 16 Alkynyl (e.g., substituted C9-C 11 Alkynyl, substituted C 10 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein R is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,

[0211] In some embodiments, the present disclosure provides R and R 11 are each independently linear C1-C 24 Alkyl, straight chain C2-C with 1, 2, 3, 4 or more double bonds 24 Alkenyl, straight chain C2-C with 1, 2, 3, 4 or more triple bonds 24 Alkynyl, straight chain C1-C containing O or S 24Heteroalkyl, straight chain C2-C with 1, 2, 3, 4 or more double bonds and containing O or S 24 Heteroalkenyl or straight chain C2-C with 1, 2, 3, 4 or more triple bonds and containing O or S 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0212] In some embodiments, the present disclosure provides R and R 11 are each independently linear C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C21 , C 22 , C 23 , or C 24 Alkynyl; or straight chain C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkenyl, or straight chain C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0213] In some embodiments, the present disclosure provides R and R 11Each independently branches C3-C 24 Alkyl or branched C3-C with 1, 2, 3, 4 or more double bonds 24 Alkenyl or branched C4-C with 1, 2, 3, 4 or more triple bonds 24 Alkynyl or branched C3-C containing O or S 24 Heteroalkyl or branched C3-C with 1, 2, 3, 4, or more double bonds and containing O or S 24 Heteroalkenyl or branched C4-C with 1, 2, 3, 4, or more triple bonds and containing O or S 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0214] In some embodiments, the present disclosure provides R and R 11 are independently branched into C3, C4, C5, C6, C7, C8, C9, and C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkyl or branched C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkenyl, or branched C4, C5, C6, C7, C8, C9, C10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Alkynyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkyl or branched C3, C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , or C 24 Heteroalkenyl or branched C4, C5, C6, C7, C8, C9, C containing O or S 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22, C 23 , or C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0215] In some embodiments, the present disclosure provides the R group and / or the R 11 At least one of is hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 substituted with, group, C1-C 12 Alkyl (C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl), C5-C 16 Alkenyl (e.g., C5-C 12 Alkenyl, C5-C8 alkenyl, C6 alkenyl), substituted C5-C 16 Alkynyl (e.g., C9-C 11 Alkynyl, C 10 alkynyl), During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0216] In some embodiments, the present disclosure provides R and / or R 11 are -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 C1-C 12C5-C substituted with alkyl (C3-C9 alkyl, C5-C8 alkyl, C6 alkyl, C7 alkyl) 16 Alkenyl (e.g., C5-C 12 alkenyl, C5-C8 alkenyl, C6 alkenyl), or substituted C5-C 16 Alkynyl (e.g., C9-C 11 Alkynyl, C 10 alkynyl), when R 13 and / or R 14 is a substituted R or R 11 and a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0217] In some embodiments, the present disclosure provides an R group and / or R 11 In some embodiments, the amino lipid compound is represented by the formula (II-I) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein at least one of the groups R and R is independently substituted aryl. 11 teeth, [ka] and the like.

[0218] In some embodiments, the present disclosure provides R and R 11 are each independently [ka] and preferably [ka] The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0219] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each Z8 is independently a bond.

[0220] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein each Z9 is independently a bond.

[0221] In some embodiments, the present disclosure provides a compound in which R is H, C-C 24 Hydrocarbyl, C1-C 24 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is heterohydrocarbyl, Z6R8, or —CH(OR9)2. In some embodiments, R1 is -CH(OR9)2.

[0222] In some embodiments, the present disclosure provides a compound wherein R is H, C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, Z7R 10 , or -CH(OR 11 )2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. In some embodiments, R2 is —CH(OR 11 )2.

[0223] In some embodiments, the present disclosure provides an aryl group wherein R and / or R are hydroxyl, halogen, ═O, ═S, cyano, cyclohydrocarbyl, aryl, heterocycle, —R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 Substituted with, C1-C 24 Alkyl (e.g., C5-C 16 Alkyl, C6-C 14 Alkyl, C6-C 12 alkyl), C2-C 24 Alkenyl (e.g., C5-C 16 Alkenyl, C6-C 14 Alkenyl, C6-C 12 alkenyl), or C2-C 24 Alkynyl (e.g., C5-C 16 Alkynyl, C6-C 14 Alkynyl, C6-C 12 Alkynyl, C 10 alkynyl), During the ceremony, Each R 13 are independent of each other, C1-C 12 Alkylene, C2-C with 1, 2, 3 or more double bonds 12 Alkenylene, C2-C with 1, 2, 3 or more triple bonds 12 Alkynylene, C1-C containing S or O 12 Heteroalkylene, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenylene or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 is heteroalkynylene; Each R 14 are independently H, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is heteroalkynyl.

[0224] In some embodiments, the present disclosure provides a compound in which R and / or R are each independently -R 14 , -R 13 OR 14 , -R 13 SR 14 , -R 13 OC(=O)OR 14 , -R 13 OC(=O)SR 14 , -R 13 C(=O)N(R 14 )2, -R 13 OC(=O)R 14 , -R 13 SC(=O)OR 14 , -R 13 N(R 14 )C(=O)R 14 , or -R 13 C(=O)OR 14 C1-C substituted with 24 Alkyl (e.g., C5-C 16 Alkyl, C6-C 14 Alkyl, C6-C 12 alkyl), C2-C 24 Alkenyl (e.g., C5-C 16 Alkenyl, C6-C 14 Alkenyl, C6-C 12 alkenyl), or C2-C 24 Alkynyl (e.g., C5-C 16 Alkynyl, C6-C 14 Alkynyl, C6-C 12 Alkynyl, C 10 alkynyl), when R 13 and / or R14 may be bonded to the C atom of the substituted R1 or R2 to form a 3-membered ring, a 4-membered ring, a 5-membered ring, or a 6-membered ring, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0225] In some embodiments, each R 14 may also independently be substituted aryl, substituted cyclohydrocarbyl, or substituted heterocyclyl. In some embodiments, R 14 is alkyl-substituted aryl.

[0226] In some embodiments, R 14 teeth, [ka] and the like.

[0227] In some embodiments, R 14 is an unsubstituted cycloalkyl such as cyclobutyl, cyclopentyl, or cyclohexyl.

[0228] In some embodiments, the present disclosure provides a method for treating a hydroxyl-substituted C6-C 14 Alkyl, hydroxyl substituted C6-C 12 Alkyl, hydroxyl substituted C 10 Hydroxyl-substituted C5-C alkyl 16 In some embodiments, R and R are independently selected from the group consisting of alkyl, alkyl, aryl ... [ka] C etc. 10 It is alkyl.

[0229] In some embodiments, the present disclosure provides a compound wherein R and R are each independently: [ka]

[0230] [ka]

[0231] [ka] and preferably [ka] The present invention provides an amino lipid compound represented by the above formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0232] In some embodiments, the present disclosure provides a compound in which R1 is Z6R8 or -CH(OR9)2 and R2 is Z7R 10 or -CH(OR 11 )2, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0233] In some embodiments, the amino lipid compound represented by formula (III), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-Ia): [ka] During the ceremony, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl; A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl; A3 is C1-C5 hydrocarbylene or a bond; A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R1, R2, and A 12 is as defined in formula (II-I).

[0234] The present disclosure provides amino lipid compounds represented by formula (II-Ia) above, or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprising one or more of the following characteristics, where applicable:

[0235] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-Ia), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2 are each independently H.

[0236] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ia) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2 are each independently C1, C2, C3, C4, or C5 hydrocarbyl, or C1, C2, C3, C4, or C5 heterohydrocarbyl.

[0237] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-Ia), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2 are each independently C1-C5 alkyl, or C2-C5 alkenyl having one or two double bonds, or C2-C5 alkynyl having one or two triple bonds, or C1-C5 heteroalkyl containing S or O, or C2-C5 heteroalkenyl having one or two double bonds and containing S or O, or C2-C5 heteroalkynyl having one or two triple bonds and containing S or O.

[0238] In some embodiments, the present disclosure provides that A1 and A2 are each independently selected from hydroxyl, cyano, phenyl, C3-C7 cyclohydrocarbyl, C3-C7 cyclohydrocarbyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, -OR 12 , -C(=O)R 12 , -C(=O)SR 12 , -OC(=O)R 12 , -OC(=O)OR 12 , -N(R 12 )2, -C(=O)N(R 12 )2, C(=S)N(R 12 )2, -S(=O)2R 12 , -S(=O)2N(R 12 )2, -OC(=O)N(R 12 )2, -CH(NR 12 )N(R 12 )2, -C(NR 12 )2R 12 , -C(=O)N(R 12 ) OR 12 , -CH(R 12 )N(R 12 )2C(=O)OR 12 , -C(R 12 )3, -N(R 12 )C(=O)R 12 , -N(R 12 )C(=O)OR 12 , -N(R 12 )S(=O)2R 12 , -N(R 12 )C(=O)N(R 12 )2, -N(R 12 )C(=S)N(R 12 )2, -N(R 12 )C(NR 12 )N(R 12 )2, -N(R 12 )C(CHR 12 )N(R 12 )2, -N(OR 12 )C(=O)R12 , -N(OR 12 )S(=O)2R 12 , -N(OR 12 )C(=O)OR 12 , -N(OR 12 )C(=O)N(R 12 )2, -N(OR 12 )C(=S)N(R 12 )2, -N(OR 12 )C(NR 12 )N(R 12 )2, -N(OR 12 )C(CHR 12 )N(R 12 )2, -OP(=O)(OR 12 )2, -P(=O)(OR 12 )2, or a 3- to 7-membered cycloaliphatic ring and a 3- to 7-membered heterocycle each containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2, -C(=NO-CH3)N(R 12 )2, -C(=N-SO2-NH2)N(R 12 )2, -C(=CH-NO2)N(R 12 )2, or -C(=O)OR 12 (Each R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-Ia), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, optionally substituted with (R- ...

[0239] In some embodiments, the present disclosure provides compounds wherein A and A each independently contain 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and are selected from C-C alkyl, ═O, —C-C alkylene-hydroxyl, —C(═O)N(R 15 ) C3-C7 cyclohydrocarbyl optionally substituted with 2; 8-10 membered bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur and optionally substituted with C1-C5 alkyl, hydroxyl; [ka] (In the formula, each R 15 is independently H or C1-C3 alkyl, and d is 0, 1, 2, 3, 4, or 5), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0240] In some embodiments, the present disclosure provides that A1 and A2 are each independently: [ka] The present invention provides an amino lipid compound represented by the above formula (II-Ia), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0241] In some embodiments, the present disclosure provides that A1 and A2 are also each independently: [ka] (wherein a is 1, 2, 3, 4, or 5; preferably, a is 1, 2, or 3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0242] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ia) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is a bond.

[0243] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ia) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1, C2, C3, C4, or C5 hydrocarbylene. In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-Ia), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds.

[0244] In some embodiments, the present disclosure provides: [ka] but [ka] (wherein c is 1, 2, 3, 4, or 5; preferably, c is 2, 3, or 4; preferably, c is 2 or 3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0245] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-Ib): [ka] During the ceremony, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene; A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene; A3 is C1-C5 hydrocarbylene or a bond; A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing heterocycle; A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R1, R2, and A 12 is as defined in formula (II-I).

[0246] The present disclosure provides amino lipid compounds represented by formula (II-Ib) above, or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprising one or more of the following characteristics, where applicable:

[0247] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ib) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2 are each independently C1, C2, C3, C4, or C5 hydrocarbylene, or C1, C2, C3, C4, or C5 heterohydrocarbylene.

[0248] In some embodiments, the present disclosure provides: Provided is an amino lipid compound represented by the above formula (II-Ib), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2 are each independently C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds, or C1-C5 heteroalkylene containing S or O, or C2-C5 heteroalkenylene having one or two double bonds and containing S or O, or C2-C5 heteroalkynylene having one or two triple bonds and containing S or O.

[0249] In some embodiments, the present disclosure provides that A1 and A2 are each independently selected from hydroxyl, cyano, phenyl, C3-C7 cyclohydrocarbyl, C3-C7 cyclohydrocarbyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, -OR 12 , -C(=O)R 12 , -C(=O)SR 12 , -OC(=O)R 12 , -OC(=O)OR 12 , -N(R 12 )2, -C(=O)N(R 12 )2, C(=S)N(R 12 )2, -S(=O)2R 12 , -S(=O)2N(R 12 )2, -OC(=O)N(R 12 )2, -CH(NR 12 )N(R 12 )2, -C(NR 12 )2R 12 , -C(=O)N(R 12 ) OR 12 , -CH(R 12 )N(R 12 )2C(=O)OR 12 , -C(R 12 )3, -N(R 12 )C(=O)R 12 , -N(R 12 )C(=O)OR 12 , -N(R 12 )S(=O)2R 12 , -N(R 12 )C(=O)N(R 12 )2, -N(R 12 )C(=S)N(R 12 )2, -N(R 12 )C(NR 12 )N(R 12 )2, -N(R 12 )C(CHR 12 )N(R 12 )2, -N(OR 12 )C(=O)R12 , -N(OR 12 )S(=O)2R 12 , -N(OR 12 )C(=O)OR 12 , -N(OR 12 )C(=O)N(R 12 )2, -N(OR 12 )C(=S)N(R 12 )2, -N(OR 12 )C(NR 12 )N(R 12 )2, -N(OR 12 )C(CHR 12 )N(R 12 )2, -OP(=O)(OR 12 )2, -P(=O)(OR 12 )2, or a 3- to 7-membered cycloaliphatic ring and a 3- to 7-membered heterocycle each containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2, -C(=NO-CH3)N(R 12 )2, -C(=N-SO2-NH2)N(R 12 )2, -C(=CH-NO2)N(R 12 )2, or -C(=O)OR 12 (Each R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-Ib), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, optionally substituted with (R- ...

[0250] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ib) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is a bond.

[0251] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ib) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1, C2, C3, C4, or C5 hydrocarbylene.

[0252] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-Ib), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds.

[0253] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ib) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycle.

[0254] In some embodiments, A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 3-, 4-, 5-, or 6-membered heterocycle. In some embodiments, A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 4-, 5-, or 6-membered heterocycle.

[0255] In some embodiments, the present disclosure provides: [ka] but [ka] (wherein c is 1, 2, 3, 4, or 5; preferably, c is 2, 3, or 4; preferably, c is 2 or 3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0256] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-Ic): [ka] During the ceremony, A1 is C1-C5 hydrocarbylene, or C1-C5 heterohydrocarbylene; A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl; A3 is C1-C5 hydrocarbylene; A1 and A3 together with the nitrogen atom to which they are both attached form an N-containing heterocycle; A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R1, R2, and A 12 is as defined in formula (II-I).

[0257] The present disclosure provides amino lipid compounds represented by formula (II-Ic) above, or pharmaceutically acceptable salts thereof, or stereoisomers thereof, which, where applicable, comprise one or more of the following characteristics:

[0258] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A2 is H.

[0259] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 is C1, C2, C3, C4, or C5 hydrocarbylene, or C1, C2, C3, C4, or C5 heterohydrocarbylene.

[0260] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 is C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds, or C1-C5 heteroalkylene containing S or O, or C2-C5 heteroalkenylene having one or two double bonds and containing S or O, or C2-C5 heteroalkynylene having one or two triple bonds and containing S or O.

[0261] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A2 is C1, C2, C3, C4, or C5 hydrocarbyl, or C1, C2, C3, C4, or C5 heterohydrocarbyl.

[0262] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A2 is C1-C5 alkyl, or C2-C5 alkenyl having one or two double bonds, or C2-C5 alkynyl having one or two triple bonds, or C1-C5 heteroalkyl containing S or O, or C2-C5 heteroalkenyl having one or two double bonds and containing S or O, or C2-C5 heteroalkynyl having one or two triple bonds and containing S or O.

[0263] In some embodiments, the present disclosure provides that A1 and A2 are each independently selected from hydroxyl, cyano, phenyl, C3-C7 cyclohydrocarbyl, C3-C7 cyclohydrocarbyl containing 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, -OR 12 , -C(=O)R 12 , -C(=O)SR 12 , -OC(=O)R 12 , -OC(=O)OR 12 , -N(R 12 )2, -C(=O)N(R 12 )2, C(=S)N(R 12 )2, -S(=O)2R 12 , -S(=O)2N(R 12 )2, -OC(=O)N(R 12 )2, -CH(NR 12 )N(R 12 )2, -C(NR 12 )2R 12 , -C(=O)N(R 12 ) OR 12 , -CH(R 12 )N(R 12 )2C(=O)OR 12 , -C(R 12 )3, -N(R 12 )C(=O)R 12 , -N(R 12 )C(=O)OR 12 , -N(R 12 )S(=O)2R 12 , -N(R 12 )C(=O)N(R 12 )2, -N(R 12 )C(=S)N(R 12 )2, -N(R 12 )C(NR 12 )N(R 12 )2, -N(R 12 )C(CHR 12 )N(R 12 )2, -N(OR 12 )C(=O)R12 , -N(OR 12 )S(=O)2R 12 , -N(OR 12 )C(=O)OR 12 , -N(OR 12 )C(=O)N(R 12 )2, -N(OR 12 )C(=S)N(R 12 )2, -N(OR 12 )C(NR 12 )N(R 12 )2, -N(OR 12 )C(CHR 12 )N(R 12 )2, -OP(=O)(OR 12 )2, -P(=O)(OR 12 )2, or 3- to 7-membered cycloaliphatic rings and 3- to 7-membered heterocycles each containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, -C(=N-CN)N(R 12 )2, -C(=NO-CH3)N(R 12 )2, -C(=N-SO2-NH2)N(R 12 )2, -C(=CH-NO2)N(R 12 )2, or -C(=O)OR 12 (Each R 12 are independently hydrogen, C1-C 12 Alkyl, C2-C with 1, 2, 3 or more double bonds 12 Alkenyl, C2-C with 1, 2, 3 or more triple bonds 12 Alkynyl, C1-C containing S or O 12 Heteroalkyl, C2-C with 1, 2, 3 or more double bonds and containing S or O 12 Heteroalkenyl or C2-C with 1, 2, 3, or more triple bonds and containing S or O 12 The present invention provides an amino lipid compound represented by the above formula (II-Ic), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, optionally substituted with (R- ...

[0264] In some embodiments, the present disclosure provides compounds wherein A and A each independently contain 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and are selected from C-C alkyl, ═O, —C-C alkylene-hydroxyl, —C(═O)N(R 15 ) C3-C7 cyclohydrocarbyl optionally substituted with 2; 8-10 membered bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur and optionally substituted with C1-C5 alkyl, hydroxyl; [ka] (Each R 15 is independently H or C1-C3 alkyl, and d is 0, 1, 2, 3, 4, or 5), or a pharmaceutically acceptable salt, or stereoisomer thereof.

[0265] In some embodiments, the present disclosure provides a method for treating a heart disease, comprising administering to a patient a therapeutically effective amount of at least one of: [ka] The present invention provides an amino lipid compound represented by the above formula (II-Ic), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

[0266] In some embodiments, the present disclosure provides that A2 is [ka] (wherein a is 1, 2, 3, 4, or 5; preferably, a is 1, 2, or 3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0267] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1, C2, C3, C4, or C5 hydrocarbylene.

[0268] In some embodiments, the present disclosure provides an amino lipid compound represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A3 is C1-C5 alkylene, or C2-C5 alkenylene having one or two double bonds, or C2-C5 alkynylene having one or two triple bonds.

[0269] In some embodiments, the present disclosure provides amino lipid compounds represented by formula (II-Ic) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein A1 and A3, together with the nitrogen atom to which they are both attached, form an N-containing 3-, 4-, 5-, 6-, 7-, or 8-membered heterocycle.

[0270] In some embodiments, A1 and A3 together with the nitrogen atom to which they are both attached form an N-containing 3-, 4-, 5-, or 6-membered heterocycle. In some embodiments, A1 and A3 together with the nitrogen atom to which they are both attached form an N-containing 4-, 5-, or 6-membered heterocycle.

[0271] In some embodiments, the present disclosure provides: [ka] but [ka] (wherein c is 1, 2, 3, 4, or 5; preferably, c is 2, 3, or 4; preferably, c is 2 or 3), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0272] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-Id): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1, R2, and A 12 is as defined in formula (II-I).

[0273] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-Ie): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1, R2, and A 12 is as defined in formula (II-I).

[0274] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-II): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R2, R9, and A 12 is as defined in formula (II-I).

[0275] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-IIa): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R2, R9, and A 12 is as defined in formula (II-I).

[0276] The present disclosure provides amino lipid compounds represented by formula (II-IIa) above, or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprising one or more of the following characteristics, where applicable:

[0277] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is a hydrocarbylene. In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is alkylene. In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is alkenylene. In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is alkynylene. In some embodiments, A5 and A6 are not methylene.

[0278] In some embodiments, Z is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R)-, -N(R)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R)C(=O)O-, -OC(=O)N(R)-, -N(R)C(=O)N(R)-, -SC(=O)N(R)-, -N(R)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-.

[0279] In some embodiments, Z2 is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-.

[0280] In some embodiments, A5 and A6 are each independently a C1, C2, C3, C4, C5, or C6 hydrocarbylene or a bond. In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, or C6 alkylene or a bond. In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, or C6 alkenylene or a bond. In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, or C6 alkynylene or a bond. In some embodiments, A5 and A6 are each independently a C1, or a C2 hydrocarbylene or a bond. In some embodiments, A5 and A6 are each independently a C1 or C2 alkylene or a bond. In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond. In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond.

[0281] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-IIb): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R2, R9, and A 12 is as defined in formula (II-I).

[0282] In some embodiments, the amino lipid compound represented by formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-III): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, X, R9, R 11 , and A 12 is as defined in formula (II-I).

[0283] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-IIIa): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, R 11 , and A 12 is as defined in formula (II-I).

[0284] The present disclosure provides amino lipid compounds represented by formula (II-IIIa) above, or pharmaceutically acceptable salts thereof, or stereoisomers thereof, which, where applicable, comprise one or more of the following characteristics:

[0285] In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is a hydrocarbylene. In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is alkylene. In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is alkenylene. In some embodiments, A 12 C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 It is alkynylene. In some embodiments, neither A5 nor A6 is methylene.

[0286] In some embodiments, Z is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R)-, -N(R)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R)C(=O)O-, -OC(=O)N(R)-, -N(R)C(=O)N(R)-, -SC(=O)N(R)-, -N(R)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-.

[0287] In some embodiments, Z2 is -C(=O)O-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-.

[0288] In some embodiments, A5 and A6 are each independently a C1, C2, C3, C4, C5, or C6 hydrocarbylene or a bond. In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, or C6 alkylene or a bond. In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, or C6 alkenylene or a bond. In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, or C6 alkynylene or a bond.

[0289] In some embodiments, A5 and A6 are each independently a C1, or a C2 hydrocarbylene or a bond. In some embodiments, A5 and A6 are each independently a C1 or C2 alkylene, or a bond. In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond. In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond.

[0290] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-IIIb): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, R 11 , and A 12 is as defined in formula (II-I).

[0291] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-IVa) or (II-IVb): [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9, R 11 , and A 12 is as defined in formula (II-I).

[0292] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-IVa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, as described above: During the ceremony, A1, A2, and A3 are one of the following: (1) In the absence of a dashed line connecting A1 and A2 and a dashed line connecting A1 and A3, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond; (2) If the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (3) If the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is H, C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene, and A1, A2, and A3, together with the nitrogen atom to which they are all bonded, form a nitrogen-containing spiro heterocycle, a nitrogen-containing fused heterocycle, or a nitrogen-containing bridged heterocycle; A4 is a C1-C5 hydrocarbylene or a bond; A5, A6, A7, A8, and A 12 are independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; Z1 and Z2 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; each R6 is independently H or C1-C8 hydrocarbyl; Each R9 and each R 11 are independently C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; each A9 is a C1-C8 hydrocarbylene or a bond; Each A 10 and each A 11 are each independently C1-C8 hydrocarbyl; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is alkylene, alkenylene, or alkynylene; Preferably, the heterohydrocarbyl is heteroalkyl, heteroalkenyl, or heteroalkynyl; Preferably, the heterohydrocarbylene is a heteroalkylene, heteroalkenylene, or heteroalkynylene.

[0293] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-Va), (II-Vb), (II-Vc), (II-Vd), (II-Ve), (II-Vf), (II-Vg), or (II-Vh): [ka]

[0294] [ka] In the formula, A1, A2, A3, A4, A5, A6, A7, A8, R9, R 11 , and A 12 is as defined in formula (II-I).

[0295] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-VIa): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1, and R2 are as defined in formula (II-I).

[0296] In some embodiments, the present disclosure provides an amino lipid compound of formula (II-VIa) above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: During the ceremony, A1, A2, and A3 are one of the following: (1) In the absence of a dashed line connecting A1 and A2 and a dashed line connecting A1 and A3, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond; (2) If the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (3) If the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene, and A1, A2, and A3, together with the nitrogen atom to which they are all bonded, form a nitrogen-containing spiro heterocycle, a nitrogen-containing fused heterocycle, or a nitrogen-containing bridged heterocycle; A4 is a C1-C5 hydrocarbylene or a bond; A5, A6, A7, and A8 are each independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; Z1 and Z2 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; Y1 is -Z3C(=O)Z4-, -N(R5)-, -Z3C(=S)Z4-, -OS(=O)2O-, -OS(=O)O-, -OS(=O)2 NH-, -NHS(=O)2NH-, -NHS(=O)2-, -S(=O)2NH-, -S(=O)2O-, -OS(=O)2-, -OP(=O )O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -O-, -S-, -NHS(=O)2O-, -NHP(=O)O-, -OP(=O)NH-, -NHP(=O)(OH)O-, -OP(=O)(OH)NH-, -OC(=O)S-, or -SC(=O)O-; X is C or N; R1 is H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, Z6R8, -C(R6)(OA 13 Z8R9)2, -C(R6)(SA 13 Z8R9)2, or -C(R6)(SA 13 Z8R9)(OA 13 Z8R9); R2 is H, C1-C 24 Hydrocarbyl, C1-C 24 Heterohydrocarbyl, Z7R 10 , -C(R6)(OA 14 Z9R 11 )2, -C(R6)(SA 14 Z9R 11 )2, or -C(R6)(SA 14 Z9R 11 )(OA 14 Z9R 11 ) and; Z3 and Z4 are each independently -O-, -N(R6)-, -S-, or a bond; Z6 and Z7 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; R5 is -C(=O)A9Z5A 10 , -C(=O)A 11 , H, or C1-C8 hydrocarbyl; Z5 is -O- or -S-; Z8 and Z9 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11)-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, -NHS(=O)2O-, or a bond; each R6 is independently H or C1-C8 hydrocarbyl; R8 and R 10 are independently H, C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; Each R9 and each R 11 are independently C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; each A9 is a C1-C8 hydrocarbylene or a bond; Each A 10 and each A 11 are each independently C1-C8 hydrocarbyl; Each A 13 and each A 14 are each independently C1-C8 hydrocarbylene, C1-C8 heterohydrocarbylene, or a bond; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is alkylene, alkenylene, or alkynylene; Preferably, the heterohydrocarbyl is heteroalkyl, heteroalkenyl, or heteroalkynyl; Preferably, the heterohydrocarbylene is a heteroalkylene, heteroalkenylene, or heteroalkynylene.

[0297] In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C16 , C 17 , or C 18 A hydrocarbylene or a bond, neither of which is methylene. In some embodiments, A5 and A6 are each independently a C1, or a C2 hydrocarbylene or a bond, and neither is methylene. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 hydrocarbylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is a hydrocarbylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is a hydrocarbylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is a hydrocarbylene. In some embodiments, A5 and A6 are each independently C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 alkylene, or a bond, neither of which is methylene.

[0298] In some embodiments, A5 and A6 are each independently a C1 or C2 alkylene or a bond, and neither is methylene. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is alkylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is alkylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is alkylene. In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 alkenylene, or a bond.

[0299] In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkenylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is alkenylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is alkenylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is alkenylene. In some embodiments, A5 and A6 are each independently C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , C 17 , or C 18 alkynylene, or a bond. In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkynylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is alkynylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is alkynylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is alkynylene.

[0300] In some embodiments, A1 and A2 are each independently C1-C5 alkyl, preferably C1-C3 alkyl such as methyl, ethyl, n-propyl, or isopropyl; A3 is C1-C5 alkylene, preferably C2-C4 alkylene such as —(CH2)2—, —(CH2)3—, or —(CH2)4—; Y1 is —Z3C(═O)Z4—, preferably —N(R6)C(═O)N(R6)—, more preferably —N(H)C(═O)N(H)—; Z1 and Z2 are each independently —C(═O)O— or —OC(═O)—; A7 and A8 are each independently a bond; R1 and R2 are each independently C1-C 24Hydrocarbyl, preferably C1-C 24 Alkyl, more preferably -C4H9, -C5H 11 , -CH 13 , -CH 15 , -CH 17 , -CH 19 , -CH(C4H9)2, -CH(C5H 11 )2, -CH(CH 13 )2, -CH(CH 15 )2, -CH(CH 17 )2, -CH(CH 19 )2, -CH2CH(CH 13 )(C4H9), etc. 12 Alkyl or branched C7-C 21 It is alkyl.

[0301] In some embodiments, the amino lipid compound represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIa-a): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, and R2 are as defined in formula (II-VIa).

[0302] In some embodiments, the amino lipid compound represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIa-b): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, and R 11 is as defined in formula (II-VIa).

[0303] In some embodiments, the amino lipid compound represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIa-c): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9, and R 11 is as defined in formula (II-VIa).

[0304] In some embodiments, the present disclosure provides an amino lipid compound represented by the above formula (II-VIa-c), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, During the ceremony A1, A2, and A3 are one of the following: (1) In the absence of a dashed line connecting A1 and A2 and a dashed line connecting A1 and A3, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond; (2) If the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (3) If the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, then A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both bonded, form a nitrogen-containing heterocycle; (4) When the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are bonds, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene, and A1, A2, and A3, together with the nitrogen atom to which they are all bonded, form a nitrogen-containing spiro heterocycle, a nitrogen-containing fused heterocycle, or a nitrogen-containing bridged heterocycle; A4 is a C1-C5 hydrocarbylene or a bond; A5, A6, A7, and A8 are each independently C1-C 18 Hydrocarbylene, C1-C 18 heterohydrocarbylene, or a bond; Z1 and Z2 each independently represent -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -SC(=O)N(R6)-, -N(R6)C(=O)S-, -N(C(=O)A9OA 10 )-, -N(C(=O)A9SA 10 )-, -N(C(=O)A 11 ), -N(A9OA 10 )-, -N(A9SA 10 )-, -N(A 11 )-, -OS(=O)O-, -OS(=O)2O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O)2NH-, or -NHS(=O)2O-; each R6 is independently H or C1-C8 hydrocarbyl; Each R9 and each R 11 are independently C1-C 24 Hydrocarbyl or C1-C containing O or S 24 is heterohydrocarbyl; each A9 is a C1-C8 hydrocarbylene or a bond; Each A 10 and each A 11 are each independently C1-C8 hydrocarbyl; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is alkylene, alkenylene, or alkynylene; Preferably, the heterohydrocarbyl is heteroalkyl, heteroalkenyl, or heteroalkynyl; Preferably, the heterohydrocarbylene is a heteroalkylene, heteroalkenylene, or heteroalkynylene.

[0305] The amino lipid compounds represented by formula (II-IVa), (II-VIa), or (II-VIa-c), or pharmaceutically acceptable salts thereof, or stereoisomers thereof, comprise one or more of the following characteristics, as applicable:

[0306] In some embodiments, A4 is a bond. In some embodiments, Y1 is -Z3C(=O)Z4- or -N(R5)-. In some embodiments, Y1 is -N(R6)C(=O)O-, -OC(=O)N(R6)-, or -OC(=O)O-. In some embodiments, Y 1 is —OC(═O)O—. In some embodiments, Y1 is -N(R6)C(=O)O- or -OC(=O)N(R6)-. In some embodiments, each R6 is independently H, or -OC(=O)R 14 , -C(=O)OR 14 , or -OR 14 is C1-C8 alkyl substituted with In some embodiments, Y is —N(R)C(═O)O— or —OC(═O)N(R)—, wherein each R is independently —OC(═O)R 14 , -C(=O)OR 14, or -OR 14 and C1-C8 alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl) substituted with.

[0307] In some embodiments, Y1 is -N(H)C(=O)O-. In some embodiments, Y 1 is —OC(═O)N(H)—. In some embodiments, Y1 is -N(R5)-. In some embodiments, Y is —N(C(═O)A9OA 10 )-. In some embodiments, Y is —N(C(═O)A 10 )-. In some embodiments, Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -C(=O)N(R6)-, -N(R6)C(=O)-, -N(R6)C(=O)O-, -OC(=O)N(R6)-, -N(R6)C(=O)N(R6)-, -C(=O)S-, -SC(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OS(=O)O-, -OS(=O)O-, -OP(=O)O-, -OP(=O)(OH)O-, or -OP(=O)(H)O-.

[0308] In some embodiments, Z1 and Z2 are each independently -C(=O)O-, -OC(=O)-, -OC(=O)O-, -N(H)C(=O)O-, or -OC(=O)N(H)-. In some embodiments, Z 1 and Z 2 are each independently —(C═O)O— or —O(C═O)—. In some embodiments, Z1 is -C(=O)O-. In some embodiments, Z1 is -OC(=O)-. In some embodiments, Z1 is -OC(=O)O-. In some embodiments, Z1 is -N(H)C(=O)O-. In some embodiments, Z1 is -OC(=O)N(H)-. In some embodiments, Z2 is -C(=O)O-. In some embodiments, Z2 is -OC(=O)-. In some embodiments, Z2 is -OC(=O)O-. In some embodiments, Z2 is -N(H)C(=O)O-. In some embodiments, Z2 is -OC(=O)N(H)-. In some embodiments, Z1 and Z2 are -C(=O)O-. In some embodiments, Z1 and Z2 are -OC(=O)-. In some embodiments, Z1 and Z2 are -OC(=O)O-. In some embodiments, Z1 and Z2 are -N(H)C(=O)O-. In some embodiments, Z1 and Z2 are -OC(=O)N(H)-. In some embodiments, Z 1 is —C(═O)O— and Z 2 is —OC(═O)—.

[0309] In some embodiments, A4 is a bond and Z1 and Z2 are -C(=O)O-. In some embodiments, A4 is a bond and Z1 and Z2 are -OC(=O)-. In some embodiments, A4 is a bond and Z1 and Z2 are -OC(=O)O-. In some embodiments, A4 is a bond and Z1 and Z2 are -N(H)C(=O)O-. In some embodiments, A4 is a bond and Z1 and Z2 are -OC(=O)N(H)-. In some embodiments, A4 is a bond, Z1 is -C(=O)O-, and Z2 is -OC(=O)-.

[0310] In some embodiments, A 12 is a C1-C3 alkylene, such as a C2-C3 alkylene. In some embodiments, A 12 is C1-C3 alkylene (for example, C1 alkylene), and A5 and A6 are each independently C3-C9 alkylene (for example, C4-C9 alkylene, C5-C9 alkylene, C6 alkylene, C7 alkylene, C8 alkylene).

[0311] In some embodiments, R1 is -C(R6)(OR9)2. In some embodiments, R1 is -C(H)(OR9)2. In some embodiments, R2 is -C(R6)(OR 11 )2. In some embodiments, R2 is —C(H)(OR 11 )2. In some embodiments, R2 is Z7R 10 is. In some embodiments, R2 is -C(=O)OR 10 is. In some embodiments, R2 is -OC(=O)R 10 is. In some embodiments, R2 is -OR 10 is. In some embodiments, R2 is -N(H)C(=O)R 10 is. In some embodiments, R2 is —C(═O)N(R6)R 10 is. In some embodiments, R2 is a substituted C5-C 16 Alkyl, substituted C6-C 14 Alkyl, substituted C6-C 12 Substituted C1-C such as alkyl 24 It is alkyl. In some embodiments, R2 is a hydroxyl-substituted C1-C 24 Alkyl, e.g., hydroxyl-substituted C-C 14Alkyl, hydroxyl substituted C6-C 12 Alkyl, hydroxyl substituted C 10 Hydroxyl-substituted C5-C alkyl 16 It is alkyl.

[0312] In some embodiments, R1 is -C(R6)(OR9)2 and R2 is -C(R6)(OR 11 )2. In some embodiments, R1 is -C(H)(OR9)2 and R2 is -C(H)(OR 11 )2. In some embodiments, R1 is -C(H)(OR9)2 and R2 is -C(=O)OR 10 is. In some embodiments, R1 is -C(H)(OR9)2 and R2 is -OC(=O)R 10 is. In some embodiments, R1 is -C(H)(OR9)2 and R2 is -OR 10 is. In some embodiments, R1 is -C(H)(OR9)2 and R2 is a hydroxyl-substituted C1-C 24 alkyl (e.g., R2 is a hydroxyl-substituted C5-C 16 Alkyl, hydroxyl substituted C6-C 14 Alkyl, hydroxyl substituted C6-C 12 Alkyl or hydroxyl substituted C 10 (It is alkyl).

[0313] In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -C(=O)OR 10 is. In some embodiments, Y is -OC(=O)O-, R is -C(H)(OR) and R is -OC(=O)R 10 is. In some embodiments, Y1 is -OC(=O)O-, R1 is -C(H)(OR9)2, and R2 is -OR 10is.

[0314] In some embodiments, Y is -OC(=O)O-, R is -C(H)(OR) and R is a substituted C-C 24 alkyl (e.g., R2 is a substituted C5-C 16 Alkyl, substituted C6-C 14 Alkyl, substituted C6-C 12 Alkyl or substituted C 10 (It is alkyl). In some embodiments, Y is -OC(=O)O-, R is -C(H)(OR) and R is a hydroxyl-substituted C-C 24 alkyl (e.g., R2 is a hydroxyl-substituted C5-C 16 Alkyl, hydroxyl substituted C6-C 14 Alkyl, hydroxyl substituted C6-C 12 Alkyl or hydroxyl substituted C 10 (It is alkyl). In some embodiments, Y is -OC(=O)O-, R is -C(H)(OR) and R is a hydroxyl-substituted C-C 24 alkyl (e.g., R2 is a hydroxyl-substituted C5-C 16 Alkyl, hydroxyl substituted C6-C 14 Alkyl, hydroxyl substituted C6-C 12 Alkyl or hydroxyl substituted C 10 A5 and A6 are each independently C2-C 10 Alkylene (eg, C5-C9 alkylene, C8 alkylene).

[0315] In some embodiments, Y is -OC(=O)O-, A and A are unsubstituted C-C alkylene (e.g., unsubstituted C-C alkylene), R is -C(H)(OR) and R is -C(=O)OR. 10 is. In some embodiments, Y is -OC(=O)O-, A and A are unsubstituted C-C alkylene (e.g., unsubstituted C-C alkylene), R is -C(H)(OR) and R is -OC(=O)R 10 is.

[0316] In some embodiments, Y1 is -N(H)C(=O)O-, R1 is -C(H)(OR9)2, and R2 is -C(H)(OR 11 )2. In some embodiments, Y1 is -OC(=O)N(H)-, R1 is -C(H)(OR9)2, and R2 is -C(H)(OR 11 )2. In some embodiments, Y is —N(C(═O)A9OA 10 )-, R1 is -C(H)(OR9)2, and R2 is -C(H)(OR 11 )2. In some embodiments, Y is —N(C(═O)A 10 )-, R1 is -C(H)(OR9)2, and R2 is -C(H)(OR 11 )2. In some embodiments, Y is —N(C(═O)A 10 )-, R1 is -C(H)(OR9)2, and R2 is a hydroxyl-substituted C1-C 24 alkyl (e.g., R2 is a hydroxyl-substituted C5-C 16 Alkyl, hydroxyl substituted C6-C 14 Alkyl, hydroxyl substituted C6-C 12 Alkyl or hydroxyl substituted C 10 It is alkyl.

[0317] In some embodiments, A9 is C1-C8 alkylene. In some embodiments, A9 is C1-C5 alkylene. In some embodiments, A9 is C1-C3 alkylene.

[0318] In some embodiments, A 10 is C1-C8 alkyl, such as C1, C2, C3, C5, or C8 alkyl. In some embodiments, R 10 is C1-C 24 Alkyl, C2-C 24 Alkenyl, or C2-C 24 It is alkynyl. In some embodiments, R 10 is a straight chain C2-C 10 It is alkyl. In some embodiments, R 10 is a straight chain C2-C8 alkyl.

[0319] In some embodiments, R 10 teeth, [ka] Branches such as C7-C 18 It is alkyl.

[0320] In some embodiments, R 10 is C5-C 16 It is alkenyl. In some embodiments, R 10 is C5-C 12 It is alkenyl. In some embodiments, R 10 is a C5-C8 alkenyl, such as a C5 or C6 alkenyl. In some embodiments, R 10 is C5-C 16 It is alkynyl. In some embodiments, R 10 is C 10 C5-C of alkynyl etc. 12 It is alkynyl. In some embodiments, R9 is C 10 C9-C of alkynyl etc. 11 It is alkynyl.

[0321] In some embodiments, R 14 is C1-C 12 It is alkyl. In some embodiments, R 14 is C1-C5 alkyl. In some embodiments, R 14 is a C2-C with one, two, three or more double bonds 12 It is alkenyl. In some embodiments, R 14 is a C4-C8 alkenyl having one double bond, such as a C6 alkenyl having one double bond.

[0322] In some embodiments, A5 and A6 are each independently C1-C 11 It is alkylene. In some embodiments, A5 and A6 are each independently C3-C 10 It is alkylene. In some embodiments, A5 and A6 are each independently a C4-C9 alkylene. In some embodiments, A5 and A6 are each independently a C5-C9 alkylene, such as a C6, C7, or C8 alkylene.

[0323] In some embodiments, A7 and A8 are each independently C1-C 12 It is alkylene. In some embodiments, A7 and A8 are each independently C5-C 10 It is alkylene. In some embodiments, A7 and A8 are each independently C1-C5 alkylene. In some embodiments, A7 and A8 are each independently C2-C4 alkylene. In some embodiments, A7 and A8 are C3 alkylene. In some embodiments, A7 or A8 is a bond. In some embodiments, A7 is a bond. In some embodiments, A8 is a bond.

[0324] In some embodiments, each R9 is independently C1-C 12 Alkyl, C5-C 16 Alkenyl, or C5-C 16 It is alkynyl. In some embodiments, each R9 is independently C3-C9 alkyl. In some embodiments, each R9 is independently a C5-C8 alkyl, such as a C6, C7, or C8 alkyl. In some embodiments, each R9 is independently C5-C 12 It is alkenyl. In some embodiments, each R9 is independently C5-C8 alkenyl, such as C6 alkenyl. In some embodiments, each R9 is independently C 10 C9-C such as alkynyl 11 It is alkynyl.

[0325] In some embodiments, each R 11 are independent, C1-C 12 It is alkyl. In some embodiments, each R 11 are independently C3-C9 alkyl. In some embodiments, each R 11 is independently a C5-C8 alkyl, such as a C6, C7, or C8 alkyl. In some embodiments, each R 11 independently, C5-C 12 It is alkenyl. In some embodiments, each R 11 is independently C5-C8 alkenyl, such as C6 alkenyl. In some embodiments, each R 11 independently, C 10 C9-C such as alkynyl 11 It is alkynyl.

[0326] In some embodiments, there is no dashed line connecting A1 and A2 and no dashed line connecting A1 and A3. In some embodiments, the dashed line connecting A1 and A2 is a bond, and there is no dashed line connecting A1 and A3. In some embodiments, the dashed line connecting A1 and A3 is a bond, and there is no dashed line connecting A1 and A2. In some embodiments, A1 and A2 are each independently C1-C5 alkyl or C1-C5 alkylene. In some embodiments, A1 and A2 are each independently C1-C3 alkyl. In some embodiments, A1 and A2 are each independently C1-C2 alkyl.

[0327] In some embodiments, A2 is C1-C3 alkyl, such as C1-C2 alkyl. In some embodiments, A3 is C1-C5 alkylene. In some embodiments, A3 is a C2-C4 alkylene, such as a C3 alkylene.

[0328] In some embodiments, there is no dashed line connecting A1 and A2 and no dashed line connecting A1 and A3, and A1 and A2 are each independently C1-C3 alkyl, such as C1-C2 alkyl. In some embodiments, there is no dashed line connecting A1 and A2 and no dashed line connecting A1 and A3, and A1 and / or A2 is unsubstituted C1-C5 alkyl, such as unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, or unsubstituted C1-C2 alkyl. In some embodiments, there is no dashed line connecting A1 and A2 and no dashed line connecting A1 and A3, and A1 and A2 are each independently unsubstituted C1-C5 alkyl, such as unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, or unsubstituted C1-C2 alkyl. In some embodiments, there is no dashed line connecting A1 and A2 and no dashed line connecting A1 and A3, and A1 and / or A2 is a substituted C1-C5 alkyl, such as a substituted C1-C4 alkyl, a substituted C1-C3 alkyl, or a substituted C1-C2 alkyl. In some embodiments, when the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, A1 and / or A2 is a C1-C5 alkylene.

[0329] In some embodiments, when the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing 4-, 5-, or 6-membered heterocycle. In some embodiments, when the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, A1 and / or A2 is unsubstituted C1-C5 alkylene. In some embodiments, when the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, A1 and A2 are each independently unsubstituted C1-C5 alkylene. In some embodiments, when the dashed line connecting A1 and A2 is a bond and there is no dashed line connecting A1 and A3, A1 and / or A2 is a substituted C1-C5 alkylene.

[0330] In some embodiments, when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A2 is C1-C3 alkyl and A1 and / or A3 is C1-C5 alkylene. In some embodiments, when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A1 and A3, together with the nitrogen atom to which they are both attached, form an N-containing 4-, 5-, or 6-membered heterocycle. In some embodiments, when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A1 is unsubstituted C1-C5 alkylene and A2 is unsubstituted C1-C5 alkyl (e.g., unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, unsubstituted C1-C2 alkyl). In some embodiments, when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A1 is unsubstituted C1-C5 alkylene and A2 is substituted C1-C5 alkyl (e.g., substituted C1-C4 alkyl, substituted C1-C3 alkyl, substituted C1-C2 alkyl). In some embodiments, when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A1 is substituted C1-C5 alkylene and A2 is unsubstituted C1-C5 alkyl (e.g., unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, unsubstituted C1-C2 alkyl). In some embodiments, when the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A1 is substituted C1-C5 alkylene and A2 is substituted C1-C5 alkyl (e.g., substituted C1-C4 alkyl, substituted C1-C3 alkyl, substituted C1-C2 alkyl).

[0331] In some embodiments, A1 or A2 is hydroxyl, -OR 12 , -C(=O)OR 12 , -OC(=O)R 12 or C1-C5 alkyl, C1-C2 alkyl, or C1-C5 alkylene, each R 12 are independent, C1-C 12 alkyl, for example, A1 or A2 is [ka] is.

[0332] In some embodiments, A1 and A2 are each independently: [ka] and the like, is a C1-C5 alkyl, a C1-C2 alkyl, or a C1-C5 alkylene substituted with a C1-C3 alkyl, such as

[0333] In some embodiments, A3 is unsubstituted C1-C5 alkylene. In some embodiments, A3 is unsubstituted C2-C4 alkylene. In some embodiments, A3 is unsubstituted C3 alkylene. In some embodiments, A3 is a substituted C1-C5 alkylene, such as a substituted C2-C4 alkylene, a substituted C3 alkylene, or the like. In some embodiments, A3 is one or two R 14 is a C3 alkylene substituted with R 14 is C1-C 12 Alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl, C1 alkyl).

[0334] In some embodiments, A3 is selected from two -R 14 is a C3 alkylene substituted with R 14 is C1-C 12 alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl, C1 alkyl). For example, A3 is [ka] is.

[0335] In some embodiments, [ka] has the following structure: [ka] wherein c is 1, 2, 3, 4, or 5.

[0336] In some embodiments, each R and / or each R11 -R 13 OC(=O)R 14 , -R 13 C(=O)OR 14 , or -R 13 OR 14 Substituted with, C1-C 12 alkyl (e.g., C3-C9 alkyl, C5-C8 alkyl, C6 alkyl), wherein R 14 is C1-C 12 Alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl, C1 alkyl). In some embodiments, R and R 11 -R 13 OC(=O)R 14 , -R 13 C(=O)OR 14 , or -R 13 OR 14 C2-C5 alkyl (e.g., C3-C4 alkyl) substituted with 14 is C1-C 12 alkyl (e.g., C1-C5 alkyl, C1-C3 alkyl, C1 alkyl). For example, R9 and R 11 teeth, [ka] is.

[0337] In some embodiments, the present disclosure provides compounds wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O), A4 is a bond, and A5 and A6 are each independently C3-C 10 alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is independently C3-C9 alkyl, and each R 11 are independently C3-C9 alkyl, there is no dashed line connecting A1 and A2 and there is no dashed line connecting A1 and A3, A1 and A2 are each independently C1-C3 alkyl, and A3 is C2-C4 alkylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0338] In some embodiments, the present disclosure provides a method for isolating a hydroxyl group wherein Z1 and Z2 are -C(=O)O-, A4 is a bond, and A5 and A6 are each independently C3-C 10 alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is independently C3-C9 alkyl, and each R 11 are independently C3-C9 alkyl, there is no dashed line connecting A1 and A2 and there is no dashed line connecting A1 and A3, A1 and A2 are each independently C1-C3 alkyl, and A3 is C2-C4 alkylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0339] In some embodiments, the present disclosure provides compounds wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-; A4 is a bond; A5 and A6 are each independently C3-C 10 alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is independently C3-C9 alkyl, and each R 11 are independently C3-C9 alkyl, the dashed line connecting A1 and A2 is a bond, there is no dashed line connecting A1 and A3, A1 and A2 are each independently C1-C5 alkylene, and A3 is C2-C4 alkylene, or a pharmaceutically acceptable salt or stereoisomer thereof.

[0340] In some embodiments, the present disclosure provides compounds wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-; A4 is a bond; A5 and A6 are each independently C3-C 10 alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is independently C3-C9 alkyl, and each R 11are independently C3-C9 alkyl, the dashed line connecting A1 and A2 is a bond, there is no dashed line connecting A1 and A3, A1 and A2 together with the nitrogen atom to which they are both attached form an N-containing 4-, 5-, or 6-membered heterocycle, and A3 is C2-C4 alkylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0341] In some embodiments, the present disclosure provides compounds wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-; A4 is a bond; A5 and A6 are each independently C3-C 10 alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is independently C3-C9 alkyl, and each R 11 are independently C3-C9 alkyl, the dashed line connecting A1 and A3 is a bond, there is no dashed line connecting A1 and A2, A2 is C1-C3 alkyl, and A1 and A3 are each independently C1-C5 alkylene, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0342] In some embodiments, the present disclosure provides compounds wherein Z1 and Z2 are each independently -C(=O)O- and -OC(=O)-; A4 is a bond; A5 and A6 are each independently C3-C 10 alkylene, A7 and A8 are each independently C2-C4 alkylene, each R9 is independently C3-C9 alkyl, and each R 11 are independently C3-C9 alkyl, the dashed line connecting A1 and A3 is a bond and there is no dashed line connecting A1 and A2, A2 is C1-C3 alkyl, and A1 and A3, together with the nitrogen atom to which they are both attached, form an N-containing 4-, 5-, or 6-membered heterocycle, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0343] In some embodiments, the amino lipid compound represented by Formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by Formula (II-VIb): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R1, and R2 are as defined in formula (II-I).

[0344] In some embodiments, A5 and A6 are each independently a C1, or a C2 hydrocarbylene or a bond. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 hydrocarbylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is a hydrocarbylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is a hydrocarbylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is a hydrocarbylene.

[0345] In some embodiments, A5 and A6 are each independently a C1 or C2 alkylene or a bond. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is alkylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is alkylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is alkylene.

[0346] In some embodiments, A5 and A6 are each independently C2 alkenylene or a bond. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkenylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is alkenylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C 13 , or C 14 It is alkenylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is alkenylene.

[0347] In some embodiments, A5 and A6 are each independently C2 alkynylene or a bond. In some embodiments, A5 and A6 are each independently C3, C4, C5, or C6 alkynylene. In some embodiments, A5 and A6 are each independently C7, C8, C9, or C 10 It is alkynylene. In some embodiments, A5 and A6 are each independently C 11 , C 12 , C13 , or C 14 It is alkynylene. In some embodiments, A5 and A6 are each independently C 15 , C 16 , C 17 , or C 18 It is alkynylene.

[0348] In some embodiments, the amino lipid compound represented by formula (II-VIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIb-a): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, and R2 are as defined in formula (II-VIb).

[0349] In some embodiments, the amino lipid compound represented by formula (II-VIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIb-b): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, Y1, R9, and R 11 is as defined in formula (II-VIb).

[0350] In some embodiments, the amino lipid compound represented by formula (II-VIb), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, has a structure represented by formula (II-VIb-c): [ka] During the ceremony, A1, A2, A3, A4, A5, A6, A7, A8, Z1, Z2, R9, and R 11is as defined in formula (II-VIb).

[0351] In some embodiments, the present disclosure provides a heterohydrocarbyl group represented by the above formula (II-I), (II-la), (II-lb), (II-Ic), (II-Id), (II-Ie), (II-II), (II-IIa), (II-IIb), wherein the hydrocarbyl, hydrocarbylene, alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, heterohydrocarbyl, or heterohydrocarbylene is optionally substituted with a hydroxyl, ester group, hydrocarbyloxy, hydrocarbyl, halogen, oxygen, sulfur, amino, or amido group. , (II-III), (II-IIIa), (II-IIIb), (II-IVa), (II-IVb), (II-Va), (II-Vb), (II-Vc), (II-Vd), (II-Ve), (II-Vf), (II-Vg), (II-Vh), (II-VIa), (II-VIa-a), (II-VIa-b), (II-VIa-c), (II-VIb), (II-VIb-a), (II-VIb-b), or (II-VIb-c), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0352] In some embodiments, the present disclosure provides an amino lipid compound having any of the structures shown in Table 1 below, including the above formula (II-I), (II-Ia), (II-Ib), (II-Ic), (II-Id), (II-Ie), (II-II), (II-IIa), (II-IIb), (II-III), (II-IIIa), (II-IIIb), (II-IVa), (II-IVb), (II-Va), (II-V The present invention provides an amino lipid compound represented by the formula: (II-VIa), (II-VIa-a), (II-VIa-b), (II-VIa-c), (II-VIb), (II-VIb-a), (II-VIb-b), or (II-VIb-c), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0353]

Table 1

[0354] All of the amino lipid compounds of the present disclosure possess hydrophobic properties due to the presence of long nonpolar residues, and at the same time, hydrophilic properties due to the amino group. Due to this amphiphilic property, the amino lipid compounds of the present disclosure can be used to form lipid nanoparticles such as lipid bilayers, micelles, and liposomes.

[0355] In the context of the present disclosure, the term "lipid nanoparticle" refers to a nanometer-sized material produced by introducing an amino lipid compound into an aqueous solution. The particle is in particular a lipid nanoparticle, a lipid bilayer vesicle (liposome), a multilamellar vesicle or a micelle.

[0356] In some embodiments, the lipid nanoparticles are liposomes comprising the amino lipid compounds of the present disclosure. Within the scope of this disclosure, liposomes are small microparticles consisting of a bilayer of lipid amphiphilic molecules encapsulating an aqueous compartment.

[0357] Liposome formation is not a spontaneous process. When lipids are introduced into water, lipid vesicles first form, which then form a bilayer or a series of bilayers, each separated by water molecules. Liposomes are formed by sonicating lipid vesicles in water.

[0358] In the context of this disclosure, the term "lipid bilayer" refers to a thin film formed by two layers of lipid molecules. The term "micelle" refers to an aggregate of surfactant molecules dispersed in a liquid colloid. Typical micelles in aqueous solution form aggregates upon contact with water, with the hydrophilic head region chelating the single hydrophobic tail region in the center of the micelle.

[0359] In one aspect, the present disclosure provides the use of an amino lipid compound of the present disclosure for the manufacture of a vehicle for an active ingredient, in some embodiments, the vehicle is in the form of a lipid nanoparticle, such as a lipid bilayer, a micelle, or a liposome.

[0360] Lipid nanoparticles (LNPs) In another aspect, the present disclosure provides lipid nanoparticles comprising the amino lipid compounds of the present disclosure. In some embodiments, the lipid nanoparticles further comprise one or more of a helper lipid, a structural lipid, and a PEG-lipid (polyethylene glycol-lipid). In some further embodiments, the lipid nanoparticle further comprises a helper lipid, a structural lipid, and a PEG lipid.

[0361] In some embodiments, the lipid nanoparticles comprise an amino lipid compound in an amount of about 25.0% to 75.0%, e.g., about 25.0%-28.0%, 28.0%-32.0%, 32.0%-35.0%, 35.0%-40.0%, 40.0%-42.0%, 42.0%-45.0%, 45.0%-46.3%, 46.3%-48.0%, 48.0%-49.5%, 49.5%-50.0%, 50.0%-55.0%, 55.0%-60.0%, 60.0%-65.0%, or 65.0%-75.0%, based on the total amount of amino lipid compound, helper lipid, structural lipid, and PEG-lipid.

[0362] In some embodiments, the lipid nanoparticles comprise helper lipids in an amount of about 5.0% to 45.0%, e.g., about 5.0%-9.0%, 9.0%-9.4%, 9.4%-10.0%, 10.0%-10.5%, 10.5%-11.0%, 11.0%-15.0%, 15.0%-16.0%, 16.0%-18.0%, 18.0%-20.0%, 20.0%-25.0%, 25.0%-33.5%, 33.5%-37.0%, 37.0%-40.0%, 40.0%-42.0%, or 42.0%-45.0%, based on the total amount of amino lipid compound, helper lipid, structural lipid, and PEG-lipid.

[0363] In some embodiments, the lipid nanoparticles comprise from about 0.0% to 50.0%, e.g., about 0.0%-10.0%, 10.0%-15.5%, 15.5%-18.5%, 18.5%-22.5%, 22.5%-23.5%, 23.5%-28.5%, 28.5%-33.5%, 33.5%-35.0%, 35.0%-36.5%, 36.5%-37.5%, 38.5%-40.5%, 40.5%-41.5%, 41.5%-42.5%, 42.5%-43.5%, 43.5%-44.5%, 44.5%-45.5%, 45.5%-46.5%, 46.5%-47.5%, 47.5%-48.5%, 48.5%-49.5%, 49.5%-50.5%, 50.5%-51.5%, 51.5%-52.5%, 52.5%-53.5%, 53.5%-54.5%, 54.5%-55.5%, 55.5%-56.5%, 56.5%-57.5%, 57.5%-58.5%, 58.5%-59.5%, 59.5%-60.5%, 60.5%-61.5%, 61.5%-62.5%, 62.5%-63.5%, 63.5%-64.5%, 64.5%-65.5%, 65.5%-66.5%, 66.5%-67.5%, 67.5%-68.5%, 68.5%-69.5%, containing structural lipids in amounts (mol percent) of 5%-38.0%, 38.0%-38.5%, 38.5%-39.0%, 39.0%-39.5%, 39.5%-40.5%, 40.5%-41.5%, 41.5%-42.5%, 42.5%-42.7%, 42.7%-43.0%, 43.0%-43.5%, 43.5%-45.0%, 45.0%-46.5%, 46.5%-48.5%, or 46.5%-50.0%.

[0364] In some embodiments, the lipid nanoparticles comprise PEG-lipids in an amount (mol percent) of about 0.5% to 5.0%, e.g., about 0.5%-1.0%, 1.0%-1.5%, 1.5%-1.6%, 1.6%-2.0%, 2.0%-2.5%, 2.5%-3.0%, 3.0%-3.5%, 3.5%-4.0%, 4.0%-4.5%, or 4.5%-5.0%, based on the total amount of amino lipid compound, helper lipid, structural lipid, and PEG-lipid.

[0365] In some embodiments described above, the helper lipid is a phospholipid. Phospholipids are generally semi-synthetic and may be naturally derived or chemically modified. Examples of phospholipids include DSPC (distearoylphosphatidylcholine), DOPE (dioleoylphosphatidylethanolamine), DOPC (dioleoyllecithin), DOPS (dioleoylphosphatidylserine), DSPG (1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol)), DPPG (dipalmitoylphosphatidylglycerol), DPPC (dipalmitoylphosphatidylcholine), DGTS (1,2-dipalmitoyl-sn-glycero-3-O-4'-(N,N,N-trimethyl)homoserine), lysophospholipids, and the like. Preferably, the helper lipid is one or more selected from the group consisting of DSPC, DOPE, DOPC, and DOPS. In some embodiments, the helper lipid is DSPC and / or DOPE.

[0366] In some embodiments, the structured lipid is a sterol, including but not limited to cholesterol, cholesterol esters, steroid hormones, steroid vitamins, bile acids, cholesterin, ergosterol, β-sitosterol, oxidized cholesterol derivatives, etc. Preferably, the structured lipid is at least one selected from cholesterol, cholesteryl esters, steroid hormones, steroid vitamins, and bile acids. In some embodiments, the structured lipid is cholesterol, preferably high-purity cholesterol, particularly injectable-grade high-purity cholesterol such as CHO-HP (manufactured by AVT).

[0367] As used herein, the term PEG-lipid (polyethylene glycol-lipid) refers to a conjugate of polyethylene glycol with a lipid structure. Preferably, the PEG-lipid is selected from PEG-DMG and PEG-distearoylphosphatidylethanolamine (PEG-DSPE), preferably PEG-DMG. Preferably, the PEG-DMG is a polyethylene glycol (PEG) derivative of 1,2-dimyristoyl-sn-glycerol. Preferably, the PEG has an average molecular weight of about 2,000 to 5,000, preferably about 2,000.

[0368] In some embodiments described above, the lipid nanoparticles have a molar ratio of amino lipid compound of the present disclosure:helper lipid:structural lipid:PEG-lipid of about 45:10:42.5:2.5, or 45:11:41.5:2.5, or 42.0:10.5:45.0:2.5, or 42.0:16.0:39.5:2.5, or 40.0:16.0:41.5:2.5, or 40.0:18.0:3 9.5:2.5, or 35.0:16.0:46.5:2.5, or 35.0:25.0:36.5:3.5, or 28.0:33.5:35.0:3.5, or 32.0:37.0:40.5:0.5, or 35.0:40.0:22.5:2.5, or 40.0:42.0:15.5:2.5, or 40.0:20.0:38.5:1.5, or 45.0:15.0:38. 5:1.5, or 55.0:5.0:38.5:1.5, or 60.0:5.0:33.5:1.5, or 45.0:20.0:33.5:1.5, or 50.0:20.0:28.5:1.5, or 55.0:20.0:23.5:1.5, or 60.0:20.0:18.5:1.5, or 40.0:15.0:43.5:1.5, or 50.0:15.0:33.5:1. 5, or 55.0:15.0:28.5:1.5, or 60.0:15.0:23.5:1.5, or 40.0:10.0:48.5:1.5, or 45.0:10.0:43.5:1.5, or 55.0:10.0:33.5:1.5, or 40.0:5.0:53.5:1.5, or 45.0:5.0:48.5:1.5, or 50.0:5.0:43.5:1.5. In some such embodiments, the helper lipid is DOPE and the structural lipid is CHO-HP.

[0369] In other embodiments described above, the lipid nanoparticles may have a molar ratio of amino lipid compound of the present disclosure:helper lipid:structural lipid:PEG-lipid of about 50.0:10.0:38.5:1.5, or 50.0:9.0:38.0:3.0, or 49.5:10.0:39.0:1.5, or 48.0:10.0:40.5:1.5, or 46.3:9.4:42.7:1.6, or 45.0:9.0 :43.0:3.0, or 45.0:11.0:41.5:2.5, or 42.0:10.5:45.0:2.5, or 42.0:16.0:39.5:2.5, or 40.0:16.0:41.5:2.5, or 40.0:18.0:39.5:2.5, or 35.0:40.0:22.5:2.5, or 40.0:20.0:38.5:1.5, or 45.0:15.0:38 .5:1.5, or 55.0:5.0:38.5:1.5, or 60.0:5.0:33.5:1.5, or 45.0:20.0:33.5:1.5, or 50.0:20.0:28.5:1.5, or 55.0:20.0:23.5:1.5, or 60.0:20.0:18.5:1.5, or 40.0:15.0:43.5:1.5, or 50.0:15.0:33.5:1 0.5, or 55.0:15.0:28.5:1.5, or 60.0:15.0:23.5:1.5, or 40.0:10.0:48.5:1.5, or 45.0:10.0:43.5:1.5, or 55.0:10.0:33.5:1.5, or 40.0:5.0:53.5:1.5, or 45.0:5.0:48.5:1.5, or 50.0:5.0:43.5:1.5. In some such embodiments, the helper lipid is DSPC and the structural lipid is CHO-HP.

[0370] In some embodiments, the lipid nanoparticles have the amino lipid compounds, helper lipids, structural lipids, and PEG-lipids of the present disclosure in mole percent (%) based on the total amount of amino lipid compounds, helper lipids, structural lipids, and PEG-lipids as shown in Table 2, Nos. 1-24, below:

[0371] [Table 2]

[0372] In some embodiments, the lipid nanoparticles have the amino lipid compounds, helper lipids, structural lipids, and PEG-lipids of the present disclosure in mole percent (%) as shown in Table 3, Nos. 25-42, below, based on the total amount of amino lipid compounds, helper lipids, structural lipids, and PEG-lipids:

[0373] [Table 3]

[0374] As mentioned above, the lipid nanoparticles of the present disclosure can be used for delivering active ingredients. In some embodiments, the active ingredient comprises a therapeutic and / or prophylactic agent. The term "therapeutic agent" or "prophylactic agent" refers to any agent that has a therapeutic, diagnostic, and / or prophylactic effect and / or induces a desired biological and / or pharmacological effect when administered to a subject.

[0375] An "effective amount" or a "therapeutically effective amount" refers to an amount of a compound of the present invention or a lipid nanoparticle comprising a compound of the present invention that, when administered to a mammal (preferably a human), is sufficient to effectively treat the mammal (preferably a human). The amount of lipid nanoparticles of the present invention that constitutes a "therapeutically effective amount" depends on the compound, the condition and its severity, the mode of administration, and the age of the mammal being treated, but can be routinely determined by one skilled in the art in light of their own knowledge and this disclosure.

[0376] Preferably, the pharmaceutically active ingredient is a biologically active ingredient, which is a substance that has a biological effect when introduced into a cell or host, for example, by stimulating an immune or inflammatory response, by exerting enzymatic activity, by complementing a mutation, etc. Biologically active ingredients include, but are not limited to, nucleic acids, proteins, peptides, antibodies, small molecules, and mixtures thereof. Preferably, the biologically active moiety is a nucleic acid.

[0377] In some embodiments, the biologically active ingredient is an anti-neoplastic agent, an antibiotic, an immunomodulatory agent, an anti-inflammatory agent, an agent acting on the central nervous system, a polypeptide, a polypeptoid, or a mixture thereof.

[0378] Lipid nanoparticles that encapsulate an active ingredient in their internal aqueous space are sometimes called "lipid nanoparticle drugs."

[0379] In the context of this disclosure, the term "cell" is a generic term and includes individual cells, tissues, organs, insect cells, avian cells, fish cells, amphibian cells, mammalian cells, primary cells, continuous cell lines, stem cells, and / or cultures of genetically engineered cells (e.g., recombinant cells expressing heterologous polypeptides or proteins, such as growth factors or blood factors).

[0380] In some embodiments described above, the lipid nanoparticles of the present disclosure further comprise a nucleic acid. In some embodiments, the mass ratio of amino lipid compounds of the present disclosure to nucleic acid in the lipid nanoparticle is about (5-30):1, e.g., about (5-10):1, (10-15):1, (15-20):1, (20-25):1, or (25-30):1, preferably about 10:1.

[0381] In some embodiments, the nucleic acid is selected from the group consisting of RNA, antisense oligonucleotides, and DNA. In some embodiments, the RNA is selected from the group consisting of messenger RNA (mRNA), ribosomal RNA (rRNA), microRNA (miRNA), transfer RNA (tRNA), short interfering RNA (siRNA), small nuclear RNA (snRNA), short hairpin RNA (shRNA), single guide RNA (sgRNA), Cas9 mRNA, or a mixture thereof. In some embodiments, messenger RNA (mRNA) encodes a polypeptide and / or protein of interest, including any naturally occurring or non-naturally occurring or otherwise modified polypeptide. In some embodiments, the polypeptide and / or protein encoded by the mRNA may have a therapeutic and / or prophylactic effect when expressed in a cell.

[0382] In some embodiments, RNA is siRNA, which can selectively reduce the expression of target gene or down-regulate the expression of gene.For example, siRNA can be selected so that the gene associated with specific disease, disorder or symptom is silenced when lipid nanoparticles containing siRNA are administered to a subject in need thereof.The siRNA can comprise the sequence complementary to the mRNA sequence that codes for target gene or protein.In some embodiments, the siRNA can be immunomodulatory siRNA.

[0383] In certain embodiments, RNA is sgRNA and / or cas9 mRNA.sgRNA and / or cas9 mRNA can be used as gene editing tools.For example, sgRNA-cas9 complex can affect the mRNA translation of cellular gene. In some embodiments, RNA is shRNA or its encoding vector or plasmid.shRNA can be produced in target cell after appropriate construct is delivered into nucleus.The construct and mechanism related to shRNA are well known in the relevant technical field. In some embodiments, the DNA is a plasmid. In some embodiments, lipid nanoparticles are used to deliver nucleic acids. In some embodiments, lipid nanoparticles can be used for, for example, gene therapy, gene vaccination, protein replacement therapy, antisense therapy, or interfering RNA therapy.

[0384] Pharmaceutical Composition In another aspect, the present invention provides a pharmaceutical composition comprising a lipid nanoparticle as described above and a pharmaceutically acceptable carrier, diluent, or excipient.

[0385] In some embodiments, the pharmaceutical composition further comprises a buffer. In some such embodiments, the buffer is selected from phosphate buffer and Tris buffer, preferably phosphate buffer. In some embodiments, the buffer has a concentration of about 5 mmol / L to about 30 mmol / L, preferably about 10 mmol / L. In some embodiments, the buffer has a pH of about 6 to 8, preferably about 7 to 8, more preferably about 7 to 7.5.

[0386] In some embodiments, the pharmaceutical composition further comprises a cryoprotectant. In some such embodiments, the cryoprotectant is selected from sucrose and trehalose, preferably sucrose. In some embodiments, the cryoprotectant has a concentration of about 50 mg / ml to 100 mg / ml.

[0387] In some embodiments described above, the pharmaceutical composition further comprises a cryoprotectant. In some such embodiments, the cryoprotectant is selected from sucrose and trehalose, preferably sucrose. In some embodiments, the cryoprotectant has a concentration of about 50 mg / ml to 100 mg / ml.

[0388] Purpose The lipid nanoparticles of the present disclosure have excellent properties for encapsulating biologically active ingredients. Lipid nanoparticles containing biologically active ingredients can be used to deliver any of a variety of therapeutic agents into cells. The present disclosure includes the use of such lipid nanoparticles for delivering biologically active ingredients into cells. The present invention also provides a method for delivering biologically active ingredients to cells, tissues, or organs, comprising contacting lipid nanoparticles of the present disclosure containing biologically active ingredients with cells, tissues, or organs. This provides new therapeutic possibilities for subjects.

[0389] In some embodiments, the tissue or organ is selected from the group consisting of spleen, liver, kidney, lung, femur, ocular tissue, vascular endothelium, lymphatic, and tumor tissue.

[0390] Preferably, the cell is a mammalian cell; more preferably, the mammalian cell is in a mammal. As used herein, the subject may be any mammal, and is preferably selected from the group consisting of mice, rats, pigs, cats, dogs, horses, goats, cows, monkeys, etc. In some preferred embodiments, the subject is a human.

[0391] The present disclosure provides a method for producing a polypeptide and / or protein of interest in mammalian cells, comprising contacting the cells with lipid nanoparticles containing mRNA encoding the polypeptide and / or protein of interest, wherein contacting the cells with the lipid nanoparticles allows the mRNA to be taken up intracellularly and translated to produce the polypeptide and / or protein of interest.

[0392] In yet another aspect, the present disclosure provides the use of the amino lipid compound, lipid nanoparticle or pharmaceutical composition of the present disclosure in the manufacture of a medicament.Preferably, the medicament is a nucleic acid drug.Preferably, the pharmaceutical composition is used for the treatment and / or prevention of disease. In some embodiments, the disease is selected from the group consisting of a rare disease, an infectious disease, a cancer, a genetic disease, an autoimmune disease, diabetes, a neurodegenerative disease, a cardiovascular disease, a renal vascular disease, and a metabolic disease. The pharmaceuticals are used, for example, in gene therapy, protein replacement therapy, antisense therapy, or therapy with interfering RNA, genetic vaccination, and the like. In some embodiments, the cancer is selected from one or more of lung cancer, stomach cancer, liver cancer, esophageal cancer, colon cancer, pancreatic cancer, brain cancer, lymphoma, blood cancer, or prostate cancer. In some embodiments, the genetic disease is selected from one or more of hemophilia, thalassemia, and Gaucher disease. In some embodiments, genetic vaccination is preferably used to treat and / or prevent cancer, allergies, toxicity, and pathogen infection. In some embodiments, the pathogen is selected from one or more of a virus, a bacterium, or a fungus.

[0393] The present disclosure provides a method of treating a disease or disorder in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of lipid nanoparticles as described above. Preferably, the disease or disorder is selected from the group consisting of a rare disease, an infectious disease, a cancer, a genetic disease, an autoimmune disease, diabetes, a neurodegenerative disease, a cardiovascular disease, a renal vascular disease, and a metabolic disease.

[0394] In yet another aspect, the present disclosure provides the use of the amino lipid compound, lipid nanoparticle, or pharmaceutical composition of the present disclosure in the manufacture of a medicament for nucleic acid transfer.In some embodiments, the nucleic acid is selected from the group consisting of RNA, antisense oligonucleotide, and DNA.In some embodiments, the RNA is selected from the group consisting of messenger RNA (mRNA), ribosomal RNA (rRNA), microRNA (miRNA), transfer RNA (tRNA), short interfering RNA (siRNA), small nuclear RNA (snRNA), short hairpin RNA (shRNA), single guide RNA (sgRNA), Cas9 mRNA, or a mixture thereof.In some embodiments, the DNA is a plasmid.

[0395] Preparation method In yet another embodiment, the present disclosure also provides a general synthetic process for preparing the amino lipid compounds of formula (Id) or (Ie) of the present disclosure, as follows: [ka]

[0396] [ka]

[0397] or [ka]

[0398] In yet another aspect, the present disclosure further provides a general synthetic process for synthesizing the amino lipid compounds of formula (II-I) of the present disclosure as follows: (1) When X is C, Y1 is -Z3C(=O)Z4-, and Z3 and Z4 are not both bonds, and A 12 is a bond, [ka]

[0399] [ka]

[0400] or (2) When X is C, Y1 is -N(R5); [ka]

[0401] or (3) When X is C, Y is -ZC(=O)Z, Z is a bond, and Z is not a bond; [ka]

[0402] or (4) When X is C, Y is -ZC(=O)Z, Z is not a bond, and Z is a bond; [ka]

[0403] or (5) When X is N, Y is —ZC(═O)Z—, Z is a bond, and A 12 is a bond, [ka]

[0404] or (6) When X is N, Y1 is -Z3C(=O)Z4-, Z4 is a bond, and A 12 is not a bond. [ka]

[0405] In yet another embodiment, the lipid nanoparticles or pharmaceutical compositions of the present disclosure can be prepared according to methods known in the art. For example, the method may include the following steps: (1) Formulation: Formulating a suitable aqueous phase; and formulating an organic phase containing an amino lipid compound of the present disclosure, and optionally a helper lipid, a structural lipid, and / or a PEG lipid; (2) Encapsulation: Mixing an appropriate amount of the aqueous phase with the organic phase; (3) Dialysis: Optionally, dialyzing the mixture of step (2); and (4) Sterilization: Optionally, the product of step (3) is sterilized by a sterilizing filter, such as a 0.22 μm microporous membrane.

[0406] In some embodiments, lipid nanoparticles or pharmaceutical compositions of the present disclosure comprising nucleic acids, particularly mRNA, can be prepared by a method comprising the following steps: (1) Formulation: Formulating an aqueous phase containing nucleic acids; and formulating an organic phase (e.g., an ethanol phase) containing an amino lipid compound of the present disclosure, and optionally a helper lipid, a structural lipid, and / or a PEG lipid; (2) Encapsulation: Mixing an appropriate amount of the aqueous phase with the organic phase; (3) Dialysis: Optionally, dialyze the mixture of step (2); (4) Sterilization: Optionally, the product of step (3) is sterilized by a sterilizing filter, such as a 0.22 μm microporous membrane.

[0407] Beneficial effects The amino lipid compounds of the present disclosure can form vehicles such as lipid nanoparticles that have excellent properties for encapsulating biologically active ingredients and can be used to deliver biologically active ingredients, particularly water-insoluble drugs or active ingredients (such as nucleic acids) that are prone to degradation or decomposition, and can improve their bioavailability and efficacy, immune activity, transfection efficiency (for nucleic acids), safety, tissue and / or cell targeting or specificity, or preference for particular organs and / or tissues. [Example]

[0408] In order to make the objectives, technical solutions and advantages of the present disclosure clearer, the present disclosure will be described below with reference to specific examples. The following examples are merely illustrative of the present disclosure and are not intended to be limiting.

[0409] Example The following examples are offered by way of illustration and not by way of limitation. Experimental methods for which specific conditions are not specified in the examples are generally under conventional conditions or those recommended by the raw material or commercial product manufacturers, and reagents of unspecified origin are generally conventional reagents that are commercially available. The abbreviations used in the examples have the following meanings: Pd / C palladium / carbon; EA ethyl acetate; DCM dichloromethane; TEA triethylamine; MPa megapascal; DMF N,N-dimethylformamide; EDCI 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; DMAP 4-dimethylaminopyridine; TBAF tetrabutylammonium fluoride; TEMPO 2,2,6,6-tetramethylpiperidinoxy; NaDCC Sodium dichloroisocyanurate TBSCl tert-butyldimethylsilyl chloride h time; min minutes.

[0410] Example 1: Synthesis of amino lipid compound 383 [ka] [ka]

[0411] Step 1: Synthesis of DFSGN-T Reaction scheme: [ka]

[0412] Testing Procedure: EDCI (4.43 g, 23.13 mmol), DCM (26 mL), and TEA (2.34 g, 23.13 mmol) were sequentially added to a 100 mL round-bottom flask and stirred vigorously for 5 minutes. Then, DMAP (0.47 g, 3.86 mmol), BHB (4,4-bis(heptyloxy)butanol) (4.2 g, 13.88 mmol), and DTN (10-oxononadecanedioic acid) (2.64 g, 7.71 mmol) were added and stirred at room temperature overnight. After the reaction was complete, DCM (100 mL) and water (150 mL) were added and stirred, followed by extraction and separation. The organic phase was collected, washed with 50 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 7.7 g of crude DFSGN-T. This was purified by silica gel column chromatography and eluted with ethyl acetate:n-heptane=1.5:1 to obtain 5.13 g of DFSGN-T in a yield of 81%.

[0413] Step 2: Synthesis of DFSGN-C [ka]

[0414] Testing Procedure: DFSGN-T (5.13 g, 5.62 mmol) was placed in a 250 mL single-neck flask, dissolved in methanol (50 mL), and cooled to 0 °C. Sodium borohydride (0.23 g, 6.18 mmol) was added portionwise with stirring, and the reaction was maintained for 1 h after the addition was complete. After the reaction was complete, the solvent was removed under reduced pressure, and water (100 mL) and DCM (100 mL) were added and stirred, followed by extraction and separation. The organic phase was collected, washed with water (50 mL), and concentrated under reduced pressure at 45 °C to give 5.2 g of crude DFSGN-C. This was purified by silica gel column chromatography eluting with ethyl acetate:n-heptane = 1.5:1 to give 4.5 g of DFSGN-C in 88% yield.

[0415] Step 3: Synthesis of 383-D Reaction scheme: [ka]

[0416] Testing Procedure: DFSGN-C (1.8 g, 1.97 mmol), DCM (18 mL), DMAP (72 mg, 0.60 mmol), and pyridine (0.39 g, 4.93 mmol) were added to a 50 mL single-neck round-bottom flask and stirred at room temperature. p-Nitrophenyl chloroformate (0.79 g, 3.94 mmol) was added portionwise and stirred for an additional 1 h. After the reaction was complete, the mixture was diluted with water (150 mL) and extracted with DCM (100 mL). The organic phase was collected, washed with water (80 mL), and then concentrated under reduced pressure to give 3.0 g of crude 383-D. This was purified by silica gel column chromatography eluting with ethyl acetate:n-heptane = 1.5:1 to give 1.74 g of 383-D in 82% yield.

[0417] Step 4: Synthesis of amino lipid compound 383 Reaction scheme: [ka]

[0418] Testing Procedure: 383-D (1.74 g, 1.61 mmol), DCM (18 mL), DMAP (59 mg, 0.48 mmol), triethylamine (0.49 mg, 4.84 mmol), and diethylaminopropanol (1.27 g, 9.68 mmol) were added to a 50 mL single-neck round-bottom flask and stirred at room temperature for 2 days. After the reaction was complete, the mixture was diluted with water (100 mL) and extracted with DCM (100 mL). The organic phase was collected, washed with water (80 mL), and then concentrated under reduced pressure to give 2.8 g of crude amino lipid compound 383. This was purified by silica gel column chromatography eluting with ethyl acetate:n-heptane = 1.5:1 to give 945 mg of amino lipid compound 383 in 55% yield and 96.55% purity.

[0419] Aminolipid Compounds 383 [ka] 1 H NMR in CDCl3 δ 4.69-4.65 (m, 1H), 4.48 (t, J= 5.3 Hz, 2H), 4.17 (t, J= 6.6 Hz, 2H), 4.07 (t, J= 6.1 Hz, 4H), 3.58-3.54 (m, 4H), 3.42-3.38 (m, 4H), 2.53-2.49 (m, 6H), 2.28 (t, J= 7.5 Hz, 4H), 1.83-1.79 (m, 2H), 1.71-1.66 (m, 12H), 1.61-1.52 (m, 12H), 1.36-1.28 (m, 52H), 1.01 (t, J= 7.2 Hz, 6H) 0.88 (t, J= 7.1 Hz, 12H). LC-MS (ESI): (M+H) calculated 1070.92, found 1071.5.

[0420] Example 2: Synthesis of amino lipid compound 382 Following the general synthesis process, amino lipid compound 382 was prepared according to the method of Example 1, substituting compound BSB for BHB, to obtain 655 mg of amino lipid compound 382 in 58% yield and 97.63% purity. BSB [ka]

[0421] Aminolipid Compounds 382 [ka] 1 H NMR in CDCl3 δ4.69-4.65 (m, 1H), 4.48 (t, J= 5.1 Hz, 2H), 4.17 (t, J= 6.5 Hz, 2H), 4.07 (t, J= 6.0 Hz, 4H), 3.58-3.55 (m, 4H), 3.42-3.38 (m, 4H), 2.53-2.49 (m, 6H), 2.28 (t, J= 7.6 Hz, 4H), 1.84-1.79 (m, 2H), 1.74-1.65 (m, 12H), 1.61-1.52 (m, 12H), 1.37-1.27 (m, 44H), 1.01 (t, J= 7.2 Hz, 6H) 0.89 (t, J= 6.9 Hz, 12H). LC-MS (ESI): (M+H) calculated 1014.85, found 1015.4.

[0422] Example 3: Synthesis of amino lipid compound 1245 Step 1: Synthesis of 3-bromopropanal Reaction scheme: [ka]

[0423] Testing Procedure: 3-Bromopropanol (10.0 g, 72 mmol) and DCM (150 mL) were added to a 500 mL single-neck flask. TEMPO (225 mg, 1.44 mmol), potassium bicarbonate (5.05 g, 50.4 mmol), and sodium bromide (296 mg, 2.88 mmol) were added with stirring. The reaction solution was cooled to 5 °C, and aqueous NaDCC (9.5 g, 43.2 mmol) was added dropwise. After the dropwise addition was complete, the mixture was reacted at 5 °C for 3 h and then filtered. The filter cake was washed once with 20 mL of water and once with 20 mL of DCM. The organic phase was collected and concentrated under reduced pressure to give crude 3-bromopropanal. This was purified by silica gel column chromatography eluting with DCM to give 9.0 g of 3-bromopropanal in 91.2% yield.

[0424] Step 2: Synthesis of 3,3-dioctyloxybromopropane Reaction scheme: [ka]

[0425] Testing Procedure: 3-Bromopropanal (9.0 g, 65.7 mmol), cyclopentyl methyl ether (80 mL), 1-octanol (21.4 g, 164.3 mmol), and ammonium bromide (322 mg, 3.3 mmol) were added to a 250 mL single-neck flask. The reaction solution was heated to 130 °C with stirring and refluxed to separate water. The reaction was allowed to proceed for 6 hours and then filtered. The filtrate was collected and concentrated under reduced pressure to obtain crude 3,3-dioctyloxybromopropane. This was purified by silica gel column chromatography eluting with n-hexane, yielding 9.63 g of 3,3-dioctyloxybromopropane in 38.6% yield.

[0426] Step 3: Synthesis of 1245-A Reaction scheme: [ka]

[0427] Testing Procedure: 2-Hydroxymethyl-1,3-propanediol (4.5 g, 42.7 mmol) and DMF (250 mL) were added to a 500 mL two-neck flask. The reaction mixture was cooled to 0 °C with stirring, and sodium hydride (1.5 g, 37.0 mmol) was added portionwise. The mixture was allowed to react at 0 °C for 1 h. A DMF solution of 3,3-dioctyloxy-1-bromopropane (11.2 g, 29.5 mmol, dissolved in 20 mL of DMF) was then added dropwise. After the dropwise addition was complete, the reaction mixture was warmed to 10 °C for 6 h, quenched by the addition of 200 mL of water, transferred to a 1 L separatory funnel, added 300 mL of water, and extracted twice with 200 mL of ethyl acetate. The combined organic phases were washed with 300 mL of water and then concentrated under reduced pressure to give crude 1245-A. This was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate=3:1 to obtain 5.87 g of 1245-A in a yield of 49.2%.

[0428] Step 4: Synthesis of 1245-B Reaction scheme: [ka]

[0429] Testing Procedure: 1245-A (5.87 g, 14.0 mmol) and DCM (280 mL) were added to a 500 mL two-neck flask. The reaction solution was cooled to -10 °C with stirring, and linoleic acid (4.32 g, 15.4 mmol), EDCI (4.03 g, 21.0 mmol), DMAP (171 mg, 1.4 mmol), and pyridine (1.66 g, 21.0 mmol) were added. After the dropwise addition was completed, the mixture was reacted at -10 °C for 8 h. The reaction solution was warmed to room temperature and quenched by adding 200 mL of water, followed by two extractions with 200 mL of DCM. The combined organic phases were concentrated under reduced pressure to give crude 1245-B. This was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 5:1 to give 5.6 g of 1245-B in 58.7% yield.

[0430] Step 5: Synthesis of amino lipid compound 1245 Reaction scheme: [ka]

[0431] Testing Procedure: 1245-B (4.85 g, 7.12 mmol), DCM (70 mL), DMAP (261 mg, 2.14 mmol), and pyridine (1.41 g, 17.8 mmol) were added to a 250 mL two-neck flask and stirred at room temperature. Next, p-nitrophenyl chloroformate (2.87 g, 15.54 mmol) was slowly added in small portions and allowed to react at room temperature for 1 hour. 3-Diethylamino-1-propanol (2.8 g, 21.4 mmol) was added and allowed to react at room temperature for 12 hours. The solvent was removed under reduced pressure, and 100 mL of water was added. The mixture was extracted twice with 100 mL of n-hexane. The combined organic phases were washed with 150 mL of water and then concentrated under reduced pressure to obtain crude amino lipid compound 1245. This was purified by silica gel column chromatography and eluted with n-hexane:ethyl acetate=1:1 to obtain 3.28 g of amino lipid compound 1245 in a yield of 55.0% and a purity of 96.30%. LC-MS (ESI): (M+H) calculated 838.7, found 839.1.

[0432] Example 4: Synthesis of amino lipid compound 1246 Step 1: Synthesis of 4-(tert-butyldimethylsilyl)oxo-1-butanol Reaction scheme: [ka]

[0433] Testing Procedure: 1,4-Butanediol (20.0 g, 222 mmol), DCM (660 mL), and imidazole (22.67 g, 333 mmol) were added to a 1 L single-neck flask. The reaction solution was cooled to 0 °C with stirring, and TBSCl (36.7 g, 244 mmol) was added. The mixture was allowed to react at 0 °C for 6 h. 400 mL of water was added and the mixture was extracted twice with 300 mL of DCM. The combined organic phase was concentrated under reduced pressure to give crude 4-(tert-butyldimethylsilyl)oxo-1-butanol. This crude product was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 5:1 to give 22.5 g of 4-(tert-butyldimethylsilyl)oxo-1-butanol in 49.5% yield.

[0434] Step 2: Synthesis of 4-(tert-butyldimethylsilyl)oxo-1-butanal Reaction scheme: [ka]

[0435] Testing Procedure: 4-(tert-Butyldimethylsilyl)oxo-1-butanol (22.5 g, 110 mmol) and DCM (300 mL) were added to a 1 L single-neck flask, and TEMPO (344 mg, 2.2 mmol), potassium bicarbonate (7.7 g, 77 mmol), and sodium bromide (453 mg, 4.4 mmol) were added with stirring. The reaction solution was cooled to 5 °C, and aqueous NaDCC (14.5 g, 66 mmol, dissolved in 150 mL of water) was added dropwise. The reaction mixture was allowed to react at 5 °C for 3 h and then filtered. The filter cake was washed once with 50 mL of water and once with 50 mL of DCM. The filtrate was collected and the phases were separated. The organic phase was collected, and the aqueous phase was extracted twice with 150 mL of DCM. The combined organic phases were concentrated under reduced pressure to give crude 4-(tert-butyldimethylsilyl)oxo-1-butanal. This was purified by silica gel column chromatography eluting with DCM to give 11.4 g of 4-(tert-butyldimethylsilyl)oxo-1-butanal in a yield of 51.2%.

[0436] Step 3: Synthesis of 4,4-dioctyloxy-1-TBS butanol Reaction scheme: [ka]

[0437] Testing Procedure: 4-(tert-Butyldimethylsilyl)oxo-1-butanal (10.0 g, 49.4 mmol), cyclopentyl methyl ether (80 mL), 1-octanol (16.1 g, 123.5 mmol), and ammonium bromide (242 mg, 2.47 mmol) were added to a 250 mL single-neck flask. The reaction solution was heated to 130 °C with stirring and refluxed to separate water. The reaction was allowed to proceed for 6 hours and then filtered. The filtrate was collected and concentrated under reduced pressure to obtain crude 4,4-dioctyloxy-1-TBS butanol. This was purified by silica gel column chromatography eluting with n-hexane, yielding 10.2 g of 4,4-dioctyloxy-1-TBS butanol in 46.4% yield.

[0438] Step 4: Synthesis of dioctyloxy-1-butanol Reaction scheme: [ka]

[0439] Testing Procedure: 4,4-Dioctyloxy-1-butanol (10.0 g, 22.5 mmol), tetrahydrofuran (110 mL), and TBAF (10.6 g, 33.7 mmol) were added to a 250 mL single-neck flask and allowed to react with stirring at room temperature for 6 hours. After this, 80 mL of saturated sodium bicarbonate solution was added and the mixture was extracted twice with 80 mL of ethyl acetate. The combined organic phases were washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and filtered. The filtrate was collected and concentrated under reduced pressure to obtain crude 4,4-dioctyloxy-1-butanol. This crude product was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 5:1 to obtain 6.5 g of 4,4-dioctyloxy-1-butanol in 87.4% yield.

[0440] Step 5: Synthesis of 1246-A1 Reaction scheme: [ka]

[0441] Testing Procedure: 5-Hydroxymethyl-2,2-dimethyl-1,3-dioxane (13.0 g, 88.9 mmol) and DCM (270 mL) were added to a 500 mL two-neck flask. The reaction mixture was cooled to -10 °C with stirring, and linoleic acid (25.0 g, 88.9 mmol), EDCI (25.6 g, 133.5 mmol), DMAP (2.18 g, 17.8 mmol), and pyridine (10.6 g, 134.0 mmol) were added. The mixture was warmed to room temperature for 8 h, quenched by adding 200 mL of water, and extracted twice with 200 mL of DCM. The combined organic phase was concentrated under reduced pressure to give crude 1246-A1. This was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 20:1 to give 23.6 g of 1246-A1 in 64.9% yield.

[0442] Step 6: Synthesis of 1246-A Reaction scheme: [ka]

[0443] Testing Procedure: 1246-A1 (23.6 g, 57.8 mmol) and ethanol (360 mL) were added to a 1 L round-bottom flask and stirred at room temperature. Hydrochloric acid (120 mL) was added dropwise and the mixture was allowed to react at room temperature for 1 hour. The reaction mixture was quenched by adding 600 mL of saturated sodium bicarbonate solution and extracted twice with 500 mL of DCM. The combined organic phase was concentrated under reduced pressure to give crude 1246-A. This was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 3:1 to give 17.5 g of 1246-A in 82.2% yield.

[0444] Step 7: Synthesis of 1246-A-TBS Reaction scheme: [ka]

[0445] Testing Procedure: 1246-A (21.3 g, 57.8 mmol) and DCM (600 mL) were added to a 1 L round-bottom flask. The reaction mixture was cooled to 0 °C with stirring, and imidazole (5.9 g, 86.7 mmol) and TBSCl (9.6 g, 63.7 mmol) were added. The mixture was allowed to react at 0 °C for 8 h. The reaction mixture was quenched by adding 500 mL of saturated sodium bicarbonate solution and extracted twice with DCM (500 mL). The combined organic phases were washed with 400 mL of saturated sodium chloride solution and then concentrated under reduced pressure to obtain the crude product. This product was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 10:1 to obtain 12.4 g of 1246-A-TBS in 44.4% yield.

[0446] Step 8: Synthesis of 1246-B Reaction scheme: [ka]

[0447] Testing Procedure: 1246-A-TBS (4.5 g, 9.32 mmol), DCM (45 mL), and DMAP (0.34 g, 2.79 mmol) were added to a 100 mL two-neck flask, and pyridine (1.62 g, 20.5 mmol) was added dropwise with stirring. p-Nitrophenyl chloroformate (3.75 g, 18.6 mmol) was slowly added in small portions and the mixture was allowed to react at room temperature for 1 hour. A mixed solution of 3-diethylamino-1-propanol (3.66 g, 27.9 mmol) and triethylamine (0.93 g, 9.32 mmol) was added and the mixture was allowed to react at room temperature for 16 hours. The solvent was evaporated under reduced pressure, and 200 mL of water was added. The mixture was extracted twice with 200 mL of n-hexane. The combined organic phase was washed with 200 mL of water and 150 mL of saturated sodium bicarbonate solution. It was then concentrated under reduced pressure to give 5.72 g of an oil.

[0448] The above oil (5.72 g) and tetrahydrofuran (57 mL) were added to a 250 mL round-bottom flask and stirred at room temperature. Triethylamine trihydrofluoride (14.35 g) was added dropwise and the mixture was allowed to react at room temperature for 16 hours. The reaction solution was concentrated, diluted with 100 mL of ethyl acetate, adjusted to pH 8 with saturated sodium bicarbonate solution, and washed with 200 mL of water. The aqueous phase was extracted twice with 200 mL of ethyl acetate. The combined organic phases were concentrated under reduced pressure to give crude 1246-B. This was purified by silica gel column chromatography eluting with DCM:methanol = 10:1 to give 960 mg of 1246-B in a 19.6% yield.

[0449] Step 9: Synthesis of 1246-C Reaction scheme: [ka]

[0450] Testing Procedure: 4,4-Dioctyloxy-1-butanol (1.0 g, 3.02 mmol), DCM (10 mL), DMAP (74 mg, 0.6 mmol), and pyridine (0.36 g, 4.5 mmol) were added to a 25 mL single-neck flask and stirred at room temperature. p-Nitrophenyl chloroformate (0.91 g, 4.5 mmol) was slowly added in small portions and allowed to react at room temperature for 1 hour. The reaction solution was concentrated, 100 mL of water was added, and the mixture was extracted twice with 100 mL of n-hexane. The combined organic phases were washed with 150 mL of water and 150 mL of saturated sodium bicarbonate solution, then concentrated under reduced pressure to give crude 1246-C. This was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 1:1 to give 905 mg of 1246-C in 60.3% yield.

[0451] Step 10: Synthesis of amino lipid compound 1246 Reaction scheme: [ka]

[0452] Testing Procedure: 1246-B (0.96 g, 1.82 mmol), DCM (10 mL), DMAP (67 mg, 0.55 mmol), and triethylamine (0.45 mL, 3.65 mmol) were added to a 25 mL two-neck flask and stirred at room temperature. 1246-C (0.91 g, 1.82 mmol) was added and the mixture was allowed to react at room temperature for 12 hours. 100 mL of water was added to the mixture, which was then extracted with 50 mL of DCM. The aqueous phase was extracted twice with 100 mL of DCM. The combined organic phases were washed with 150 mL of saturated sodium bicarbonate solution. The mixture was then concentrated under reduced pressure to give crude amino lipid compound 1246. This was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 1:1, yielding 1.25 g of amino lipid compound 1246 in 77.6% yield and 94.13% purity.

[0453] 1H NMR (600 MHz, CDCl3) δ 5.41-5.29 (m, 4H), 4.47 (t, J = 5.5 Hz, 1H), 4.22-4.12 (m, 10H), 3.55 (dt, J = 9.2, 6.7 Hz, 2H), 3.40 (dt, J = 9.2, 6.7 Hz, 2H), 2.76 (t, J = 6.9 Hz, 2H), 2.50 (q, J = 7.2 Hz, 6H), 2.45 (dt, J = 11.9, 5.9 Hz, 1H), 2.30 (t, J = 7.6 Hz, 2H), 2.04 (q, J = 7.0 Hz, 4H), 1.84-1.77 (m, 2H), 1.77-1.64 (m, 4H), 1.63-1.58 (m, 2H), 1.58-1.51 (m, 4H), 1.39-1.20 (m, 34H), 1.00 (t, J = 7.1 Hz, 6H), 0.88 (q, J = 6.9 Hz, 9H). 13 C NMR (151 MHz, CDCl3) δ 173.60, 155.13, 155.11, 130.36, 130.18, 128.18, 128.05, 102.70, 68.30, 67.12, 66.00, 65.03, 65.00, 61.39, 49.21, 47.01, 37.75, 34.23, 31.98, 31.66, 30.02, 29.93, 29.75, 29.58, 29.49, 29.41, 29.32, 29.26, 27.34, 26.60, 26.40, 25.77, 24.98, 24.20, 22.80, 22.71, 14.24, 14.22, 11.87. LC-MS (ESI): (M+H) calculated 882.7, found 883.1.

[0454] Example 5: Synthesis of amino lipid compound 1247 According to the general synthesis process and the method of Example 3, amino lipid compound 1247 was prepared according to the following reaction scheme to obtain 2.0 g of amino lipid compound 1247 with a yield of 54.9% and a purity of 95.75%.

change

[0455] 1 H NMR (600 MHz, CDCl3) δ 5.41-5.29 (m, 4H), 4.58 (t, J = 5.8 Hz, 1H), 4.22-4.14 (m, 5H), 4.11 (dd, J = 11.1, 6.4 Hz, 1H), 3.56 (dt, J = 9.2, 6.7 Hz, 2H), 3.46 (dd, J = 13.7, 6.1 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 2H), 2.77 (t, J = 6.9 Hz, 2H), 2.62-2.49 (m, 6H), 2.33-2.28 (m, 3H), 2.04 (q, J = 7.0 Hz, 4H), 1.85 (q, J = 6.2 Hz, 2H), 1.83-1.78 (m, 2H), 1.63-1.58 (m, 2H), 1.58-1.52 (m, 4H), 1.38-1.22 (m, 34H), 1.00 (t, J = 7.1 Hz, 6H), 0.88 (q, J = 7.0 Hz, 9H). 13 C NMR (151 MHz, CDCl3) δ 173.74, 155.31, 130.36, 130.18, 128.19, 128.05, 100.79, 68.34, 67.59, 66.95, 66.28, 66.27, 65.88, 62.18, 49.23, 47.01, 38.65, 34.33, 34.09, 31.99, 31.67, 30.07, 29.76, 29.60, 29.49, 29.44, 29.34, 29.29, 29.28, 27.34, 26.62, 26.42, 25.77, 25.05, 22.81, 22.72, 14.24, 14.22, 11.88. LC-MS(ESI): (M+H) calculated value 824.7, measured value 825.1.

[0456] Example 6: Synthesis of amino lipid compound 1248 According to the general synthesis process and the method of Example 3, amino lipid compound 1248 was prepared according to the following reaction scheme, and 5.47 g of amino lipid compound 1248 was obtained with a yield of 82.6% and a purity of 96.52%. [ka]

[0457] 1 H NMR (600 MHz, CDCl3) δ 5.41-5.19 (m, 4H), 4.44 (t, J = 5.7 Hz, 1H), 4.23-4.14 (m, 5H), 4.11 (dd, J = 11.2, 6.4 Hz, 1H), 3.55 (dt, J = 9.2, 6.7 Hz, 2H), 3.44 (d, J = 5.9 Hz, 2H), 3.42-3.36 (m, 4H), 2.77 (t, J = 6.8 Hz, 2H), 2.62-2.49 (m, 6H), 2.33-2.28 (m, 3H), 2.04 (q, J = 7.0 Hz, 4H), 1.83-1.77 (m, 2H), 1.63-1.58 (m, 4H), 1.58-1.52 (m, 6H), 1.41-1.21 (m, 36H), 1.00 (t, J = 7.1 Hz, 6H), 0.88 (q, J = 6.9 Hz, 9H). 13 C NMR (151 MHz, CDCl3) δ 173.75, 155.31, 130.36, 130.18, 128.18, 128.05, 103.14, 71.44, 68.26, 66.93, 65.93, 65.73, 62.23, 49.23, 47.02, 38.69, 34.34, 33.42, 31.99, 31.67, 30.06, 29.76, 29.59, 29.57, 29.49, 29.43, 29.34, 29.28, 27.34, 26.62, 26.42, 25.77, 25.05, 22.81, 22.72, 21.52, 14.25, 14.22, 11.89. LC-MS (ESI): (M+H) calculated 852.7, found 853.1.

[0458] Example 7: Synthesis of amino lipid compound 387 [ka]

[0459] According to the general synthesis process, amino lipid compound 387 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 387-A5, to obtain 0.37 g of amino lipid compound 387 from 387-A5 (1.7 g, 1.76 mmol) and 3-diethylamino-1-propanol (1.39 g, 10.56 mmol) in a yield of 21.93% and a purity of 95.40%. 1 H NMR (600 MHz, CDCl3) δ 4.67 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.55-2.47 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.85-1.76 (m, 2H), 1.74-1.63 (m, 8H), 1.63-1.48 (m, 16H), 1.38-1.20 (m, 36H), 1.00 (t, J = 7.1 Hz, 6H), 0.90 (m, 12H). LC-MS (ESI): (M+H) calculated 958.79, found 959.3.

[0460] Example 8: Synthesis of amino lipid compound 388 [ka]

[0461] Following the general synthesis process, amino lipid compound 388 was synthesized according to the procedure of Step 4 of Example 1, substituting 383-D compound 388-A5 to give 0.37 g of amino lipid compound 388 from 388-A5 (1.2 g, 1.17 mmol) and 3-dimethylamino-1-propanol (0.72 g, 7.02 mmol) in a yield of 31.95% and a purity of 94.45%. 1 H NMR (600 MHz, CDCl3) δ 4.71-4.63 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.08 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.3, 6.7 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.39-2.34 (m, 2H), 2.28 (t, J = 7.6 Hz, 4H), 2.22 (s, 6H), 1.88-1.80 (m, 2H), 1.74-1.63 (m, 10H), 1.63-1.47 (m, 16H), 1.39-1.22 (m, 42H), 0.95-0.81 (m, 12H). LC-MS (ESI): (M+H) calculated 986.82, found 987.4.

[0462] Example 9: Synthesis of amino lipid compound 389 [ka]

[0463] According to the general synthesis process, amino lipid compound 389 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 389-A5 to obtain 1.05 g of amino lipid compound 389 from 389-A5 (2.4 g, 2.23 mmol) and 3-diethylamino-1-propanol (1.75 g, 13.35 mmol) in a yield of 43.97% and a purity of 92.22%. 1H NMR (600 MHz, CDCl3) δ 4.72-4.62 (m, 1H), 4.45 (t, J = 5.7 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.05 (t, J = 6.7 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.61-2.43 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.87-1.76 (m, 2H), 1.57 (m, 26H), 1.43-1.16 (m, 50H), 1.01 (t, J = 7.1 Hz, 6H), 0.89 (t, J = 6.9 Hz, 12H). LC-MS (ESI): (M+H) calculated 1070.67, observed.

[0464] Example 10: Synthesis of amino lipid compound 390 [ka]

[0465] According to the general synthesis process, amino lipid compound 390 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 390-A5, to obtain 0.44 g of amino lipid compound 390 from 390-A5 (1.2 g, 1.17 mmol) and 3-diethylamino-1-propanol (0.92 g, 7.02 mmol) in a yield of 37.06% and a purity of 91.06%. 1H NMR (600 MHz, CDCl3) δ 4.71-4.61 (m, 1H), 4.45 (t, J = 5.7 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.05 (t, J = 6.7 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.51 (td, J = 7.1, 3.4 Hz, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.85-1.76 (m, 2H), 1.76-1.47 (m, 26H), 1.43-1.17 (m, 42H), 1.01 (t, J = 7.1 Hz, 6H), 0.90 (m, 12H). LC-MS (ESI): (M+H) calculated 1014.85, found 1015.3.

[0466] Example 11: Synthesis of amino lipid compound 391 [ka]

[0467] According to the general synthesis process, amino lipid compound 391 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 391-A5, to obtain 0.847 g of amino lipid compound 391 from 391-A5 (2 g, 2.03 mmol) and 3-diethylamino-1-propanol (1.6 g, 12.18 mmol) in a yield of 43.53% and a purity of 92.68%. 1H NMR (600 MHz, CDCl3) δ 4.71-4.61 (m, 1H), 4.45 (t, J = 5.7 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.05 (t, J = 6.7 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.51 (td, J = 7.1, 3.4 Hz, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.85-1.76 (m, 2H), 1.76-1.47 (m, 26H), 1.43-1.17 (m, 34H), 1.01 (t, J = 7.1 Hz, 6H), 0.90 (m, 12H). LC-MS (ESI): (M+H) calculated 958.46, found 959.1.

[0468] Example 12: Synthesis of amino lipid compound 392 [ka]

[0469] According to the general synthesis process, amino lipid compound 392 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 392-A5, to obtain 0.29 g of amino lipid compound 392 from 392-A5 (0.86 g, 0.85 mmol) and 3-diethylamino-1-propanol (0.67 g, 5.1 mmol) in a yield of 33.9% and a purity of 97.93%. 1H NMR (600 MHz, CDCl3) δ 5.62-5.48 (m, 8H), 4.69-4.65 (m, 1H), 4.62-4.53 (m, 2H), 4.20-4.11 (m, 6H), 4.09-4.06 (m, 8H), 2.54-2.45 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 2.06-2.03 (m, 8H), 1.84-1.76 (m, 2H), 1.75-1.66 (m, 8H), 1.64-1.46 (m, 8H), 1.43-1.35 (m, 8H), 1.35-1.22 (m, 20H), 1.00 (t, J = 7.1 Hz, 6H), 0.90 (t, J = 7.4 Hz, 12H). LC-MS (ESI): (M+H) calculated 1006.50, found 1007.1. Example 13: Synthesis of amino lipid compound 396 [ka]

[0470] According to the general synthesis process, amino lipid compound 396 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 396-A5, to obtain 0.29 g of amino lipid compound 396 from 396-A5 (1.3 g, 1.27 mmol) and 1-(3-hydroxypropyl)pyrrolidine (0.67 g, 5.18 mmol) in a yield of 22.55% and a purity of 95.18%. 1H NMR (600 MHz, CDCl3) δ 4.71-4.62 (m, 1H), 4.48 (t, J = 5.2 Hz, 2H), 4.18 (t, J = 6.6 Hz, 2H), 4.07 (t, J = 6.1 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.55-2.49 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.92-1.97 (m, 2H), 1.80-1.63 (m, 14H), 1.63-1.45 (m, 16H), 1.43-1.16 (m, 42H), 0.89 (t, J = 6.9 Hz, 12H). LC-MS (ESI): (M+H) calculated 1012.55, found 1013.2.

[0471] Example 14: Synthesis of amino lipid compound 398 [ka]

[0472] According to the general synthesis process, amino lipid compound 398 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 398-A5, to obtain 0.29 g of amino lipid compound 398 from 398-A5 (1 g, 0.98 mmol) and N-methyl-2-(2-hydroxyethyl)pyrrolidine (0.76 g, 5.88 mmol) in a yield of 29.23% and a purity of 96.77%. 1H NMR (600 MHz, CDCl3) δ 4.72-4.62 (m, 1H), 4.48 (d, J = 5.3 Hz, 2H), 4.25-4.18 (m, 1H), 4.18-4.12 (m, 1H), 4.07 (t, J = 6.0 Hz, 4H), 3.56 (dt, J = 8.5, 6.7 Hz, 4H), 3.40 (dt, J = 8.9, 6.8 Hz, 4H), 3.05 (t, J = 8.6 Hz, 1H), 2.28 (dd, J = 16.8, 9.3 Hz, 7H), 2.20-2.02 (m, 3H), 2.00-1.94 (m, 1H), 1.83-1.63 (m, 12H), 1.63-1.43 (m, 18H), 1.40-1.19 (m, 42H), 0.88 (t, J = 6.9 Hz, 12H). LC-MS (ESI): (M+H) calculated 1012.55, found 1013.2.

[0473] Example 15: Synthesis of amino lipid compound 399 [ka]

[0474] According to the general synthesis process, amino lipid compound 399 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 399-A5, to obtain 0.7 g of amino lipid compound 399 from 399-A5 (1 g, 0.98 mmol) and 3-(2-methylpiperidin-1-yl)propan-1-amine (0.92 g, 5.88 mmol) in a yield of 68.71% and a purity of 96.77%. 1H NMR (600 MHz, CDCl3) δ 4.69 (s, 1H), 4.48-4.47 (m, 2H), 4.08-4.06 (t, J = 5.9 Hz, 4H), 3.56 (dt, J = 13.6, 6.7 Hz, 4H), 3.40 (dt, J = 13.8, 6.8 Hz, 4H), 3.32-3.21 (m, 1H), 3.17-3.16 (m, 1H), 2.85-2.83 (m, 1H), 2.79-2.74 (m, 1H), 2.28 (t, J = 7.5 Hz, 6H), 2.06 (t, J = 10.7 Hz, 1H), 1.81-1.41 (m, 30H), 1.37-1.27 (m, 46H), 1.04 (d, J = 6.2 Hz, 3H), 0.89 (t, J = 6.8 Hz, 12H). LC-MS (ESI): (M+H) calculated 1039.62, found 1040.3.

[0475] Example 16: Synthesis of amino lipid compound 416 [ka]

[0476] According to the general synthesis process, amino lipid compound 416 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 416-A5, to obtain 0.6 g of amino lipid compound 416 from 416-A5 (1 g, 0.98 mmol) and 1-methylpiperidine-3-methanol (0.76 g, 5.88 mmol) in a yield of 60.47% and a purity of 96.77%. 1H NMR (600 MHz, CDCl3) δ 4.70-4.62 (m, 1H), 4.48 (t, J = 5.2 Hz, 2H), 4.08-4.03 (m, 5H), 3.94 (dd, J = 10.6, 7.4 Hz, 1H), 3.56 (dt, J = 9.2, 6.7 Hz, 4H), 3.40 (dt, J = 9.2, 6.7 Hz, 4H), 2.85 (d, J = 10.2 Hz, 1H), 2.74 (d, J = 10.5 Hz, 1H), 2.29-2.25 (m, 7H), 2.06-1.94 (m, 1H), 1.90 (t, J = 10.8 Hz, 1H), 1.80-1.44 (m, 29H), 1.42-1.08 (m, 44H), 0.89 (t, J = 6.9 Hz, 12H). LC-MS (ESI): (M+H) calculated 1012.55, found 1013.2.

[0477] Example 17: Synthesis of amino lipid compound 423 [ka]

[0478] According to the general synthesis process, amino lipid compound 423 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 423-A5, to obtain 0.7 g of amino lipid compound 423 from 423-A5 (1 g, 0.98 mmol) and 3-dimethylamino-2,2-dimethyl-1-propanol (0.77 g, 5.88 mmol) in a yield of 70.4% and a purity of 91.78%. 1H NMR (600 MHz, CDCl3) δ 4.72-4.63 (m, 1H), 4.48 (t, J = 5.2 Hz, 2H), 4.08 (t, J = 6.1 Hz, 4H), 3.94 (s, 2H), 3.57 (dt, J = 9.1, 6.7 Hz, 4H), 3.41 (dt, J = 9.2, 6.7 Hz, 4H), 2.30-2.23 (m, 10H), 2.17 (s, 2H), 1.75-1.47 (m, 26H), 1.42-1.17 (m, 42H), 0.92 (s, 6H), 0.89 (t, J = 6.9 Hz, 12H) LC-MS (ESI): (M+H) calculated 1014.57, found 1015.2.

[0479] Example 18: Synthesis of amino lipid compound 429 [ka]

[0480] According to the general synthesis process, amino lipid compound 429 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 429-A5, to obtain 0.84 g of amino lipid compound 429 from 429-A5 (2 g, 1.94 mmol) and 3-diethylamino-1-propanol (1.53 g, 11.64 mmol) in a yield of 42.35% and a purity of 97.22%. 1H NMR (600 MHz, CDCl3) δ 4.71-4.62 (m, 1H), 4.48 (t, J = 5.1 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.07 (t, J = 6.0 Hz, 4H), 3.67 (dt, J = 9.3, 6.3 Hz, 4H), 3.55-3.36 (m, 20H), 2.53 (td, J = 7.1, 3.4 Hz, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.86-1.81 (m, 10H), 1.73-1.63 (m, 8H), 1.63-1.45 (m, 8H), 1.27 (m, 20H), 1.19 (t, J = 7.0 Hz, 12H), 1.03-1.00 (m, 6H). LC-MS (ESI): (M+H) calculated 1022.45, found 1023.1.

[0481] Example 19: Synthesis of amino lipid compound 430 [ka]

[0482] According to the general synthesis process, amino lipid compound 430 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 430-A5, to obtain 0.84 g of amino lipid compound 430 from 430-A5 (2.3 g, 1.7 mmol) and 3-diethylamino-1-propanol (1.34 g, 10.2 mmol) in a yield of 36.7% and a purity of 98.29%. 1H NMR (600 MHz, CDCl3) δ 4.70-4.63 (m, 1H), 4.43 (t, J = 5.2 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.46 (dd, J = 9.2, 5.8 Hz, 4H), 3.27 (dd, J = 9.2, 5.8 Hz, 4H), 2.57-2.45 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.86-1.76 (m, 2H), 1.74-1.45 (m, 24H), 1.42-1.18 (m, 80H), 1.01 (t, J = 7.1 Hz, 6H), 0.89 (q, J = 6.9 Hz, 24H). LC-MS (ESI): (M+H) calculated 1351.21, found 1351.8.

[0483] Example 20: Synthesis of amino lipid compound 490 [ka]

[0484] According to the general synthesis process, amino lipid compound 490 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 490-A5, to obtain 1.3 g of amino lipid compound 490 from 490-A5 (2.9 g, 2.69 mmol) and 3-dimethylamino-1-propanol (1.67 g, 16.14 mmol) in a yield of 46.35% and a purity of 93.50%. 1H NMR (600 MHz, CDCl3) δ 4.67 (s, 1H), 4.47 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.37-2.34 (m, 2H), 2.28 (t, J = 7.6 Hz, 4H), 2.22 (s, 6H), 1.87-1.81 (m, 2H), 1.68 (t, J = 6.6 Hz, 12H), 1.56 (dt, J = 14.5, 4.6 Hz, 12H), 1.34-1.24 (m, 52H), 0.88 (t, J = 7.0 Hz, 12H). LC-MS (ESI): calculated 1042.62, found (M+H): 1043.4.

[0485] Example 21: Synthesis of Aminolipid Compound 849 [ka]

[0486] According to the general synthesis process, amino lipid compound 849 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 849-A5, to obtain 0.8 g of amino lipid compound 849 from 849-A5 (2.0 g, 1.68 mmol) and 3-dimethylamino-1-propanol (1.04 g, 10.08 mmol) in a yield of 41.2% and a purity of 93.97%. 1H NMR (600 MHz, CDCl3) δ 4.66 (m, 1H), 4.47 (t, J = 5.2 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.07 (t, J = 6.1 Hz, 4H), 3.55 (dt, J = 9.2, 6.7 Hz, 4H), 3.40 (dt, J = 9.2, 6.7 Hz, 4H), 2.38-2.33 (m, 2H), 2.27 (t, J = 7.6 Hz, 4H), 2.22 (s, 6H), 1.87-1.80 (m, 2H), 1.71-1.63 (m, 8H), 1.63-1.49 (m, 16H), 1.37-1.20 (m, 66H), 0.87 (t, J = 7.0 Hz, 12H). LC-MS (ESI): (M+H) calculated 1154.84, found 1155.5.

[0487] Example 22: Synthesis of Aminolipid Compound 859 [ka]

[0488] According to the general synthesis process, amino lipid compound 859 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 859-A5 to obtain 270 mg of amino lipid compound 859 from 859-A5 (1.1 g, 0.97 mmol) and 3-diethylamino-1-propanol (0.76 g, 5.82 mmol) in a yield of 24.72% and a purity of 95.67%. 1H NMR (600 MHz, CDCl3) δ 4.72-4.59 (m, 1H), 4.48 (t, J = 5.1 Hz, 2H), 4.17 (t, J = 6.5 Hz, 2H), 4.08 (t, J = 6.1 Hz, 4H), 3.56 (dt, J = 9.1, 6.7 Hz, 4H), 3.40 (dt, J = 9.1, 6.7 Hz, 4H), 2.51 (td, J = 7.1, 3.4 Hz, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.84-1.77 (m, 2H), 1.73-1.50 (m, 28H), 1.31 (dd, J = 30.6, 6.5 Hz, 56H), 1.01 (t, J = 7.1 Hz, 6H), 0.88 (t, J = 7.0 Hz, 12H). LC-MS (ESI): Calculated value 1126.78, found value (M+H): 1127.4.

[0489] Example 23: Synthesis of amino lipid compound 2021

change

[0490] Step 1: Synthesis of 2021-A2

change

[0491] DCM (120 ml) and TEA (4.18 g, 41.75 mmol) were added to EDCI (8.0 g, 41.75 mmol), followed by 2021-A1 (9.6 g, 33.4 mmol) with stirring at room temperature. After the reaction solution became clear, 2-hydroxymethyl-1,3-propanediol (1.8 g, 16.7 mmol) and DMAP (377 mg, 3.09 mmol) were added and the mixture was allowed to react at room temperature for 16 hours. The reaction solution was washed with saturated potassium bicarbonate solution (150 ml) and separated. The organic phase was collected, and the aqueous phase was extracted once with DCM (80 ml). The organic phases were combined, and the solvent was evaporated under reduced pressure to obtain crude 2021-A2. This was purified by silica gel column chromatography eluting with n-hexane:ethyl acetate = 20:1 to obtain 4.5 g of 2021-A2 in a 41.65% yield.

[0492] Step 2: Synthesis of 2021-A3 [ka]

[0493] 2012-A2 (2.0 g, 3.09 mmol) was placed in a 50 mL single-neck round-bottom flask and dissolved in DCM (20 mL). DMAP (113 mg, 0.93 mmol) and pyridine (0.61 g, 7.73 mmol) were added and stirred at room temperature. p-Nitrophenyl chloroformate (1.25 g, 6.18 mmol) was added portionwise and stirred for an additional 1 h. The mixture was diluted with water (150 mL) and extracted with DCM (100 mL). The organic phase was collected, washed with water (80 mL), and concentrated to give 3.5 g of crude 2021-A3. This was purified by silica gel column chromatography eluting with ethyl acetate:n-heptane = 1.5:1 to give 2.13 g of 2021-A3 in 85% yield.

[0494] Step 3: Synthesis of 2021 [ka]

[0495] 2021-A3 (2.0 g, 2.46 mmol) was added to a 50 mL single-neck round-bottom flask and dissolved in DCM (20 mL). DMAP (92 mg, 0.75 mmol), triethylamine (0.75 mg, 7.38 mmol), and dimethylaminopropanol (1.52 g, 14.76 mmol) were added and stirred at room temperature for 2 days. The mixture was diluted with water (100 mL) and extracted with dichloromethane (100 mL). The organic phase was collected, washed with water (80 mL), and concentrated under reduced pressure to give 2.6 g of crude 2021. This was purified by silica gel column chromatography eluting with ethyl acetate:n-heptane = 1.5:1 to give 1.16 g of amino lipid compound 2021 in 61% yield and 95.32% purity. 1 H NMR (600 MHz, CDCl3) δ 4.47 (t, J = 5.6 Hz, 2H), 4.18 (t, J = 6.1 Hz, 4H), 4.13 (dd, J = 6.0, 1.8 Hz, 4H), 3.55 (dt, J = 9.3, 6.7 Hz, 4H), 3.39 (dt, J = 9.3, 6.7 Hz, 4H), 2.43-2.37 (m, 5H), 2.36-2.32 (m, 2H), 2.21 (s, 6H), 1.91 (td, J = 7.6, 5.7 Hz, 4H), 1.85-1.80 (m, 2H), 1.57-1.51 (m, 8H), 1.35-1.24 (m, 24H), 0.88 (t, J = 7.0 Hz, 12H). LC-MS (ESI): calculated 776.11, found (M+H): 776.7.

[0496] Example 24: Synthesis of amino lipid compound 2035 [ka]

[0497] According to the general synthesis process, amino lipid compound 2035 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2035-A5 to give 3.0 g of amino lipid compound 2035 from 2035-A5 (4.1 g, 4.12 mmol) and 3-dimethylamino-1-propanol (2.55 g, 24.6 mmol) in a yield of 75.97% and a purity of 92.02%. 1 H NMR (600 MHz, CDCl3) δ 4.71-4.63 (m, 1H), 4.60 (t, J = 5.8 Hz, 2H), 4.23-4.10 (m, 6H), 3.58 (dt, J = 9.2, 6.7 Hz, 4H), 3.42 (dt, J = 9.2, 6.7 Hz, 4H), 2.47-2.38 (m, 2H), 2.32-2.24 (m, 10H), 1.94 (q, J = 6.4 Hz, 4H), 1.90-1.81 (m, 2H), 1.63-1.49 (m, 16H), 1.38-1.22 (m, 44H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): (M+H) calculated 958.46, found 959.2.

[0498] Example 25: Synthesis of amino lipid compound 2036 [ka]

[0499] According to the general synthesis process, amino lipid compound 2036 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2036-A5, to obtain 0.9 g of amino lipid compound 2036 from 2036-A5 (4.85 g, 4.62 mmol) and 3-dimethylamino-1-propanol (2.86 g, 27.7 mmol) in a yield of 19.2% and a purity of 92.23%. 1H NMR (600 MHz, CDCl3) δ 4.67 (m, 1H), 4.46 (t, J = 5.7 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.06 (t, J = 6.7 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.40 (dt, J = 9.3, 6.7 Hz, 4H), 2.39-2.34 (m, 2H), 2.28 (t, J = 7.6 Hz, 4H), 2.22 (s, 6H), 1.84 (dd, J = 14.2, 7.1 Hz, 2H), 1.66-1.54 (m, 30H), 1.45-1.27 (m, 42H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): (M+H) calculated 1014.57, found 1015.3.

[0500] Example 26: Synthesis of amino lipid compound 2038 [ka]

[0501] According to the general synthesis process, amino lipid compound 2038 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2038-A5, to obtain 425 mg of amino lipid compound 2038 from 2038-A5 (0.91 g, 1.02 mmol) and 3-dimethylamino-1-propanol (0.63 g, 6.12 mmol) in a yield of 47.77% and a purity of 94.67%. 1H-NMR (600 MHz, CDCl3) δ 4.70-4.63 (m, 1H), 4.48 (t, J = 5.2 Hz, 2H), 4.22 (t, J = 5.8 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.2, 6.7 Hz, 4H), 3.41 (dt, J = 9.2, 6.7 Hz, 4H), 2.65-2.57 (m, 4H), 2.30 (ddd, J = 15.3, 11.8, 6.9 Hz, 14H), 1.70-1.54 (m, 20H), 1.38-1.27 (m, 28H), 0.89 (t, J = 6.9 Hz, 12H). LC-MS (ESI): calculated 874.29, found (M+H): 875.1.

[0502] Example 27: Synthesis of amino lipid compound 2039 [ka]

[0503] According to the general synthesis process, amino lipid compound 2039 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2039-A5 to give 1.05 g of amino lipid compound 2039 from 2039-A5 (5.0 g, 5.33 mmol) and 3-dimethylamino-1-propanol (3.3 g, 31.97 mmol) in a yield of 21.83% and a purity of 94.51%. 1H NMR (600 MHz, CDCl3) δ 4.67 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.08 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.3, 6.7 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.38-2.35 (m, 2H), 2.31-2.26 (m, 4H), 2.23 (s, 6H), 1.85 (dt, J = 13.8, 6.7 Hz, 4H), 1.73-1.65 (m, 8H), 1.58 (m, 16H), 1.57 -1.39-1.25 (m, 30H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): calculated 902.35, found (M+H): 903.30.

[0504] Example 28: Synthesis of amino lipid compound 2040 [ka]

[0505] According to the general synthesis process, amino lipid compound 2040 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2040-A5, to give 0.77 g of amino lipid compound 2040 from 2040-A5 (2.0 g, 2.07 mmol) and 3-dimethylamino-1-propanol (1.28 g, 12.42 mmol) in a yield of 40.0% and a purity of 92.49%. 1H NMR (600 MHz, CDCl3) δ 4.68 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.08 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.3, 6.7 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.38-2.35 (m, 2H), 2.31-2.26 (m, 4H), 2.23 (s, 6H), 1.85 (dt, J = 13.8, 6.7 Hz, 4H), 1.73-1.65 (m, 8H), 1.58 (m, 16H), 1.39-1.25 (m, 34H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): calculated 930.40, found (M+H): 931.2.

[0506] Example 29: Synthesis of amino lipid compound 2041 [ka]

[0507] According to the general synthesis process, amino lipid compound 2041 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2041-A5, to obtain 0.66 g of amino lipid compound 2041 from 2041-A5 (2.5 g, 2.51 mmol) and 3-dimethylamino-1-propanol (1.56 g, 15.08 mmol) in a yield of 27.43% and a purity of 91.97%. 1H NMR (600 MHz, CDCl3) δ 4.68 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.56-2.46 (m, 6H), 2.32-2.24 (m, 4H), 1.71-1.66 (m, 12H), 1.62 (m, 4H), 1.59-1.54 (m, 10H), 1.40-1.25 (m, 40H), 1.01 (t, J = 7.1 Hz, 6H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): (M+H) calculated 958.46, found 959.0.

[0508] Example 30: Synthesis of amino lipid compound 2042 [ka]

[0509] According to the general synthesis process, amino lipid compound 2042 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2038-A5 to give 0.35 g of amino lipid compound 2042 from 2038-A5 (1.0 g, 1.10 mmol) and 3-diethylamino-1-propanol (0.86 g, 6.60 mmol) in a yield of 35.26% and a purity of 96.36%. 1H NMR (600 MHz, CDCl3) δ 4.68 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.6 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.3, 6.7 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.56-2.46 (m, 6H), 2.32-2.24 (m, 4H), 1.71-1.66 (m, 12H), 1.62 (m, 4H), 1.59-1.54 (m, 10H), 1.40-1.25 (m, 28H), 1.01 (t, J = 7.1 Hz, 6H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): calculated 902.35, found (M+H): 903.2.

[0510] Example 31: Synthesis of amino lipid compound 2043 [ka]

[0511] According to the general synthesis process, amino lipid compound 2043 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2039-A5, to give 0.56 g of amino lipid compound 2043 from 2039-A5 (1.2 g, 1.28 mmol) and 3-diethylamino-1-propanol (1.01 g, 7.67 mmol) in a yield of 47.02% and a purity of 90.21%. 1H NMR (600 MHz, CDCl3) δ 4.67 (m, 1H), 4.48 (t, J = 5.3 Hz, 2H), 4.17 (t, J = 6.4 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.3, 6.7 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.56-2.47 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.86-1.78 (m, 4H), 1.72-1.65 (m, 8H), 1.62-1.52 (m, 16H), 1.37-1.24 (m, 30H), 1.01 (t, J = 7.1 Hz, 6H), 0.89 (t, J = 7.0 Hz, 12H). LC-MS (ESI): calculated 930.40, found (M+H): 931.3.

[0512] Example 32: Synthesis of amino lipid compound 2044 [ka]

[0513] According to the general synthesis process, amino lipid compound 2044 was synthesized according to the procedure of Step 3 of Example 1, replacing 383-D with compound 2040-A5, to obtain 0.4 g of amino lipid compound 2044 from 2044-A5 (0.93 g, 0.96 mmol) and 3-diethylamino-1-propanol (0.76 g, 5.76 mmol) in a yield of 43.50% and a purity of 90.45%. 1H NMR (600 MHz, CDCl3) δ 4.71-4.60 (m, 1H), 4.48 (t, J = 5.1 Hz, 2H), 4.20-4.12 (m, 2H), 4.08 (t, J = 6.0 Hz, 4H), 3.57 (dt, J = 9.2, 6.7 Hz, 4H), 3.41 (dt, J = 9.3, 6.7 Hz, 4H), 2.57-2.45 (m, 6H), 2.28 (t, J = 7.6 Hz, 4H), 1.93-1.84 (m, 4H), 1.73-1.65 (m, 8H), 1.65-1.51 (m, 16H), 1.35-1.25 (m, 34H), 1.02 (t, J = 7.1 Hz, 6H), 0.89 (t, J = 6.8 Hz, 12H). LC-MS (ESI): calculated 958.46, found (M+H): 959.3.

[0514] Example 33: Synthesis of amino lipid compound 2045 [ka]

[0515] According to the general synthesis process, amino lipid compound 2045 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2041-A5, to give 1.2 g of amino lipid compound 2045 from 2045-A5 (2.5 g, 2.51 mmol) and 3-diethylamino-1-propanol (1.98 g, 15.08 mmol) in a yield of 48.46% and a purity of 90.78%. 1H NMR (600 MHz, CDCl3) δ 4.71-4.61 (m, 1H), 4.47 (t, J = 5.1 Hz, 2H), 4.16 (t, J = 6.5 Hz, 2H), 4.06 (t, J = 6.1 Hz, 4H), 3.56 (dt, J = 9.3, 6.7 Hz, 4H), 3.39 (dt, J = 9.3, 6.7 Hz, 4H), 2.58-2.43 (m, 6H), 2.27 (t, J = 7.6 Hz, 4H), 1.90-1.74 (m, 6H), 1.74-1.45 (m, 20H), 1.42-1.16 (m, 40H), 1.00 (t, J = 7.1 Hz, 6H), 0.88 (t, J = 6.8 Hz, 12H). LC-MS (ESI): (M+H) calculated 986.51, found 987.1.

[0516] Example 34: Synthesis of amino lipid compound 2061 [ka]

[0517] According to the general synthesis process, amino lipid compound 2061 was synthesized according to the procedure of Step 4 of Example 1, replacing 383-D with compound 2061-A5, to give 0.942 g of amino lipid compound 2061 from 2061-A5 (1.87 g, 1.99 mmol) and 3-diethylamino-1-propanol (1.23 g, 11.94 mmol) in a yield of 53.29% and a purity of 94.25%. 1H-NMR (600 MHz, CDCl3) δ 4.70-4.63 (m, 1H), 4.48 (t, J = 5.2 Hz, 2H), 4.22 (t, J = 5.8 Hz, 2H), 4.07 (t, J = 6.2 Hz, 4H), 3.57 (dt, J = 9.2, 6.7 Hz, 4H), 3.41 (dt, J = 9.2, 6.7 Hz, 4H), 2.65-2.57 (m, 4H), 2.30 (ddd, J = 15.3, 11.8, 6.9 Hz, 14H), 1.70-1.54 (m, 22H), 1.38-1.27 (m, 28H), 0.89 (t, J = 6.9 Hz, 12H). LC-MS (ESI): Calculated value 888.32, found value (M+H): 888.7.

[0518] Example 35: Synthesis of amino lipid compound 851

change

[0519] Step 1: Synthesis of 851-A1 Reaction scheme:

change

[0520] Testing Procedure: EDCI (2.8 g, 14.6 mmol), DCM (50 mL), and TEA (1.47 g, 14.6 mmol) were sequentially added to a 100 mL round-bottom flask and vigorously stirred for 5 minutes. Next, DMAP (0.89 g, 7.3 mmol), BHB (4,4-bis(heptyloxy)butanol) (3.09 g, 10.22 mmol), and DTN (10-oxononadecanedioic acid) (5.00 g, 14.6 mmol) were added and stirred at room temperature overnight. DCM (100 mL) and water (150 mL) were added and stirred, followed by extraction and separation. The organic phase was collected, washed with 50 mL of saturated sodium chloride solution, and then concentrated under reduced pressure to give 8.2 g of crude 851-A1. This was purified by silica gel column chromatography and eluted with ethyl acetate:n-heptane=2:1 to obtain 3.36 g of 851-A1 in a yield of 52.3%.

[0521] Step 2: Synthesis of 851-A2 Reaction scheme: [ka]

[0522] Testing Procedure: EDCI (1.1 g, 5.74 mmol), DCM (30 mL), and TEA (0.58 g, 5.74 mmol) were added sequentially to a 100 mL round-bottom flask and stirred vigorously for 5 min. Next, DMAP (0.29 g, 2.39 mmol), BPB (4,4-bis(pentyloxy)butanol) (1.41 g, 5.74 mmol), and 851-A1 (3.00 g, 4.78 mmol) were added and stirred at room temperature overnight. DCM (100 mL) and water (150 mL) were added and stirred, followed by extraction and separation. The organic phase was collected, washed with 50 mL of saturated sodium chloride solution, and concentrated under reduced pressure to give 4.8 g of crude 851-A2. This was purified by silica gel column chromatography and eluted with ethyl acetate:n-heptane=1.5:1 to obtain 3.42 g of 851-A2 in a yield of 83.6%.

[0523] Step 3: Synthesis of 851-A3 Reaction scheme: [ka]

[0524] Testing Procedure: 851-A2 (3.00 g, 3.51 mmol) was placed in a 250 mL single-neck flask, dissolved in methanol (30 mL), and cooled to 0 °C. Sodium borohydride (0.135 g, 3.51 mmol) was added portionwise with stirring, and the reaction was maintained for 1 h after the addition was complete. The solvent was removed under reduced pressure, and water (100 mL) and DCM (100 mL) were added and stirred for extraction. The organic phase was collected, washed with water (50 mL), and then concentrated under reduced pressure to give 3.1 g of crude 851-A3. This was purified by silica gel column chromatography eluting with ethyl acetate:n-heptane = 1.5:1 to give 2.86 g of 851-A3 in 95.1% yield.

[0525] Step 4: Synthesis of 851-A4 Reaction sche...

Claims

1. An amino lipid compound having the structure of formula (II-I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemical 1】 During the ceremony: A １ , A ２ , and A ３ is one of: (1) A １ and A ２ The dashed line connecting A and １ and A ３ If there is no dashed line connecting A and １ is H, C １ -C ５ Hydrocarbyl, or C １ -C ５ Heterohydrocarbyl, A ２ is H, C １ -C ５ Hydrocarbyl, or C １ -C ５ Heterohydrocarbyl, A ３ is C １ -C ５ is a hydrocarbylene or bond; (2) A １ and A ２ The dashed line connecting A and B is a bond. １ and A ３ If there is no dashed line connecting A and １ is C １ -C ５ Hydrocarbylene or C １ -C ５ Heterohydrocarbylene, A ２ is C １ -C ５ Hydrocarbylene or C １ -C ５ heterohydrocarbylene, and A ３ is C １ -C ５ A is a hydrocarbylene or bond; １ and A ２ together with the nitrogen atom to which they are both attached form a nitrogen-containing heterocycle; (3) A １ and A ３ The dashed line connecting A and B is a bond. １ and A ２ If there is no dashed line connecting A and １ is C １ -C ５ Hydrocarbylene or C １ -C ５ Heterohydrocarbylene, A ２ is H, C １ -C ５ Hydrocarbyl, or C １ -C ５ Heterohydrocarbyl, A ３ is C １ -C ５ A is hydrocarbylene; １ and A ３ together with the nitrogen atom to which they are both attached form a nitrogen-containing heterocycle; (4) A １ and A ２ The dashed line connecting A and １ and A ３ When the dashed line connecting A and B is a bond, １ is C １ -C ５ Hydrocarbylene or C １ -C ５ Heterohydrocarbylene, A ２ is C １ -C ５ Hydrocarbylene or C １ -C ５ Heterohydrocarbylene, A ３ is C １ -C ５ A is hydrocarbylene; １ , A ２ , and A ３ together with the nitrogen atom to which they are all attached, form a nitrogen-containing spiro heterocycle, a nitrogen-containing fused heterocycle, or a nitrogen-containing bridged heterocycle; A ４ is C １ -C ５ is a hydrocarbylene or bond; A ５ , A ６ , A ７ , A ８ , and A １２ are each independently １ -C １８ Hydrocarbylene, C １ -C １８ heterohydrocarbylene, or a bond; Z １ and Z ２ are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R ６ ) -, -N(R ６ )C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R ６ )C(=O)O-, -OC(=O)N(R ６ ) -, -N(R ６ )C(=O)N(R ６ )-, -SC(=O)N(R ６ ) -, -N(R ６ )C(=O)S-, -N(C(=O)A ９ Office Automation １０ )-,-N(C(=O)A ９ SA １０ )-,-N(C(=O)A １１ ), -N(A ９ Office Automation １０ ) -, -N(A ９ SA １０ ) -, -N(A １１ )-, -OS(=O)O-, -OS(=O) ２ O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O) ２ NH- or -NHS(=O) ２ is O-; Y １ は-Z ３ C(=O)Z ４ -、-N(R ５ )-、-Z ３ C(=S)Z ４ -、-OS(=O) ２ O-、-OS(=O)O-、-OS(=O) ２ NH-、-NHS(=O) ２ NH-、-NHS(=O) ２ -、-S(=O) ２ NH-、-S(=O) ２ O-、-OS(=O) ２ -、-OP(=O)O-、-OP(=O)(OH)O-、-OP(=O)(H)O-、-O-、-S-、-NHS(=O) ２ O-、-NKP(=O)O-、-OP(=O)N-、-NKP(=O)(OX)--、-OP(=O)(OX)N-、--C(=O)S-、-----OOOO----- X is C or N; R １ is H, C １ -C ２４ Hydrocarbyl, C １ -C ２４ Heterohydrocarbyl, Z ６ R ８ , -C(R ６ ) (OA １３ Z ８ R ９ ) ２ , -C(R ６ ) (SA １３ Z ８ R ９ ) ２ , or -C(R ６ ) (SA １３ Z ８ R ９ ) (OA １３ Z ８ R ９ ) and R ２ is H, C １ -C ２４ Hydrocarbyl, C １ -C ２４ Heterohydrocarbyl, Z ７ R １０ , -C(R ６ ) (OA １４ Z ９ R １１ ) ２ , -C(R ６ ) (SA １４ Z ９ R １１ ) ２ , or -C(R ６ ) (SA １４ Z ９ R １１ ) (OA １４ Z ９ R １１ ) and Z ３ and Z ４ are each independently —O—, —N(R ６ )-, -S-, or a bond; Z ６ and Z ７ are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R ６ ) -, -N(R ６ )C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R ６ )C(=O)O-, -OC(=O)N(R ６ ) -, -N(R ６ )C(=O)N(R ６ )-, -SC(=O)N(R ６ ) -, -N(R ６ )C(=O)S-, -N(C(=O)A ９ Office Automation １０ )-,-N(C(=O)A ９ SA １０ )-,-N(C(=O)A １１ ), -N(A ９ Office Automation １０ ) -, -N(A ９ SA １０ ) -, -N(A １１ )-, -OS(=O)O-, -OS(=O) ２ O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O) ２ NH- or -NHS(=O) ２ is O-; R ５ is -C(=O)A ９ Z ５ A １０ , -C(=O)A １１ , H, or C １ -C ８ is a hydrocarbyl; Z ５ is —O— or —S—; Z ８ and Z ９ are each independently -C(=O)O-, -OC(=O)-, -O-, -C(=O)-, -S-, -C(=O)S-, -SC(=O)-, -C(=O)N(R ６ ) -, -N(R ６ )C(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -N(R ６ )C(=O)O-, -OC(=O)N(R ６ ) -, -N(R ６ )C(=O)N(R ６ )-, -SC(=O)N(R ６ ) -, -N(R ６ )C(=O)S-, -N(C(=O)A ９ Office Automation １０ )-,-N(C(=O)A ９ SA １０ )-,-N(C(=O)A １１ ), -N(A ９ Office Automation １０ ) -, -N(A ９ SA １０ ) -, -N(A １１ )-, -OS(=O)O-, -OS(=O) ２ O-, -OP(=O)O-, -OP(=O)(OH)O-, -OP(=O)(H)O-, -OS(=O) ２ NH-, -NHS (=O) ２ O-, or a bond; Each R ６ are independently H or C １ -C ８ is a hydrocarbyl; R ８ and R １０ are each independently H, C １ -C ２４ Hydrocarbyl or C containing O or S １ -C ２４ is heterohydrocarbyl; R ９ and R １１ are each independently １ -C ２４ Hydrocarbyl or C containing O or S １ -C ２４ is heterohydrocarbyl; A ９ is C １ -C ８ is a hydrocarbylene or bond; A １０ and A １１ are each independently １ -C ８ is a hydrocarbyl; A １３ and A １４ are each independently １ -C ８ Hydrocarbylene, C １ -C ８ heterohydrocarbylene, or a bond; Preferably, the hydrocarbyl is alkyl, alkenyl, or alkynyl; Preferably, the hydrocarbylene is an alkylene, alkenylene, or alkynylene; Preferably, the heterohydrocarbyl is a heteroalkyl, heteroalkenyl, or heteroalkynyl; Preferably, the heterohydrocarbylene is a heteroalkylene, heteroalkenylene, or heteroalkynylene.

2. 2. The amino lipid compound of claim 1, having a structure represented by formula (II-VIa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 【Chemistry 2】

3. 2. The amino lipid compound of claim 1, having a structure represented by formula (II-IVa), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 【Chemistry 3】

4. 2. The amino lipid compound of claim 1, having a structure represented by formula (II-VIa-c), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. 【Chemistry 4】

5. Y １ Ga-Z ３ C(=O)Z ４ - or -N(R ５ 3. The amino lipid compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

6. Y １ -N (R ６ )C(=O)O-, -OC(=O)N(R ６ 6. The amino lipid compound of any one of claims 1, 2, and 5, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein the amino lipid compound is -OC(=O)O-, or -OC(=O)O-.

7. Y １ 7. The amino lipid compound of any one of claims 1, 2, 5, and 6, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

8. Y １ 7. The amino lipid compound of any one of claims 1, 2, 5, and 6, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

9. Y １ The amino lipid compound or a pharmaceutically acceptable salt thereof according to any one of claims 1, 2, 5, and 6, wherein is -OC(=O)N(H)-, or a stereoisomer thereof.

10. Y １ -N (R ５ 6. The amino lipid compound of any one of claims 1, 2, and 5, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

11. Y １ -N(C(=O)A ９ Office Automation １０ 11. The amino lipid compound of any one of claims 1, 2, 5, and 10, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

12. Y １ -N(C(=O)A １０ 11. The amino lipid compound of any one of claims 1, 2, 5, and 10, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

13. Z １ and Z ２ are each independently -C(=O)O- or -OC(=O)-, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

14. Z １ The amino lipid compound or a pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 5 to 13, wherein is -C(=O)O-, or a stereoisomer thereof.

15. Z １ The amino lipid compound or a pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 5 to 13, wherein is -OC(=O)-, or a stereoisomer thereof.

16. Z ２ The amino lipid compound or a pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 5 to 13, wherein is -C(=O)O-, or a stereoisomer thereof.

17. Z ２ The amino lipid compound according to any one of claims 1, 2, and 5 to 13, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

18. Z １ and Z ２ 17. The amino lipid compound of any one of claims 1, 2, 5 to 14, and 16, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

19. Z １ and Z ２ 18. The amino lipid compound according to any one of claims 1, 2, 5 to 13, 15, and 17, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

20. Z １ is —C(═O)O—, and Z ２ 18. The amino lipid compound according to any one of claims 1, 2, 5 to 14, and 17, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

21. R １ -C(R ６ ) (OR ９ ) ２ 21. The amino lipid compound according to any one of claims 1, 2, and 5 to 20, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

22. R １ -C(H)(OR ９ ) ２ 22. The amino lipid compound according to any one of claims 1, 2, and 5 to 21, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

23. R ２ -C(R ６ ) (OR １１ ) ２ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

24. R ２ -C(H)(OR １１ ) ２ 24. The amino lipid compound according to any one of claims 1, 2, and 5 to 23, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

25. R ２ Z ７ R １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

26. R ２ -C(=O)OR １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

27. R ２ -OC(=O)R １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

28. R ２ Ga-OR １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

29. R ２ -N(H)C(=O)R １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

30. R ２ -C(=O)N(R ６ ) R １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

31. R ２ is substituted C １ -C ２４ 23. The amino lipid compound of any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

32. R １ -C(R ６ ) (OR ９ ) ２ and R ２ -C(R ６ ) (OR １１ ) ２ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

33. R １ -C(H)(OR ９ ) ２ and R ２ -C(H)(OR １１ ) ２ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

34. R １ -C(H)(OR ９ ) ２ and R ２ -C(=O)OR １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

35. R １ -C(H)(OR ９ ) ２ and R ２ -OC(=O)R １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

36. R １ -C(H)(OR ９ ) ２ and R ２ Ga-OR １０ 23. The amino lipid compound according to any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

37. R １ -C(H)(OR ９ ) ２ and R ２ is hydroxyl-substituted C １ -C ２４ 23. The amino lipid compound of any one of claims 1, 2, and 5 to 22, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

38. Y １ is —OC(═O)O—, and R １ -C(H)(OR ９ ) ２ and R ２ -C(=O)OR １０ 38. The amino lipid compound according to any one of claims 1, 2, 5 to 7, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

39. Y １ is —OC(═O)O—, and R １ -C(H)(OR ９ ) ２ and R ２ -OC(=O)R １０ 38. The amino lipid compound according to any one of claims 1, 2, 5 to 7, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

40. Y １ is —OC(═O)O—, and R １ -C(H)(OR ９ ) ２ and R ２ Ga-OR １０ 38. The amino lipid compound according to any one of claims 1, 2, 5 to 7, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

41. Y １ is —OC(═O)O—, and R １ -C(H)(OR ９ ) ２ and R ２ is hydroxyl-substituted C １ -C ２４ 40. The amino lipid compound according to any one of claims 1, 2, 5 to 7, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

42. Y １ is -OC(=O)O-, and A ７ and A ８ is unsubstituted C １ -C ５ alkylene, and R １ -C(H)(OR ９ ) ２ and R ２ -C(=O)OR １０ 38. The amino lipid compound according to any one of claims 1, 2, 5 to 7, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

43. Y １ is -OC(=O)O-, and A ７ and A ８ is unsubstituted C １ -C ５ alkylene, and R １ -C(H)(OR ９ ) ２ and R ２ -OC(=O)R １０ 38. The amino lipid compound according to any one of claims 1, 2, 5 to 7, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

44. Y １ is —N(H)C(═O)O—, and R １ -C(H)(OR ９ ) ２ and R ２ -C(H)(OR １１ ) ２ 38. The amino lipid compound according to any one of claims 1, 2, 5, 6, 8, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

45. Y １ is —OC(═O)N(H)—, and R １ -C(H)(OR ９ ) ２ and R ２ -C(H)(OR １１ ) ２ 38. The amino lipid compound according to any one of claims 1, 2, 5, 6, 9, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

46. Y １ -N(C(=O)A ９ Office Automation １０ )- and R １ -C(H)(OR ９ ) ２ and R ２ -C(H)(OR １１ ) ２ 38. The amino lipid compound according to any one of claims 1, 2, 5, 6, 11, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

47. Y １ -N(C(=O)A １０ )- and R １ -C(H)(OR ９ ) ２ and R ２ -C(H)(OR １１ ) ２ 38. The amino lipid compound according to any one of claims 1, 2, 5, 6, 12, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

48. Y １ -N(C(=O)A １０ )- and R １ -C(H)(OR ９ ) ２ and R ２ is hydroxyl-substituted C １ -C ２４ 38. The amino lipid compound according to any one of claims 1, 2, 5, 6, 12, and 13 to 37, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

49. A ９ is C １ -C ５ 49. The amino lipid compound of any one of claims 1, 2, and 5 to 48, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

50. A １０ is C １ -C ８ 50. The amino lipid compound of any one of claims 1, 2, and 5 to 49, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

51. R １０ is C １ -C ２４ Alkyl, C ２ -C ２４ alkenyl, or C ２ -C ２４ 51. The amino lipid compound of any one of claims 1, 2, and 5 to 50, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkynyl.

52. R １０ is a linear C ２ -C ８ 52. The amino lipid compound of any one of claims 1, 2, and 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

53. R １０ Branch C ７ -C １８ 52. The amino lipid compound of any one of claims 1, 2, and 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

54. R １０ is C ５ -C １２ 52. The amino lipid compound of any one of claims 1, 2, and 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkenyl.

55. R １０ is C ５ -C １２ 52. The amino lipid compound of any one of claims 1, 2, and 5 to 51, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkynyl.

56. R ９ is C １０ C of alkynyl etc. ９ -C １１ 56. The amino lipid compound of any one of claims 1, 2, and 5 to 55, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkynyl.

57. R １４ is C １ -C ５ 57. The amino lipid compound of any one of claims 1, 2, and 5 to 56, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

58. R １４ C has one double bond ４ -C ８ 57. The amino lipid compound of any one of claims 1, 2, and 5 to 56, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkenyl.

59. A １２ is C ２ -C ３ 4. The amino lipid compound of claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

60. A １２ But C １ -C ３ Alkylene (e.g., C １ alkylene), and A ５ and A ６ are each independently, C ３ -C ９ Alkylene (e.g., C ４ -C ９ Alkylene, C ５ -C ９ Alkylene, C ６ Alkylene, C ７ Alkylene, C ８ 4. The amino lipid compound of claim 1, wherein R is an alkylene group, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

61. Z １ and Z ２ are each independently —C(═O)O—, —OC(═O)—, —O—, —C(═O)—, —C(═O)N(R ６ ) -, -N(R ６ )C(=O)-,-N(R ６ )C(=O)O-, -OC(=O)N(R ６ ) -, -N(R ６ )C(=O)N(R ６ )-, -C(=O)S-, -SC(=O)-, -OC(=O)O-, -OC(=O)S-, -SC(=O)O-, -SC(=O)S-, -OS(=O)O-, -OS(=O) ２ 5. The amino lipid compound according to any one of claims 1, 3, and 4, or a pharmaceutically acceptable salt thereof, wherein the amino lipid compound is O-, -OP(=O)O-, -OP(=O)(OH)O-, or -OP(=O)(H)O-, or a stereoisomer thereof.

62. Z １ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

63. Z １ 62. The amino lipid compound or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, according to any one of claims 1, 3, 4, and 59 to 61, wherein: is -OC(=O)-.

64. Z １ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

65. Z １ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

66. Z １ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

67. Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

68. Z ２ 62. The amino lipid compound or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, according to any one of claims 1, 3, 4, and 59 to 61, wherein: is -OC(=O)-.

69. Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

70. Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

71. Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

72. Z １ and Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

73. Z １ and Z ２ 62. The amino lipid compound or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, according to any one of claims 1, 3, 4, and 59 to 61, wherein: is -OC(=O)-.

74. Z １ and Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

75. Z １ and Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

76. Z １ and Z ２ 62. The amino lipid compound of any one of claims 1, 3, 4, and 59 to 61, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

77. Z １ is —C(═O)O—, and Z ２ 62. The amino lipid compound or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, according to any one of claims 1, 3, 4, and 59 to 61, wherein: is -OC(=O)-.

78. A ４ 78. The amino lipid compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

79. A ５ and A ６ are each independently, C ３ -C １０ 79. The amino lipid compound of any one of claims 1 to 78, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

80. A ７ and A ８ are each independently, C ２ -C ４ Alkylene or C ５ -C １０ 80. The amino lipid compound of any one of claims 1 to 79, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

81. Each R ９ became independent and C ３ -C ９ 81. The amino lipid compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

82. Each R ９ became independent and C ５ -C ８ 81. The amino lipid compound of any one of claims 1 to 80, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkenyl.

83. Each R １１ became independent and C ３ -C ９ 83. The amino lipid compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

84. Each R １１ became independent and C ５ -C ８ 83. The amino lipid compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkenyl.

85. A １ and A ２ The dashed line connecting A and １ and A ３ and 85. The amino lipid compound according to any one of claims 1 to 84, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein there is no dashed line connecting them.

86. A １ and A ２ The dashed line connecting A and B is a bond. １ and A ３ and 85. The amino lipid compound according to any one of claims 1 to 84, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein there is no dashed line connecting the two.

87. A １ and A ３ The dashed line connecting A and B is a bond. １ and A ２ and 85. The amino lipid compound according to any one of claims 1 to 84, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein there is no dashed line connecting the two.

88. A １ and A ２ are each independently, C １ -C ５ Alkyl or C １ -C ５ 88. The amino lipid compound of any one of claims 1 to 87, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

89. A １ and A ２ are each independently, C １ -C ３ 89. The amino lipid compound of any one of claims 1 to 85 and 88, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

90. A １ and A ２ are each independently, C １ -C ２ 90. The amino lipid compound of claim 89, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

91. A ２ is C １ -C ３ 89. The amino lipid compound of claim 88, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

92. A ２ is C １ -C ２ 89. The amino lipid compound of claim 88, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein:

93. A ３ is C １ -C ５ 93. The amino lipid compound of any one of claims 1 to 92, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

94. A ３ is C ２ -C ４ 94. The amino lipid compound of any one of claims 1 to 93, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, which is alkylene.

95. A １ and A ２ The dashed line connecting A and B is a bond. １ and A ３ If there is no dashed line connecting A and １ and A ２ and R are taken together with the nitrogen atom to which they are both attached to form an N-containing 4-, 5-, or 6-membered heterocycle, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

96. A １ and A ３ The dashed line connecting A and B is a bond. １ and A ２ If there is no dashed line connecting A and １ and A ３ and R 1 and R 2 together with the nitrogen atom to which they are both attached form an N-containing 4-, 5-, or 6-membered heterocycle, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

97. 97. The amino lipid compound of any one of claims 1 to 96, wherein the amino lipid compound has one of the following structures: 【Table 1】

98. A lipid nanoparticle comprising the amino lipid compound of any one of claims 1 to 97.

99. The lipid nanoparticle of claim 98, further comprising a biologically active component, preferably wherein the biologically active component is a nucleic acid.

100. 100. A pharmaceutical composition comprising an amino lipid compound of any one of claims 1 to 97 or a lipid nanoparticle of any one of claims 98 and 99, and a pharmaceutically acceptable carrier, diluent, or excipient.

101. 98. Use of an amino lipid compound according to any one of claims 1 to 97 in the manufacture of a vehicle for an active ingredient, comprising: Preferably, the use wherein said active ingredient is a pharmaceutically active ingredient, preferably a nucleic acid.

102. 100. Use of an amino lipid compound according to any one of claims 1 to 97, a lipid nanoparticle according to any one of claims 98 and 99, or a pharmaceutical composition according to claim 100 in the manufacture of a medicament.

103. 102. The use according to claim 101, wherein the medicament is for use in the treatment and / or prevention of a disease, preferably the medicament is for use in gene therapy, protein replacement therapy, antisense therapy, therapy with interfering RNA, or genetic vaccination.

104. The use of any one of claims 101 and 102, wherein the pharmaceutical is a nucleic acid pharmaceutical.

105. Use of the amino lipid compound of any one of claims 1 to 97, the lipid nanoparticle of any one of claims 98 and 99, or the pharmaceutical composition of claim 100 in the manufacture of a pharmaceutical for nucleic acid introduction.

106. the nucleic acid is selected from the group consisting of RNA, antisense oligonucleotides, and DNA; Preferably, the RNA is selected from the group consisting of messenger RNA (mRNA), ribosomal RNA (rRNA), microRNA (miRNA), transfer RNA (tRNA), short interfering RNA (siRNA), small nuclear RNA (snRNA), short hairpin RNA (shRNA), single guide RNA (sgRNA), Cas9 mRNA, or a mixture thereof; Preferably, the DNA is a plasmid. The lipid nanoparticle of claim 105.

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